COVID-19 Questions and Answers (updated daily, Part 2)

I am a trained public health professional. Colleagues and friends frequently ask me questions about COVID-19, so I started this daily Q&A to respond. Hopefully these updates are helpful to you too! [These answers are my own and do not represent any organization I’m affiliated with. PART 1, spanning 3/9/20 through 8/26/20 is online here; I’ve migrated all posts to a new website, covidQandA.org.)

Ran out of space here! All posts (including new ones available at: https://covidQ&A.org)

Q&A for 3/13

#Asymptomatic

Note: No Q&A tomorrow.

Question: Has there been any further research on asymptomatic transmission, especially in conjunction with the new variants?

Answer: It has been a while since we revisited the research on asymptomatic transmission and there has been a lot of research published! CDC’s current best estimate is that: a) 40% of cases are asymptomatic; b) asymptomatic individuals are 75% as likely to transmit infection as symptomatic individuals; and c) 50% of new cases are the result of asymptomatic infection. When it comes to asymptomatic transmission and new variants, we still need more research. Do the new variants cause more asymptomatic and/or pre-symptomatic infection? A different period of infectivity? Currently, we have some evidence indicating that those who are infected with B.1.1.7 (UK variant) are more likely to experience any symptoms (see Q&A of 2/16), which would indicate a lower proportion of asymptomatic infection. The evidence base, however, is too shallow to draw any firm conclusion yet. What is abundantly clear thanks to a substantial and growing evidence-base is that asymptomatic transmission is real, it is an important driver of the pandemic, and to control the pandemic we have to limit asymptomatic transmission (hello, universal masking!). Included herein are a few more details.

• A recent meta-analysis published earlier this year in Annals of Internal Medicine examined results of 61 eligible studies to understand the proportion of cases that remain asymptomatic. Researchers concluded that at least 33% of SARS-CoV-2 infections are asymptomatic.
• Results from modeling asymptomatic infection published earlier this year in JAMA found that “59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms.”
• A recent systematic review published earlier this year in Lancet Microbe found that “Several studies reported similar viral loads at the start of infection among asymptomatic and symptomatic patients infected with SARS-CoV-2; however, most studies demonstrated faster viral clearance in asymptomatic individuals, as also seen in MERS-CoV, suggesting a shorter infectious period but with similar potential transmissibility at the onset of infection.”
• A study of asymptomatic infection in healthcare workers published last year in Clinical Microbiology and Infection found that among healthcare workers who became infected with SARS-CoV-2, those who consistently used N95 respirators and wore eye protection were more likely to be asymptomatically infected, indicating a dose/response relationship to viral exposure and severity of symptoms.

Q&A for 3/12

#Allergic Reaction

Question: What are the ingredients in the vaccines that have been the cause of severe allergic reactions for some people?

Answer: The short answer is that we don’t know what causes severe allergic reaction and scientists are actively researching it. Here’s the longer answer:

• Severe allergic reactions are rare and treatable. According to CDC’s vaccine adverse event reporting system, severe allergic reactions after Pfizer/Moderna vaccination have occurred in 2 to 5 people per every million vaccinated in the country (see JAMA paper). Note: An allergic reaction is considered severe when a person needs to be treated with epinephrine or EpiPen or if the person must go to the hospital. Experts refer to severe allergic reactions as anaphylaxis.
• If you have a known allergy to any ingredient in a COVID vaccine, CDC recommends against receiving that vaccine. CDC’s guidance is here and for a full list of ingredients, see Pfizer, Moderna, and Johnson & Johnson fact sheets. Of special note, if you are allergic to polyethylene glycol (PEG), you should not take Pfizer or Moderna vaccines. And if you are allergic to polysorbate, you should not take the Johnson & Johnson vaccine.
• Scientists hypothesize that PEG may be the culprit. As described in a December 2020 report from Science, the Pfizer and Moderna vaccines use lipid nanoparticles (LNPs) to protect the mRNA; the LNPs are ““PEGylated” — chemically attached to PEG molecules that cover the outside of the particles and increase their stability and life span.” PEG is used in medicines and everyday products like toothpaste and shampoo and were long thought to be biologically inert. However, a growing body of evidence indicates that PEG is actually active. A substantial proportion of people have antibodies to PEG. Those individuals with very high levels of PEG antibodies have experienced severe allergic reactions in other drug trials. PEG allergy is also quite rare.
• The NIH is studying the mechanism of severe allergic reaction. According to clinicaltrials.gov, the NIH is about to begin recruiting 2040 individuals with a history of allergic reaction and 1360 individuals with no history of allergic reaction to participate in a randomized control trial to better understand systemic allergic reaction to both Pfizer and Moderna vaccines. The study is expected to last 17 weeks, so hopefully we can see results in the summer. While these results will get us closer to understanding the mechanism of reaction, more study will be required even after this trial.

Q&A for 3/11:

#Deaths per Population

Question: Yesterday you showed the states with the highest/lowest cases per population. What about deaths per population? Are they the same states?

Answer: CDC’s COVID Data Tracker also shows deaths per 100,000 population by state and territory (Figure 1). I’ve listed below the five states with highest and lowest deaths per population. As you can see, four of the five states with the lowest number of deaths/population are also among yesterday’s list of states with the lowest number of cases/population. Makes sense: fewer cases= fewer deaths. Conversely, among states with the highest number of deaths per population, only one of the five (Rhode Island) also appeared in yesterday’s list of states with the highest number of cases/population. This apparent mismatch could be due to a number of factors influencing risk of death — age, race, comorbidities, health systems, local policies, variant type, and more. My mind immediately leapt to population age distribution.

COVID mortality increases dramatically by age. Because age structure varies by state (e.g. some states have much younger populations than others), we’d expect states with older populations to be more likely to experience more deaths/population. This is why it would be beneficial to adjust for age when comparing across states (for more on age-adjustment, see Q&A of 11/24). For example, I’d hypothesize that Alaska appears on the lowest number of deaths/population list because it has the one of the youngest populations in the country (second only to Utah, which ranks 6th in the lowest deaths list). Of course, age composition doesn’t account for all of the variation. Maine has the oldest population age structure with ~21% of the population age 65+ and median age of 45, yet it has experienced one of the lowest proportions of deaths/population of all the states.

Highest number of deaths per 100,000

1. New Jersey (266 deaths / 100,000)
2. Rhode Island (241 deaths / 100,000)
3. Massachusetts (236 deaths / 100,000)
4. Mississippi (230 deaths / 100,000)
5. Arizona (224 deaths / 100,000)

Lowest number of deaths per 100,000

1. Hawaii (21 deaths / 100,000)
2. Vermont (33 deaths / 100,000)
3. Alaska (41 deaths / 100,000)
4. Maine (53 deaths / 100,000)
5. Oregon (54 deaths / 100,000)

Figure 1. Total COVID Deaths per 100,000 by State/Territory (from CDC)

Q&A for 3/10:

#Cases per Population

Question: Since COVID began, which states have been hit the hardest?

Answer: “Hit the hardest” could mean a variety of things, but for the purpose of this answer, I’m going to define it as cases per every 100,000 people in each state’s population. According to CDC’s COVID Tracker, the five states who have suffered the highest cases/population are (Figure 1):

1. North Dakota (13,190 cases / 100,000)
2. South Dakota (12,841 cases / 100,000)
3. Rhode Island (12,175 cases / 100,000)
4. Utah (11,700 cases / 100,000)
5. Tennessee (11,479 cases / 100,000)

For comparison, the five states who have experienced the lowest cases/population are:

1. Hawaii (1,912 cases / 100,000)
2. Vermont (2,596 cases / 100,000)
3. Maine (3,426 cases/ 100,000)
4. Oregon (3,735 cases / 100,000)
5. Washington (4,540 cases / 100,000)

Figure 1. Total COVID Cases per 100,000 by State/Territory (from CDC)

Q&A for 3/9:

#Vaccination #Quarantine

Question: A friend’s doctor told him that since he is fully vaccinated, his quarantine time post potential exposure can be cut to 5 days, plus test. Is this the new guidance for vaccinated people? If yes, why?

Answer: Your friend’s doctor is off the mark in their quarantine recommendation. CDC’s Interim Public Health Recommendations for Fully Vaccinated People (just published yesterday!) includes guidance on this very issue, stating that fully vaccinated people should “refrain from quarantine and testing following a known exposure if asymptomatic.” Here, “fully vaccinated” means 2+ weeks post-second dose for Pfizer/Moderna or 2+ weeks post-single-dose for Johnson & Johnson. CDC’s recommendations further state that, “Fully vaccinated people who do not quarantine should still monitor for symptoms of COVID-19 for 14 days following an exposure. If they experience symptoms, they should isolate themselves from others, be clinically evaluated for COVID-19, including SARS-CoV-2 testing, if indicated, and inform their health care provider of their vaccination status at the time of presentation to care.” To sum up — as long as the fully vaccinated person remains without symptoms, they can go about their daily life (still following good public health practices like masking). However, because no vaccine is 100% effective, if a fully vaccinated person does experience COVID-like symptoms, they should avoid contact with others, get tested, and consult their doctor.

Finally, a reminder on self-quarantine guidelines for non-vaccinated folks — if you have been exposed and remain without symptoms, according to CDC’s guidelines you can self-quarantine for 5 days, get tested on day 5, and upon receipt of negative results you can discontinue self-quarantine (Q&A of 12/4 further describes).

Q&A for 3/8:

#Mask Mandates

Question: What is the collective response from the scientific community about so many states now lifting their mask mandates?

Answer: You’d be hard pressed to find many (any?) public health experts who support lifting mask mandates at this point in the pandemic. Just yesterday, Dr. Fauci cautioned against lifting COVID mitigation measures during an interview with CBS’s Face the Nation stating, “don’t turn the switch on and off because it really would be risky to have yet again another surge, which we do not want to happen, because we’re plateauing a quite a high level — 60K-70K new infections per day is quite high.”

And just this Friday, CDC’s MMWR published this research article, Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates, which found that implementing mask mandates was associated with reduced SARS-CoV-2 transmission, infections, and deaths, whereas reopening restaurants for on-premises dining was associated with increased transmission, infections, and deaths (Figure 1). The researchers emphasized, “Policies that require universal mask use and restrict any on-premises restaurant dining are important components of a comprehensive strategy to reduce exposure to and transmission of SARS-CoV-2. Such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

Figure 1. Mask Mandates Slowed Cases and Deaths (from CDC)

Q&A for 3/5:

#Variant #Disease Severity #B.1.1.7

Note: No Q&A tomorrow. Back at it on Monday!

Question: I was just reading that the B.1.1.7 variant (UK variant) has “grown to account for more than 20 percent of new U.S. cases as of this week.” I know it’s far more transmissible, but is it also more deadly?

Answer: As the New York Times reported earlier today, the share of US cases attributable to the B.1.1.7 variant has grown exponentially (Figure 1). Unfortunately, evidence is accumulating that the variant is not only more transmissible, but is also associated with increased disease severity, including death. We last discussed the disease severity issue in our Q&A of 1/5 and since then, we know a lot more. I’ve included a description of a recent study and a research synthesis herein. As always, please keep masking, distancing, washing hands, and avoiding the 3Cs of closed spaces, crowded places, and close-contact settings. These behaviors work to keep us all safe. And when it’s your turn, please get vaccinated.

• This preprint (not yet peer reviewed) study posted four days ago, Increased Risk of Hospitalisation Associated with Infection with SARS-CoV-2 Lineage B.1.1.7 in Denmark, examined hospitalization rates among individuals in Denmark who tested positive for COVID between 1st January and 9th February 2021. Because Denmark’s genomic sequencing is widespread, researchers were able to split their observational cohort into two groups: a) those with the variant; and b) those without the variant. Controlling for age, sex, region, comorbidities, and several other factors, researchers found that those who were infected with the B.1.1.7 variant had 1.64x higher odds of hospital admission (95% confidence interval 1.32–2.04).
• The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), a government advisory group to the UK presented a synthesis of evidence on 1/21, which it updated with new evidence (~1 dozen studies) on 2/11. For example, one study included in the update was from the London School of Hygiene and Tropical Health, which found the risk of death (relative hazard of death) within 28 days of a positive test to be 1.58x higher for individuals infected with the variant (95%CI 1.40–1.79). Based on its review of current evidence NERVTAG concluded, “it is likely that infection with VOC B.1.1.7 is associated with an increased risk of hospitalisation and death compared to infection with non-VOC viruses.”

Figure 1. Growth of B.1.1.7 Variant Cases in the US (from NY Times)

Q&A for 3/5:

#Vaccine #Dose #Protection

Question: My wife’s school district is trying to get her to go back 3 weeks after her first Pfizer dose, 1 week before her second dose. What is the protection she will have first going back?

Answer: In good news, she will have a good deal of protection 3+ weeks after her first dose; her risk of infection will be reduced by an estimated 60%. Of course, the protection afforded 7+ days after the second dose will be even stronger; her risk of infection will be reduced by an estimated 92%. Read on for the details.

We talked about Pfizer vaccine efficacy after the first dose in our Q&A of 1/23, but since then, we have more real-world evidence. As I wrote in late January, the Pfizer clinical trial data published in the New England Journal of Medicine (NEJM), shows that the Pfizer vaccine efficacy in the interval between first and second dose is 52% (range: 30% to 68%). More recently, NEJM published an analysis of real-world vaccine effectiveness from Israel, BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. Researchers compared infection and disease outcomes between vaccinated and unvaccinated individuals. Using data from a study group of nearly 1.2 million individuals, researchers calculated vaccine effectiveness 14–20 days and 21–27 days after the first dose and 7+ days after the second dose (Table 1). As you can see in Table 1, protection afforded after the first dose as documented in real world settings is quite similar to that documented in the clinical trial, and is relatively high (though not nearly as high as effectiveness after the 2nd dose). And in case you want a reminder of what the terms “vaccine efficacy” and “vaccine effectiveness” mean, check out our Q&A of 2/19 and/or this recent NY Times article, What Do Vaccine Efficacy Numbers Actually Mean?, which also offers some great visualizations.

Table 1. Pfizer Vaccine Effectiveness (from NEJM paper)

Q&A for 3/4:

#Excess Deaths

Question: How many deaths did the US experience in 2020 and how does it compare with previous years?

Answer: We’ve talked about excess deaths in previous posts (see Q&A of 8/24), but it’s been many months since we’ve revisited the topic. Using data from CDC, I pulled together a simple table to show how total deaths have changed year-to-year since 2015 (Table 1). Deaths counts from 2020 are still not finalized, but as you’ll see from these provisional numbers, the United States experienced 3,358,549 deaths in 2020, which is 506,224 more deaths than experienced in 2019 (an 18% increase). According to CDC’s estimates, at least 377,650 deaths last year involved COVID-19. At least 555,996 deaths involved either COVID, pneumonia, or influenza.

Table 1. Yearly trends in all-cause mortality in the USA (2015–2020)

Q&A for 3/3:

#Vaccine Trials #Africa

Question: Which vaccines have clinical trials on the African continent?

Answer: At least seven (7) COVID vaccines have clinical trials in Africa (Table 1) and they [have been/are being/will be] tested in three African countries — Egypt, Morocco, and South Africa. Read on for a bit more background.

African countries are oftentimes neglected in vaccine research. According to the African Academy of Sciences, only 2% of clinical trials globally, for all types of vaccines, take place on the continent. To counter this problem, in late June 2020, the African Union announced a new consortium of vaccine developers, funders, and scientific organizations, the Africa CDC Consortium for COVID-19 Vaccine Clinical Trial (CONCVACT). CONCVACT aims to ensure that at least 6 late-stage COVID-19 vaccine trials are completed in Africa. The Consortium is also working to improve regulatory approval and roll-out processes post-trial and to foster Africa-based manufacturing capacity. When the Consortium was announced, only two of 33 trials were being conducted on the continent. Since then, the number of trials has increased. If you’d like to read more, here are three excellent sources:

1. Lancet Respiratory Health, COVID-19 vaccine trials in Africa (September 2020);
2. Health Affairs, A Case For More (And More Ethical) COVID-19 Vaccine Trials In Africa (January 2021); and
3. Lancet Global Health, An interactive website tracking COVID-19 vaccine development (March 2021).

Table 1. COVID Vaccination Clinical Trials in Africa (data from Vaccine Tracker, Novavax Press Release, and Science Magazine)

Q&A for 3/2:

#Vaccine Timeline #Production

Question: At the House Commerce Committee hearing last week, the President of Pfizer said they intended to ramp up production with an additional 140 million vaccines in the next five weeks. By my math (and I’m a lawyer, not a mathematician), that is an additional 4 million vaccines a day! Considering we’ve averaged under 1.5 million vaccines a day, that number seems really high. Why is this not bigger news? Is their statement credible?

Answer: Thanks for raising this question, which prompted me to read through the written testimonies shared at last week’s House Energy and Commerce hearing. I’ve provided a few highlights from the testimonies in the below bullets. I have seen this ramp-up discussed in some news outlets (e.g. CBS, Washington Post, Axios, Biopharm), though it hasn’t been front-page news. Among other reasons, I suspect it’s not making bigger waves because: a) people will believe it when they see it; b) people are already expecting vaccine production to ramp-up; and c) increasing the number of doses manufactured is necessary but not sufficient for increasing the pace of vaccines administered. As President Biden said when he toured Pfizer’s vaccine facility last month, “It’s one thing to have the vaccine, and it’s very different to get it in someone’s arms.” With this in mind, the Administration is working to overcome vaccine hesitancy and increase demand for vaccines while also supporting expanded access to vaccines through pharmacies, community health centers, mass vaccination sites, and more. According to MarketWatch,the National Association of Chain Drug Stores estimates its members alone have the capability to deliver >3 million doses/day. And as you’ll see in the bullets below, the US should be flush with doses very soon!

Hearing Highlights (bold font is mine) [I’ve only included bullets for the three vaccines that have FDA authorization. You can find testimonies for Novovax and AstraZeneca here and here]

• John Young, Chief Business Officer, Pfizer: “We expect to increase the number of doses we make available for shipment from approximately 4 to 5 million doses per week at the beginning of February to more than 13 million doses per week by the middle of March. We are on track to make 120 million doses available for shipment by the end of March and an additional 80 million doses by the end of May. And, we anticipate all 300 million contracted doses will be made available for shipment by the end of July, enabling the vaccination of up to 150 million Americans…. This is possible because Pfizer has made significant investments in our U.S. manufacturing sites…”
• Dr. Stephen Hoge, President, Moderna: “We are on track to meet our commitment to deliver 100 million doses by the end of March. We have doubled our monthly deliveries since late 2020, and we are aiming to double them again by April to more than 40 million doses per month. Based on this progress scaling up manufacturing, we recently agreed to move up our delivery timeline: we now are aiming to deliver a second hundred million doses by the end of May and a third hundred million doses by the end of July… We are able to accelerate these delivery timelines — while maintaining a robust commitment to safety and quality — thanks to the highly-skilled and experienced workers at our Massachusetts facility, our raw material suppliers, our contract manufacturing partner Lonza, and our fill-finish contractor Catalent… we are pursuing a plan that may allow up to 15 doses to be drawn from each vial. This will allow us to produce and deliver more doses more quickly.”
• Dr. Richard Nettles, Vice President of U.S. Medical Affairs, Johnson & Johnson: .”.our plan is to begin shipping immediately upon emergency use authorization, and deliver enough single-doses by the end of March to enable the vaccination of more than 20 million Americans. We are confident in our plans to deliver 100 million single-dose vaccines to the United States during the first half of 2021… Our goal is to have seven COVID-19 vaccine manufacturing sites active by midyear.”

Q&A for 3/1:

#Testing #Anal Swabs

Question: Are anal swabs better at detecting COVID-19 than nasal swabs?

Answer: Anal swabs have been in the news quite a bit in the past week or so with the revelation that the Government of China subjected US diplomats to anal swab tests for COVID-19. This news follows reporting from Fobes and Reuters from late January 2021 that China had begun to use the tests for high-risk individuals, including passengers arriving to Beijing and individuals in quarantine. Anal swab tests include the insertion of a cotton-tipped swab 1–2 inches into the rectum to collect a sample for PCR testing. The tests are clearly far more invasive than nasal and throat swabs. Based on the evidence I’ve read (further described herein), unless the testing involves very young children, anal swabs are not meaningfully better at detecting active infection.

• The virus is detectable in stool for a longer period than in nasal/throat cultures, but this finding is not necessarily clinically meaningful. Evidence from a pooled analysis of 8 cohort studies indicates and a systematic review of 95 studies found that the virus is detectable for a longer period of time in stool samples compared with nasal/throat samples. However, just because anal swabs are better able to find viral particles does not mean that they are better able to find active infections. A longer duration of viral shedding in the gastro-intestinal tract does not necessarily equate to a longer-duration of infectivity. In fact, available data show that clinically recovered adults with prolonged viral shedding have not transmitted SARS-Cov-2 to others. As a result, CDC does not recommend using a testing-based strategy to end isolation (except among severely immunocompromised patients) because viral shedding can last much longer than infectivity and sickness.
• Anal swab testing may be worthwhile if a young child presents with COVID-19 symptoms/exposure, but tests negative from nasal/throat swab. Based on their experience treating an infant, the doctors who authored this case study concluded, “Physicians should be aware that asymptomatic or mildly ill children with history of exposure and negative pharyngeal/nasal swabs and positive anal swabs are potential sources of infection via fecal–oral transmission for COVID-19. In addition to nasal/pharyngeal swabs, we believe that children should be tested for SARS-CoV-2 using anal swabs.”
• Fecal/oral transmission remains a theoretical concern. Because SARS-CoV-2 can be present in stool, the role of fecal/oral transmission is a possibility. This is yet another reason that good hand washing behavior is so important!

Q&A for 2/27:

#Vaccines #Children

Note: No Q&A tomorrow. Send questions along if you have them.

Question: Do you know how we can enroll our daughter in a COVID vaccine trial? She’s 5 now, and I understand that Pfizer, Moderna and J&J all need to be tested on kids before they can be approved for kids.

Answer: Because children’s immune systems differ from adult’s systems, it’s especially important to have rigorous safety and efficacy evaluation among children (see Q&A of 12/9). Generally, after safety/efficacy has been proven for adults, trials expand to include older children. As safety, efficacy, and dosing is proven for older children, studies enroll younger children. Moderna and Pfizer have fully enrolled their current pediatric trials, which include children ages 12+. Data are expected later this Spring, at which point younger children will be enrolled in the study. AstraZeneca started its vaccine trial of children ages 6+ in the UK earlier this month. And Johnson & Johnson is expected to begin enrolling children soon. All that to say, there’s not yet the opportunity for your daughter to be enrolled in a COVID vaccine trial in the United States. To keep tabs on opportunities, the best place to look (to my knowledge) is clinicaltrials.gov. The next best place to look is the vaccine developer’s websites themselves: AstraZeneca, Johnson & Johnson, Moderna, Novovax, and Pfizer. Finally, it’s always good to talk with your pediatrician, who can also likely identify potential opportunities.

Q&A for 2/26:

#Steroids #Safety

Question: Is it safe to have the Covid vaccine while using topical steroids?

Answer: I’m not a medical doctor and this is a question best answered by a medical doctor. Please consult your doctor! With that nudge, I’ll share what I know based on what I’ve read. First off, a lot depends on how long you’ve been taking the corticosteroid and what the dosage is. If it’s a low/moderate dose taken for less than 2 weeks, I don’t think there’s anything to be concerned about. If, however, it’s a moderate/high dose* that you’ve taken for 14 days or more, there are a few concerns:

• Corticosteroids have the potential to be immunosuppressive and are presumed to cause some degree of altered immunocompetence. Having a compromised immune system means that the effect of vaccination may not be as robust. In this case, it’s best to talk with your doctor about whether to continue taking the steroids and have the jab OR discontinue use of the steroid for a bit of time then take the vaccine for improved immune response. There are pros/cons of each approach.
• The second issue concerns safety. For inactivated vaccines there’s no safety risk associated with taking corticosteroids when vaccinated. However, for live attenuated vaccines (like MMR, Yellow Fever), many clinicians consider relatively high doses* of steroids taken for ≥14 consecutive days to be sufficiently immunosuppressive to warrant concern about the safety of vaccination. For live attenuated vaccine administration, the Advisory Committee on Immunization Practices (ACIP) recommends, “Vaccination providers should defer live-virus vaccination for at least 1 month after discontinuation of high-dose systemically absorbed corticosteroid therapy administered for ≥14 days.” Here it’s important to note that all COVID vaccines currently authorized for use or under consideration (e.g. Pfizer, Moderna, Johnson & Johnson) are inactivated (for a reminder on vaccine types, see Q&A of 1/21). This means that the safety concerns described herein do not currently pertain to COVID vaccinations.
• Finally, CDC’s clinical guidance for mRNA vaccines against COVID states, “Immunocompromised individuals can receive COVID-19 vaccination if they have no contraindications to vaccination [e.g. severe allergic reaction]. However, they should be counseled about the unknown vaccine safety profile and effectiveness in immunocompromised populations, and the potential for reduced immune responses…”

*Per ACIP and PAHO, “many clinicians consider a dose equivalent to either 2 mg/kg of body weight or a total of 20 mg per day of prednisone for 2 or more weeks as sufficiently immunosuppressive to raise concern about the safety of vaccination with live virus vaccines.”

Q&A for 2/25:

#Vaccination Availability

Question: Is there an easy way to find local vaccine availability and sign up for an appointment?

Answer: The federal government did not create a centralized site for vaccine sign-up. As a result, states, localities, hospital systems, pharmacy chains, and more have developed their own vaccination sign-up systems. It’s a patchwork approach that puts the onus on individuals to navigate, oftentimes by signing up through multiple different systems that do not communicate with one another. Yes, it’s confusing and burdensome. As Claire Hannan, who runs the Association of Immunization Managers recently described to NPR, “I can’t tell you how complicated it is to have a federally financed vaccine being distributed through a state-based system, with a health care system that’s private-sector based. These three things are completely separate and operate in their own kingdoms. So, trying to marry all of this and to track it in real time with data connections? It’s incredible that we are where we are.” Recognizing the complications, here are a few tools to help navigate the process:

1. NPR’s Tool can direct you to relevant links for your state, including links to local information on who is currently eligible, central state registration site (if available), local providers, and local resources.
2. VaccineFinder.org allows people to enter their zip code and the distance they are willing to travel to show vaccine availability by location with relevant links to sign up. The NY Times published an informative article yesterday about the effort, Helping People Find Covid-19 Vaccines Is Aim of C.D.C.-Backed Site.
3. CDC’s Pharmacy Providers List provides a state-by-state description of which pharmacies and retail chains are participating in the federal vaccine program. You can use this list to know which retail pharmacies you can register with in your locale.

Q&A for 2/24:

#Vaccination #Infection Risk

Question: In a household of two 60-something partners, one gets the vaccine and the other doesn’t. How could that work, what should be their protocols for the unvaccinated one?

Answer: If one person in the household is vaccinated and the other is not then the focus needs to be on keeping the unvaccinated partner safe. Until we know more about whether vaccinated individuals can become infected and transmit the virus to others, partner behaviours shouldn’t change much from what they were doing pre-vaccination (see Q&A of 2/7). Both partners should continue following good public health practices, including masking, distancing, and hand washing. Meanwhile, the vaccinated partner could take on more of the household responsibilities that are associated with increased risk — any responsibility associated with crowded places, closed spaces, close-contact settings — in order to limit the unvaccinated partner’s potential exposures. In good news, evidence has been building over the last few weeks, which indicates that the Pfizer vaccine greatly reduces infection and onward transmission risk (see Q&A of 2/18). For example, on Monday Public Health England announced that data from its Siren Study of healthcare workers <65 years old show that the vaccine “provides high levels of protection against infection” — 70% after the first dose rising to 85% after the second dose. At this point, we don’t have enough information to draw firm conclusions, but the initial signs are extremely positive! Until we have enough evidence, please keep up with good public health practices whether you’re vaccinated or not.

If you’d like to read more on the topic, this article published yesterday in the Washington Post provides a nice synthesis.

Q&A for 2/23:

#Dose Timing

Question: I was reading that the longer spacing between first and second doses of the AstraZeneca vaccine (12 weeks vs. 6 weeks), the better the immune response. Why would the timing of the second dose matter?

Answer: Here’s a wee bit of background, hypotheses, and a finally, a more direct answer to your question.

Background. Vaccines work by imitating an infection that causes the immune system to respond by developing B-cells and T-cells that remember how to fight the disease in the future. This immunological memory is the basis of long-term protection. To use an analogy, when we’re learning something new, one lesson often doesn’t cut it; we need refresher training to make sure that the lesson sticks. So it goes with our immune system’s memory — sometimes it takes more than one lesson for your immune system to fully learn and remember how to respond, hence the need for a booster shot. For quick refresh on how the immune system works, see Q&A of 5/9.

Hypotheses. Because our immune systems are complicated and there’s still a lot that we are learning, we still don’t know what the optimal time for boosting is and whether it varies based on vaccination-type. Some evidence suggests that an interval of at least 2–3 months between the prime and the boost is necessary for optimal immune response. Meanwhile, evidence from computational simulations indicates that an interval of “several weeks between the prime and the boost is necessary to obtain optimal responses… efficiency increases when the second dose is given 45 to 90 days after the prime whereas further delaying the boost does not improve the secondary antibody peak.” The hypothesized reason for the importance of a boosting interval is that the memory T cells take several weeks to form after the first shot, and memory B cells have to go through a germinal center (lymph nodes and spleen) maturation process that can take several months. Scientists also hypothesize that the innate immune system may contribute to the boosting effect of the second dose if enough time is given for special innate system cells to develop.

Answer. To ensure that your immune system has fully learned the lesson and is ready, willing, and able to respond when it encounters the real virus, it would benefit to wait to give the second dose until the memory T cells and B cells have developed, and the innate immune system is primed. This requires an interval of at least 3–4 weeks, but evidence from various studies indicates that an interval of 2–3 months may be superior.

Q&A for 2/22:

#FDA Authorization #Vaccines

Question: When can we expect FDA approval for other vaccines?

Answer: The FDA is currently reviewing documentation provided by Johnson & Johnson for its 1 dose vaccine, which is a viral vector-type (for a refresh on vaccine types, see Q&A for 1/21). The FDA’s Vaccines Advisory Committee will meet later this week (Friday, 2/26) to discuss. FDA’s determination for/against emergency use authorization should come very soon after that meeting. We could have a third vaccine authorized for use within a week’s time! The US expects to have 100 million doses by June, although there are only a few million doses in the J&J inventory to start.

The next vaccine likely to undergo FDA review is AstraZeneca’s 2-dose viral vector-type vaccine. Though the vaccine is already authorized for use by the WHO and other non-US institutions, the FDA is waiting to review data from the large, US-based clinical trial. These data will likely be available later in March, which would push the timeline for FDA authorization likely to April. The US has an agreement with AstraZeneca to secure 300 million doses, though I’m not sure how many doses/week would be available for distribution based on manufacturing capacity and global demand.

Of course, many more vaccine candidates are in development. According to WHO’s vaccine landscape analysis updated earlier today, 17 additional vaccine candidates are currently in Phase 3 or 2/3 clinical trials. One of these is Novovax’s 2-dose protein subunit-type vaccine, which is currently being studied in the US, Mexico, and the UK. Just earlier today, Novovax reported that it had completed enrollment for its trial in the US. If all goes well, the US could have 110 million doses of the Novovax vaccine by June.

Q&A for 2/21:

#Herd Immunity

Question: I was reading an opinion piece in the Wall Street Journal that we could reach herd immunity by April. Do you think that’s realistic?

Answer: The author, a medical doctor and professor at Johns Hopkins, argues that we’re witnessing this big drop in daily cases because so many people have already been infected; because we are quickly approaching herd immunity. I have doubts about this assessment, which I’ve synthesized below. For a refresh on the concept of herd immunity, check out our Q&A of 5/1. And to examine different herd immunity scenarios, check out this article and set of data visualizations the New York Times published yesterday, When Could the United States Reach Herd Immunity? It’s Complicated. My hope is that we will continue to ramp up vaccine distribution and administration and my current optimistic expectation is that we will achieve herd immunity by the end of the summer.

1. The author doesn’t seem to take into account human behavior. As cases spiked earlier last month and details emerged about new virus variants, we would have expected people to modify their behavior to reduce their risk, which in turn would have reduced the scope of community transmission. More people wearing masks, more people double masking, fewer people traveling, fewer people attending large gatherings — these changes in behavior can have sweeping changes in the trajectory of the pandemic. For example, let’s turn to our experience of previous waves. Remember the first terrible wave that hit New York (Figure 1)? Cases, hospitalizations, and deaths dramatically declined after mid-April, but the state was nowhere near herd immunity. Indeed, serology testing soon after the first wave in New York City (a big hotspot) revealed that only 21% of city residents had been infected. The end of the first wave was not due to herd immunity, it was because people and communities dramatically changed their behavior and New York was able to curb community transmission for many months.
2. The author rests his hypothesis on a mathematical guess that cannot be tested. The author posits that 55% of us have been infected with the virus, estimating that the ~28 million confirmed cases in the country represent only 10%-25% of all cases because of both asymptomatic transmission and limited testing. He then goes on to describe why antibody testing cannot capture the full extent of all cases. It is true that testing has not captured all cases and antibody tests are limited, but to make such a sweeping guess that 55% of us have already been infected without having solid evidence to back it up is suspect.
3. The author lets other hypotheses go unaddressed: In addition to the human behavior element I described above, other experts suggest the declining case rates could be due to increasing vaccination rates, to the changing seasons, or even to undertesting.

Figure 1. Trends in Covid Cases, Hospitalizations, Deaths in New York State (data from covidtracking.com)

Q&A for 2/20:

#Vaccine Prioritization #Prisons

Question: I just read this article about LA and the issue of social distancing in a crowded household. It made me think of whether any of the vaccine efforts should or have prioritized those in living situations that are hard to social distance, such as these, and nursing homes, prisons, etc. I have mostly seen age (b/c of severity) and health care works/teachers (understandably), but from a public health perspective, should we also be prioritizing places that are harder to social distance? and/or have other vaccine roll out plans (even in other countries) prioritized it in this way?

Answer: Prioritization of scarce, lifesaving resources is full of ethical dilemmas. We know that those individuals living and working in congregate settings are at increased risk of contracting COVID — we’ve seen it in nursing homes, prisons, meatpacking plants, crowded households, and more. Some of these individuals — those living in nursing homes and those essential workers like meatpackers — have been consistently prioritized by key groups like the Advisory Council on Immunization Practices (ACIP). However, because vaccine prioritization policy is state-led, there are numerous, varying policies being enacted across the country. A recent NY Times article, Where Do Vaccine Doses Go, and Who Gets Them? The Algorithms Decide, offers a helpful summary of some of the complexity. For example, Tennessee has developed vaccine prioritization algorithms using variables like poverty and crowded housing to identify neighborhoods that would receive extra doses to facilitate faster vaccination.

When it comes to incarcerated individuals, the variation in vaccination policy by state is striking. The Prison Policy Initiative offers a thorough overview of the issue — “COVID-19 case rate is four times higher in state and federal prisons than in the general population — and twice as deadly. And despite the danger of close quarters and high rates of preexisting health conditions among incarcerated people, prisons and jails have widely failed to reduce their populations enough to prevent the spread of the virus… The federal Bureau of Prisons announced in November that it plans to reserve its early allotments of the vaccinations for staff, not incarcerated people…” The Initiative also keeps an updated chart of incarcerated population vaccination policy by state (Table 1). As you can see from the table, there are 9 states who include incarcerated people in Phase 1 vaccination plans and there are 9 states who do not include incarcerated people in any Phase. The American Medical Association recommends compassionate release policies among other measures to ethically care for those living in jails and prisons, particularly in the face of the pandemic. And CDC recommends that incarcerated people and corrections staff receive vaccination at the same time because of their shared risk.

Table 1. State-level vaccination prioritization for incarcerated people and corrections staff (from Prison Policy Initiative)

Q&A for 2/19:

#Vaccine Efficacy

Question: We keep talking about vaccine efficacy. I thought 95% efficacy meant that 95 of 100 people vaccinated would be protected. Is that correct?

Answer: That’s what a lot of us think vaccine efficacy means, but alas, it’s incorrect. Instead of thinking about vaccine efficacy in terms of “people protected,” we should think about it in terms of “risk reduction.” Pfizer had 95% efficacy and Moderna had 94% efficacy in clinical trials. This means that the two vaccines reduced the vaccinated population’s risk of becoming sick with COVID by 95% and 94% respectively.

Two days ago, Lancet published a short comment on this very topic, What does 95% COVID-19 vaccine efficacy really mean?. As the author describes, if we estimate that the virus has an attack rate of 1% over a 3 month period, a non-vaccinated population would expect to experience 1,000 COVID cases per every 100,000 individuals. If that population were vaccinated with a 95% effective vaccine, we would expect a 95% reduction in the risk of disease; instead of 1,000 cases/100,000 individuals over 3 months, we would expect 50 cases/100,000 individuals over 3 months.

A quick note on vaccine efficacy vs. effectiveness: Vaccine efficacy is a measure of how well the vaccine performs in clinical settings. Meanwhile, vaccine effectiveness is a measure of how well the vaccine prevents disease in “real world” settings, e.g. outside of clinical trials. The data from Israel shared in yesterday’s Q&A was vaccine effectiveness; preliminary analytic results show Pfizer’s vaccine effectiveness (94%) is nearly equivalent to its efficacy (95%).

Q&A for 2/18:

#Vaccine #Transmission

Question: How much, if any, confidence can we have in these new Israeli studies on the Pfizer vaccine, which show that the vaccine may reduce transmission?

Answer: As of early February, nearly 90% of Israelis age 60+ had received their first dose of Pfizer and more than 40% of Israelis had been vaccinated with at least the first dose. With relatively quick vaccine roll-out plus robust data collection, Israel offers unique insights. Here are three recent take-aways:

1. Pfizer’s real-world effectiveness is similar to clinical trial efficacy. Last week, Israel’s largest healthcare provider, Clalit, reported a 94% drop in symptomatic COVID-19 infections among the 600,000 people who received two doses of the Pfizer’s vaccine as compared with 528,000 individuals who did not receive any vaccination, controlling for a host of background factors. This finding is quite stunning — real-world effectiveness is mirroring clinical trial efficacy. Based on what was reported from Clalit in the news, the study sounds quite robust and the findings do align with what we saw in the clinical trial. Unfortunately, the findings are preliminary and I have not been able to locate any pre-publication report. To answer your question, I think you can put a good degree of faith in the findings, but I wouldn’t be 100% confident (high threshold) until we actually have the report in hand and it has been peer-reviewed.
2. First dose of Pfizer decreases SARS-CoV-2 viral load. A new pre-print publication (not yet peer reviewed) from Israel’s Maccabi Healthcare Services shows that those individuals who became infected with SARS-CoV-2 twelve (12) or more days after their first vaccine shot but before their second shot had statistically (and meaningfully) lower viral loads as compared with similar individuals who had not yet received a first shot as well as individuals who became infected within 1–11 days of receiving their first dose. I found this read quite compelling and the study design strong. As with all publications, this one will improve with peer-review, but the overall finding seems to be robust even in light of the limitations the authors outline. This finding is so important because…
3. Lower viral loads likely mean less transmission. Earlier this month, Lancet Infectious Diseases published, Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study, which thoroughly examined why some people seem to be more contagious than others (e.g. risk of transmission). Authors conclude, “the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner.” In essence, higher viral loads were found to lead to more transmission. Higher viral loads were also more likely to result in more symptomatic cases (FIgure 1).

Figure 1. Relationship to Viral Load and Symptomatic Disease (from Lancet)

Q&A for 2/17:

#Antibody Tests

Question: After having had both doses of the Pfizer vaccine, and having given it a couple of weeks to register in my system, would it be a good idea to get an antibody test for proof?

Answer: CDC does *not* recommend antibody testing to assess for immunity after vaccination. A recent Washington Post article provides additional information supporting CDC’s guidance. In short, it seems highly likely that you’ll get a false negative result. Given the strength of the Pfizer (and Moderna) vaccines in clinical trials, you can consider yourself immunized and safe from moderate and severe disease 3 weeks after the second shot. Because we still don’t know whether immunized people can carry the virus and transmit it to others, please keep up with good public health practices even after you’re vaccinated — masking, social distancing, hand washing, avoiding crowded places, close contact settings, and closed spaces. If you’d like to read more, I’ve included a bit more detail on the antibody testing issue in the below paragraph.

Why not get an antibody test?

After vaccination with Pfizer or Moderna, the antibodies formed will be to only one part of the virus — the spike protein. When it comes to COVID antibody tests, there are generally two types — those that detect antibodies to the nucleocapsid protein and those that detect antibodies to the spike protein. Tests that detect nucleocapsid protein antibodies will not pick up any markers of vaccine-derived immunity. Meanwhile, scientists aren’t sure how well spike protein antibody tests will fare at detecting markers of vaccine-derived immunity. Plus, a positive antibody test from such a test cannot differentiate between previous infection and vaccine-derived immunity. Antibody tests are further limited because they only measure one component of immunity (antibodies) but not others (e.g. T-cells). All that to say, antibody tests are likely to give false negative results; even when they give true positive results, you can’t be sure that it’s due to vaccine-derived immunity; and even if they give true negative results, you can’t be sure that it means you aren’t protected against COVID (hello, T-cells).

Q&A for 2/16:

#B.1.1.7 #Symptoms

Question: I read that the UK variant could become the dominant strain in the US in March. Are the symptoms from the UK variant the same as those of the original virus?

Answer: Scientists in the UK have been examining whether symptoms associated with the UK variant (B.1.1.7) differ from those associated with the original virus. I’m aware of two different surveys that are examining this issue — 1) the UK Office of National Statistics COVID-19 Infection Survey and 2) the Imperial College’s REACT survey. Preliminary analyses from both surveys indicate that people who test positive for the B.1.1.7 variant are:

• More likely to experience any symptoms;
• More likely to experience certain symptoms like cough;
• Just as likely to experience gastrointestinal symptoms; and
• Less likely to experience loss of taste or smell.

Figure 1 provides a synthesis of the recent findings from the Office of National Statistics.

Figure 1. B.1.1.7 Symptoms and Original Virus Symptoms (from UK Office of National Statistics COVID-19 Infection Survey)

Q&A for 2/12:

#Vaccination #Dose #Timing

Note: Happy President’s Day Weekend. I’m pausing daily updates for the long weekend until Tuesday, 2/16. In the meantime, please keep sending your questions and I’ll add them to the queue.

Question: I am going on a cross country RV trip in May for 6 weeks. If I get the opportunity to take the first vaccine before I leave but have to wait 6 to 8 weeks for the booster will it still be effective?

Answer: I’m going to focus this answer on the two vaccines currently authorized for use in the US — Pfizer and Moderna. I imagine that by the time May is here and you’re off on your amazing RV adventure, we’ll have a much wider variety of vaccines in distribution and the guidance on dose timing could very well differ by vaccine. For example, AstraZeneca reports improved efficacy with a longer interval between doses (12+ weeks). So back to what we know of Pfizer and Moderna… Ideally, you would be vaccinated according to the clinical trial protocols, which means 21 days after the first dose for Pfizer and 28 days after for Moderna. Of course, we can’t all achieve the ideal. In that case, an interval of 6 weeks should still be okay. I’d recommend against waiting longer than 6 weeks as we have no data on the efficacy of vaccines administered beyond that 6 week window (see CDC clinical guidelines, relevant portion copied below).

We talked about vaccine efficacy after 1 dose in our Q&A of 1/23. Since then, the UK’s vaccination program is reporting that real-world data suggest the Pfizer vaccine is 65% effective after the first dose (findings not yet peer reviewed). This to say, you will have some important protection after the first dose and you should aim to get your second dose as soon as you can within the 3–6 week window.

CDC clinical guidelines
The second dose should be administered as close to the recommended interval as possible. However, if it is not feasible to adhere to the recommended interval and a delay in vaccination is unavoidable, the second dose of Pfizer-BioNTech and Moderna COVID-19 vaccines may be administered up to 6 weeks (42 days) after the first dose. There are currently limited data on efficacy of mRNA COVID-19 vaccines administered beyond this window. If the second dose is administered beyond these intervals, there is no need to restart the series.

Q&A for 2/11:

#Vaccination #Exercise

Question: Our senior family feels so fortunate to get our second jab of Pfizer vaccine next week. We are reading conflicting info in NYTimes and WebMD about aerobic exercise before and after. You dig a good workout, I know. Your thoughts? Should we skip the zoom Pilates/weights the hour after the jab?

Answer: Short answer: I recommend keeping up with your regular exercise routine as long as you feel good.

Longer answer: I was surprised that there was conflicting guidance in this space, so I took some more time to read up. Obviously, we know that being fit and regularly exercising is good for your health. Accumulating evidence also shows that “physical activity promotes a strong immune system and better vaccine responses.” And there’s a whole set of research aimed at understanding whether the timing of exercise — either soon before or soon after vaccination — can reduce pain associated with vaccination, improve antibody response to the vaccine, and/or reduce the occurrence of side effects associated with the vaccine. In my relatively quick skim of related scientific articles in pubmed, I found that there’s nothing that indicates exercise is harmful either pre- or post-vaccination; rather, studies indicate that exercise is either beneficial or has no influence (for example, see here, here, here, and here). Having confirmed my original understanding, I became even more confused why anyone would express any doubts about exercise… so I read a little more. And I think the issue is as follows: because there have been some rare cases of severe allergic reactions after COVID vaccination (CDC estimate is 11.1 cases per million doses of Pfizer vaccine); and because exercise has also been rarely associated with severe allergic reactions; a doctor WebMD interviewed connected these dots and suggested that people avoid exercise after vaccination to reduce possibility of severe allergic reaction. The problem with this advice is that it is an overinterpretation of the evidence to date.

A few more notes: There are recommendations that children with egg allergies who are at high-risk of anaphylaxis (due to egg-based vaccinations like influenza) “should be observed for 60 minutes and restricted from strenuous exercise for one day.” To my knowledge, that’s the only relevant exercise/vaccination recommendation; there have not been cases of exercise induced anaphylaxis associated with the Pfizer or Moderna vaccine; and individuals with a history of severe allergic reaction are precautioned against and in some cases contraindicated for receiving the Pfizer and Moderna vaccines. A well-respected doctor, Dr. Peter Hotez, recently responded to the claim that a person should avoid exercise before getting the jab, affirming that individuals should “Keep up with your regular exercise routine. It’s really important, especially in this time of Covid.”

Q&A for 2/10:

#Vaccination #Pregnancy

Question: The number one question my wife and I are struggling with right now concerns the vaccine (Pfizer one to be specific). I should say, we are STRONG believers in vaccines writ large. She is pregnant and due in late April. She has higher exposure risks than average people (she works in a healthcare setting) and she takes ALL the precautions. She has an opportunity to get the Pfizer vaccine. CDC and WHO say that pregnant women can get the vaccine, but that it is a personal choice based on risk/exposure to COVID. We know the risks of if she were to get COVID: More severe for pregnant women, and potential implications if close to delivery date. However, we also know that none of the COVID vaccines have data regarding impact of vaccines on still developing fetuses or the longer term implications on infants/toddlers. All that said, we do not have enough info that gives us some level of assurance about the safety of the vaccines on fetuses and their future cognitive/physical development after birth if exposed to the vaccine while in the womb… thoughts?

Answer: Thank you for sharing this background and complicated question. It really is problematic that pregnant and lactating women were precluded from joining the Pfizer and Moderna clinical trials; we’re operating with far from complete information. But we do know a few things that I’ll aim to synthesize herein to help you weigh the risks/benefits. For what it’s worth, I can also tell you that if it were me, I’d put increased weight on the risks we know rather than the theoretical risks; I’d take the vaccine.

In addition to what’s outlined below, this conversation that the Journal of the American Medical Association hosted on 2/8, is extremely informative, COVID Vaccination in Pregnant and Breastfeeding Individuals. And these recent articles from The New Yorker and National Geographic do a nice job synthesizing the issues too.

Risk of contracting COVID:

1. Risk of Infection?: We do not know whether pregnancy status is related to infection risk.
2. Risk of Severe Illness?: We do know that pregnancy status is associated with increased disease severity, with respiratory illness requiring hospitalization in 5% — 6% of pregnant women. Furthermore, CDC’s analysis of national surveillance data of ~400,000 women with symptomatic COVID-19 found that pregnant women were 3x more likely to be admitted to intensive care, 2.9x more likely to need mechanical ventilation, and 1.7x more likely to die as compared with non-pregnant women. We also know that COVID presents increased risk to the fetus.
3. Risk of Adverse Birth Outcomes?: There seems to be increased risk of pre-term birth among mothers who contract COVID. As synthesized in a recent article published in JAMA, “In studies of hospitalized pregnant women with COVID-19, which have included between 240 and 427 infected women, the risk for preterm delivery (both iatrogenic and spontaneous) has ranged from 10% to 25%, with rates as high as 60% among women with critical illness.” There may also be an increased risk of stillbirth, though the data are not conclusive on that point.
4. Risk of Vertical Transmission: Vertical transmission may occur and appears more likely among asymptomatic mothers, though vertical transmission is rare, especially as compared with other diseases.

Risk of vaccination:

1. Risk to Pregnancy?: There is no risk of acquiring the disease from the mRNA vaccine. Additionally, as Dr. Fauci stated earlier this month, “We had a lot of pregnant women vaccinated [over 10,000]. The FDA followed them and will continue to follow them.. Even though we don’t have good data on it, the data that we’re collecting on it so far has no red flags.” Other vaccines given to pregnant women, including influenza and pertussis, have proven safe and effective.
2. Risk to Fetus?: As the American College of Gynecology and Obstetrics (ACOG) synthesized, animal studies of the Pfizer and Moderna vaccines indicate there are “no direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition or post-natal development.” One potential risk of vaccination is the potential side effect of high fever. High fever in early pregnancy has been linked to neural tube defects among women who are not ingesting at least 400g of folic acid/day.
3. Risk to Infant/Child?: There is little in the way of plausible theoretical risks to the infant/child. The Academy of Breastfeeding Medicine recently issued a statement concerning vaccination and breastfeeding, stating “While there is little plausible risk for the child, there is a biologically plausible benefit. Antibodies and T-cells stimulated by the vaccine may passively transfer into milk.” The Academy further addressed mRNA lipid nanoparticles that encode the ribosome instructions, stating “ it is unlikely that the vaccine lipid would enter the bloodstream and reach breast tissue. If it does, it is even less likely that either the intact nanoparticle or mRNA transfer into milk. In the unlikely event that mRNA is present in milk, it would be expected to be digested by the child and would be unlikely to have any biological effects.” Turning to other vaccines, we have strong data indicating that influenza vaccination in pregnancy can reduce the risk of low birth weight by 15% and infant influenza illness by 30%. And pertussis vaccine during the 3rd trimester has been proven to reduce the risk of infant pertussis illness by 85% thanks to antibody transfer in utero.

Q&A for 2/9:

#Trends #KY #TN #TX #VA

Question: And how about trends for Kentucky, Tennessee, Texas, and Virginia?

Answer: As promised, here are trends for KY, TN, TX, and VA. These trends are similar to the trends we observed in yesterday’s data with cases and hospitalizations declining after their peaks in January. Daily deaths in each of these four states are the highest they’ve ever been, but appear to be plateauing; hopefully we’ll see a true decline in the coming days. In the last week alone, 3,631 individuals across KY, TN, TX, and VA died of COVID. When it comes to testing, daily tests have either stagnated even fallen, as is the case in Kentucky. Meanwhile, test positivity remains exceptionally high with the 7-day rolling average ranging from 11% in Tennessee to 20% in Kentucky. Again, testing is not keeping apace with community spread. Please remain vigilant — wear your mask, wash your hands, keep your distance and as much as possible, avoid the 3Cs: closed spaces, crowded places, and close-contact settings.

Figure 1. Kentucky

Figure 2. Tennessee

Figure 3. Texas

Figure 4. Virginia

Q&A for 2/8:

#Trends #DC #MD #NY #USA

Question: What are the latest trends in New York and DC?

Answer: Here are the latest trends for the USA, New York, DC, and Maryland. I made these charts with data from covidtracking.com. Tomorrow, I’ll share trends for other states readers frequently ask about — Kentucky, Tennessee, Texas, and Virginia. If there are other states you’d like to see, please let me know. And here are a few overarching take-aways from these four figures:

1. After months of growth, testing has stagnated (avg. 1.6 million tests/day over the last week).
2. Test positivity has fallen. Across the country, test positivity has averaged 7.2% over the last week. Generally, positivity rates over 5% indicate that testing is not keeping pace with community spread. In New York, DC, and Maryland, test positivity is once again beneath the 5% threshold.
3. Daily cases have fallen dramatically since their peak earlier in January. Over the last week, the US averaged 117,000 cases/day. Obviously, daily cases are still very high, but the downward trend across the country as well as in New York, DC, and Maryland is a promising development. (Note: the spread of the UK variant is concerning given its increased transmissibility, which could lead to another explosion in cases. Please remain vigilant!)
4. The number of patients currently hospitalized across the country and in these three geographies has also begun to fall. Yesterday, 81,439 patients were hospitalized across the country, down from a high in early January of 132,464 patients hospitalized.
5. Daily deaths have plateaued in the country and DC. Daily deaths have even begun to fall in Maryland and New York. Even so, during the last week nearly 22,000 Americans died from COVID.

Figure 1. USA

Figure 2. New York

Figure 3. DC

Figure 4. Maryland

Q&A for 2/7:

#Vaccination #Immunity #Transmission Risk

Question: At the point where the 3 of us (my husband, adult son and I) are declared immune, having had the vaccine and waited the recommended time after the 2nd one), will it be safe for us to be together without masks or socially distancing?

Answer: There’s a bit of nuance here related to safety for your own health and safety for the health of others. When it comes to your own health — and that of your husband and son — you can rejoice! However, when it comes to protecting the health of other non-vaccinated people, you must continue to be cautious and follow best public health practices, including masking and social distancing.

Your Own Health

Once you’ve waited several weeks after your second vaccine dose, your body should have built up strong immunity to protect you against becoming sick with COVID. We know this based on data from Pfizer and Moderna clinical trials. With this backdrop, your husband, son, and yourself can be together without masks or social distancing and free from worry that one of you will unwittingly make the other sick. Yay!

Other People’s Health

BUT, we still don’t know whether the Pfizer or Moderna vaccines protect against infection and transmission! This means that it’s possible that one or more of you could unwittingly become asymptomatically infected and spread the virus to others. If that spread reaches someone who has not yet been vaccinated, it could have dire consequences. This is why it is imperative that people who are vaccinated continue to be cautious and follow public health practices. As CDC states, “This includes wearing a mask, staying at least 6 feet away from others, avoiding crowds, washing hands often, following CDC travel guidance, following quarantine guidance after an exposure to someone with COVID-19, and following any applicable workplace or school guidance, including guidance related to personal protective equipment use or SARS-CoV-2 testing.” For more background on this issue, see our Q&A of 1/11.

Q&A for 2/6:

#Risk #Underlying conditions

Question: Are there any studies done on people who eat healthy, exercise, don’t smoke, rarely get sick, take the proper amount of vitamins/minerals and have no comorbidity and how this affects the person contracting Covid 19 or not?

Answer: As Dr. Fauci said in December, “There’s something very strange about a virus that in most people barely bothers them and in others it kills them. We still don’t understand why that’s the case right now.”

• We do know that disease severity increases with age, racial/ethnic minority status, and underlying conditions (see Q&A of 11/18). Global estimates indicate that case fatality rates are higher among men than women.
• Many researchers also hypothesize that genetics related to innate immune response and inflammatory response respectively play a role in susceptibility to infection and disease severity (see Q&A of 12/15). And a growing body of research shows that O blood type, especially O negative blood type, may be protective against COVID-19 infection and severity.
• There’s also accumulating evidence indicating that disease severity increases as a person’s exposure to the virus increases (see Q&A 10/25).
• Further, when it comes to susceptibility to infection, we have a mixture of infected host, environment, and the susceptible host factors that influence whether or not a person becomes infected (see Q&A of 11/16).

To summarize, we likely have a mixture of socio-demographic, genetic, and environmental factors influencing susceptibility and disease severity. There’s no special vitamin or exercise or food a person can take/do to protect against COVID — though it’s always good to maintain overall health! Instead, the best way to avoid infection is to wear your mask, wash your hands, keep your distance, avoid the 3Cs — closed spaces, crowded places, and close-contact settings, and get the vaccination when it’s your turn!

Q&A for 2/5:

#Vaccination #Fertility #Pregnancy

Question: My sister is trying to get pregnant. Should she get vaccinated when it’s her turn?

Answer: Yes! The American College of Obstetrics and Gynecology (ACOG) “recommends vaccination of individuals who are actively trying to become pregnant or are contemplating pregnancy… Additionally, it is not necessary to delay pregnancy after completing both doses of the COVID-19 vaccine.” This recommendation aligns with that of the American Academy of Reproductive Medicine, whose recommendations further specify that individuals undergoing fertility treatments should be encouraged to receive the COVID vaccine.

Q&A for 2/4:

#Vaccination #Mild Illness

Question: My friend was just diagnosed with shingles, and also just found out she can get a covid vaccine tomorrow. Her doctor, who diagnosed her mild case of shingles, told her not to get the shot. She has a daughter who has a double lung transplant and she really wants to get the inoculation to protect her daughter. Can you tell me if she should decline the shot? She doesn’t like or trust this new doctor. She wonders if she goes ahead and gets the shot, would that be worse than waiting to get the vaccine

Answer: As you know, I’m not a medical doctor. First things first, your friend should get a second opinion, ideally from a doctor she trusts. If the doctor is unsure, I recommend that they reach out to vaccine specialists associated with CDC’s Clinical Immunization Safety Assessment (CISA) Project. CISA is designed for US-based healthcare providers and health departments to receive consultation on questions that are (1) about an individual patient or vaccine safety issue and (2) not readily addressed by CDC or Advisory Committee on Immunization Practices (ACIP) guidelines. Her doctor can make the request by calling 800-CDC-INFO.

Broadly speaking, mild illness is not a contraindication for vaccination. Indeed, CDC’s clinical guidelines for mRNA vaccination against COVID list “moderate to severe acute illness” as a precaution to vaccination, however, “mild illness” is neither listed as a precaution nor a contraindication. (Table 1) ACIP’s General Best Practices for Immunization confirm that “the safety and efficacy of vaccinating persons who have mild illnesses have been documented.” Again, mild illness should not preclude a person from being vaccinated.

In the case of COVID, note this important exception: If you are mildly sick with COVID, have recently been exposed to COVID and are still in your quarantine window, or are asymptomatically infected and within the 10 day window since having tested positive you should wait to get vaccinated until you are recovered and/or out of quarantine/isolation so that you do not further spread the virus.

Table 1. Triage for individuals coming for vaccination (from CDC)

Q&A for 2/3:

#Vaccination #Ibuprofen

Question: I am scheduled to take my 2nd Moderna shot next Wed. Is it contraindicated to start taking ibuprofen 1-2 days in advance? I am concerned I may not feel well after.

Answer: As a reminder, I am not a medical doctor. Please consult your doctor. In the meantime, based on what I’ve read (synthesized below), you should *not* take any oral pain relievers (acetaminophen or ibuprofen) before vaccination. If pain occurs after vaccination, you should first check with your doctor; WHO’s guidelines indicate that you can take oral pain relievers during the days following vaccination.

1. WHO’s 2015 position paper, “Reducing pain at the time of vaccination”, states “Several of the interventions that were considered are not currently recommended due to lack of evidence of pain-mitigation effectiveness and/or the potential for altering vaccine effectiveness. These include… administration of oral analgesics (e.g. acetaminophen, ibuprofen) before or at the time of vaccination. If pain occurs later, during the days after vaccination, oral analgesics can then be given to mitigate pain and/ or fever linked to delayed reactogenicity.”
2. Clinical guidelines for vaccine-related pain management developed by an independent, cross-Canada multidisciplinary team state “We suggest against giving ibuprofen before vaccine injections.”
3. Recent studies related to vaccine effectiveness and acetaminophen/ibuprofen use in infants have found “Prophylactic use of antipyretic/analgesic drugs can reduce immune responses to some infant vaccines, warranting judicious use.”
4. CDC’s “What to Expect after Getting a COVID-19 Vaccine” recommends that “If you have pain or discomfort [after being vaccinated], talk to your doctor about taking an
   over-the-counter medicine, such as ibuprofen or acetaminophen.”
5. ABC News recently ran a story on this issue and consulted with leading infectious disease doctors who confirmed that you should not take pain relievers before getting vaccinated. “We do not recommend premedication with ibuprofen or Tylenol before COVID-19 vaccines due to the lack of data on how it impacts the vaccine-induced antibody responses,” said Dr. Simone Wildes, an infectious disease specialist at South Shore Medical Center and a member of Massachusetts’ COVID-19 Vaccine Advisory Group.

Q&A for 2/2:

#Communication #Disinformation

Question: A friend sent me this rant on COVID mRNA vaccines yesterday afternoon. This person is one of the people who think the vaccine will change your DNA. I wondered how you would respond to her. I’m just a bit speechless!

Answer: This is such a challenging issue that impacts all of us in this pandemic age of misinformation and social media amplification of anti-vaccination messages. I’m not sharing the conspiracy here because sadly, anytime you repeat anti-vaccination information, you risk inadvertently reinforcing the misinformation you’re trying to correct. I suppose that’s my first piece of advice. Don’t repeat the conspiracy. The next thing you need to consider is this:

Is it worth your time and effort to engage? If the person or group you are engaging with is a vocal vaccine denier, it’s probably not worth your time or effort to engage. They are unlikely to change their mind (Figure 1). That said, most people who express vaccine hesitancy are not in that denier category and you’re more likely to change their mind with ongoing dialogue. And this brings me to my next point…

We need to be proactively sharing pro-vaccination information and messages. The more readily available true information and personal stories are, the less likely a person is to get pulled into misinformation. We need to be sharing truthful vaccine messages and stories often, vocally, and in diverse communities (online and offline) in order to prevent misinformation from sticking. If we don’t, we risk the still small anti-vaccination movement overwhelming pro-vaccination voices online and beyond. (Reminder, Q&A of 12/5 describes how mRNA vaccines work.) Clearly with your friend, we’ve already missed the boat on proactively sharing pro-vaccine information. Now we come to the crux of your question:

How do we respond to vaccine misinformation? WHO offers an exceptionally easy-to-read and informative Best Practice Guidance to Respond to Vaccine Deniers in Public. If you’re on a public social media feed or the like, I think the advice works there too. Here’s the synthesis: 1. Remember the general public is your target audience, not the vocal vaccine denier; 2. Aim to correct the content AND unmask the techniques that the vocal vaccine denier is using; 3. Remember the goal is to make the public audience more resilient against anti-vaccine statements and stories; support the people expressing vaccine hesitancy in their vaccine acceptance decision. When it comes to responding, follow these key steps:

• Have three key messages ready. For example: You can help stop the pandemic by getting a COVID-19 vaccine. COVID-19 vaccines are safe and effective. These vaccines cannot give you any disease.
• Keep your three messages simple.
• Repeat your three messages as often as possible.
• Stick to the facts and do not repeat any anti-vaccination messages.
• Emphasize the positive (e.g. high safety and low risk).
• Use inclusive terms (e.g. as a member of the community; as a parent…).
• Do not question personal motivation.
• Tell the truth. If you don’t know, don’t pretend to know.
• Communicate what has been achieved/what is known and what is still to be achieved/still unknown.
• Avoid humor.
• Underline scientific consensus.
• Emphasize social benefits.

What about responding one-on-one? Here, you want to foster open dialogue. Ask open-ended questions. Be respectful. Do not question personal motivations. Share personal stories. Do not get into much of a facts-based argument. This article published in The Atlantic back in October offers more details on these suggestions plus a few more. And this handbook, The Debunking Handbook, also includes a wealth of research, tools, and processes.

Figure 1. Probability to change mind to vaccine acceptance (from WHO)

Q&A for 2/1:

#Masks #Filters

Question: Is inserting a PM2.5 filter into a cotton or silk mask’s filter pocket as protective as double masking?

Answer: Yes, based on what we currently know, adding PM2.5 filters is as protective as double masking. Returning to the Q&A of 1/26 on double masking, wearing a three-layer mask that has “outer layers consisting of a flexible, tightly woven fabric that can conform well to the face and a middle layer consisting of a non-woven high-efficiency filter material (e.g., vacuum bag material)” is highly effective. Put in more straightforward terms — wearing a tightly woven mask that has 3 layers, including a filter in the middle, is highly effective. And since you mentioned silk, I thought I’d add one interesting finding CDC reported, which is that silk may help repel moisture droplets, thereby reducing fabric wetting and increasing comfort. And as a reminder, Figure 1 shows CDC’s Do’s and Don’ts for masks.

Figure 1. CDC Mask Recommendations (from CDC)

Q&A for 1/31:

#Schools #Transmission

Question: Can the risk of COVID be mitigated for teachers? More broadly, should DC be reopening schools when the pandemic is at an all-time high rate of infection?

Answer: The risk of COVID can be mitigated (but not erased) by implementing a number of protective measures, including masking, podding, social distancing, hand washing, cleaning, screening, and proper ventilation (see Q&A of 9/30). Of course, vaccination will also be extremely important and our teachers need to be provided vaccinations as soon as possible! When it comes to whether or not DC should be reopening schools at this stage of the pandemic, clearly there are strong opinions on both sides (reopen or stay virtual), with each side having valid arguments supporting those opinions. I found this recent article from CDC researchers that JAMA published a few days ago helpful for parsing through what needs to be done, “Data and Policy to Guide Opening Schools Safely to Limit the Spread of SARS-CoV-2 Infection.” I attempted to synthesize the article’s main points and then add my own sub-bullet on areas where DC seems to be succeeding (green flag), those where the city is questionably succeeding (yellow flag), and those where the city seems to be challenged (red flag):

1. Addressing and reducing community spread “through policies to interrupt transmission (eg, restrictions on indoor dining at restaurants).”

• Red flag: DC’s community transmission rates are still high with 3,125 cases in the last 14 days, equating to 444 cases per 100,000 people over the last 2 weeks. Per CDC’s school reopening benchmarks, this puts DC in the highest transmission risk category (>200 cases/100,000). Additionally, DC has recently eased restrictions on indoor dining, allowing for 25% capacity indoors.

2. Making school spaces as COVID safe as possible, “requiring universal face mask use, increasing physical distance by dedensifying classrooms and common areas, using hybrid attendance models when needed to limit the total number of contacts and prevent crowding, increasing room air ventilation, and expanding screening testing to rapidly identify and isolate asymptomatic infected individuals.”

• Yellow flag: It appears that DC is working hard to implement these measures, per its risk mitigation commitments are here (Figure 1). DC also aims to start vaccinating its public school workforce this month. However, the teacher’s union is meeting an arbiter to determine if their agreement with the school board was breached as related to safety promises made/delivered.

3. Providing the option of remote school, “Staff and students should continue to have options for online education, particularly those at increased risk of severe illness or death if infected with SARS-CoV-2.”

• Yellow flag: Families have the choice whether to send their child to in-person learning. Per DC’s School Chancellor, “Families will always have a choice to have their student remain learning at home, and there is no requirement to accept an in-person learning seat.” However, as well described in this recent Washington Post article, the current reopening plans are spotlighting inequities. “Twice as many families rejected an offer to return to an elementary school in the poorest ward than in the wealthiest one.” Furthermore, as the article reports, the number of teachers returning to in-person teaching is much higher proportionally than those teaching students learning remotely. If resources are diverted to better support in-person learning, we’ll have separate and unequal schooling largely divided along racial and economic lines.

4. Limiting school-related activities “such as indoor sports practice or competition that could increase transmission risk.”

• Green flag: DC public schools have suspended all high school sports and extracurricular activities through March 17th (the current duration of the public health emergency).

Figure 1. DC Public Schools Health and Safety Commitments (from DC Reopen Strong)

Q&A for 1/30:

#Schools #Transmission

Question: The DC public schools are supposed to be reopening on Monday. Teachers have objected saying it still isn’t safe and some critics have responded that child to adult (particularly elementary school age kids) transmission of COVID is rare. Is it true that child to adult transmission is rare?

Answer: While I would not say that child to adult transmission is rare (it does happen), I would say that accumulating evidence indicates younger children are less likely to transmit the virus as compared with adolescents and adults. We do not yet know whether new variants impact this dynamic. Read on for more details.

The European CDC updated its technical report on children and the role of school settings on 23 December. It incorporates findings from several analyses, including a literature review of available scientific research from around the world published as of 18 November. It’s a really informative read. With regard to this question, the European CDC’s key messages are:

• “Younger children (preschool and primary school aged) appear to transmit SARS-CoV-2 less often than adolescents and adults (low confidence), but younger children may also have been tested for SARS-CoV-2 less frequently than other age groups, while also having fewer opportunities for social mixing during periods of school closures than adolescents.
• “Onward transmission by adolescents may occur as often as by adults in household and community settings, given social mixing patterns (moderate confidence).”
• Note: “low confidence” means that the research “provides some indication of the likely effect” whereas “moderate confidence” means that the research “provides a good indication of the likely effect.” Ideally we’d like evidence to accumulate to the degree that we have “high confidence.”

Since the literature review concluded, a few more studies on this topic have been published. These studies further confirm that younger kids are less likely to transmit the virus. For example:

• In early December, Clinical Infectious Diseases published “A meta-analysis on the role of children in SARS-CoV-2 in household transmission clusters,” which found that children are infrequently identified as the index case of household clusters (e.g. they are not often the person who likely brought infection into the household).
• In mid-December, National Geographic published a report on a not-yet-peer-reviewed study out of Iceland led by the deCode Genetics research company. As NatGeo reports, this 40,000-person study found that children under 15 were about half as likely as adults to be infected, and only half as likely as adults to transmit the virus to others. Almost all the coronavirus transmissions to children came from adults.”
• Earlier this month, Pediatrics published “COVID-19 Transmission in US Child Care Programs,” which found that “exposure to child care during the early months of the US pandemic was not associated with an elevated risk for COVID-19 transmission to providers.” [note: these data were drawn in the context of the first 3 months of the pandemic with strict public health measures being practiced in child care programs, and the data are drawn primarily from settings with children <6 years of age]

Q&A for 1/29:

#Masks #Travel

Question: I saw that Lufthansa now has a requirement of only certain types of face masks on their flights, including no cloth masks. Is this to address concerns that you’ve highlighted in 1/26 Q&A? I couldn’t find a good explanation on their website.

Answer: Yes! Masks are some of the best tools we have to prevent viral spread. With new, more contagious variants circulating, we want the masks people wear to be highly effective, which means double masking (as discussed the other day) OR wearing medical grade, higher filtration masks like KN95s (see Q&A of 11/20). When it comes to the Lufthansa question — Lufthansa is a German airline and it appears that they are following the new German regulations. As NPR reported earlier this week,

“In Germany, the federal and state governments introduced measures last week making medical masks — identified as surgical masks or KN95 or FFP2 masks — mandatory in stores and on public transit. It also issued a recommendation that medical masks be worn whenever there is close or prolonged contact with other people, particularly in enclosed spaces…. The government said that in light of the new coronavirus variants, medical masks “offer greater protection than normal cloth masks, which are not subject to any standards with regard to their effectiveness.”… “We must take the danger posed by this variant very, very seriously, and we must slow the spread of this variant as far as possible,” said Chancellor Angela Merkel.”

Austria and France have similar measures as further described in the NPR article. Note: The U.S. CDC continues to recommend that the general public avoid using surgical masks or N95 masks since “surgical masks and respirators are critical supplies that should be reserved for healthcare workers and other medical first responders to prevent supply shortages.” This guidance does not apply to KN95 masks or non-medical disposable masks.

Q&A for 1/28:

#Variants #Transmission

Question: How much of the current spike in infections do we think is related to holiday visits and how much to more contagious strains?

Answer: To my knowledge, most epidemiologists believe that the recent surge in infections in the US was the result of human behavior rather than a more contagious variant. The fact that cases and hospitalizations have been falling in the last couple of weeks lends credence to this hypothesis. However, most public health professionals (including me) are very concerned about the potential for cases, hospitalizations, and deaths to begin rising again because of the new, more contagious variants. This possibility is all the more fraught because the US’s genomic sequencing (e.g. surveillance for variants) has been paltry. We have been nearly blind to new variant development and spread in the country.

We likely have much more of the UK variant and other variants circulating than we currently know. As of 27 January, CDC has found a total of 315 cases caused by the UK variant (B.1.1.7) in 28 states across the US. This total represents *only* those cases identified through a sampling of SARS-CoV-2 positive specimens; it does not represent the true total. The US has been behind in genomic sequencing efforts, ranking 43rd in the world. As Nature reported earlier this month, “The number of SARS-CoV-2 genomes that the United States has shared on GISAID [global virome sequencing database] is less than 0.3% of its total number of COVID-19 infections. That compares with nearly 5% for the United Kingdom, 12% for Denmark, and almost 60% for Australia (see ‘Global surveillance’).” The lack of a national system means that individual academic laboratories do most sequencing rather than the country’s large genomic centres; states with many active sequencing labs are likely to discover more circulating variants and states with fewer sequencing labs may be totally blind.

It’s imperative that we double down on public health measures — social distancing, mask wearing, hand washing, avoiding crowded places, closed spaces, and close-contact settings — while increasing vaccinations and expanding our genomic sequencing efforts to keep the new variants from ripping through our weakened country. In that vein, the Biden administration has committed to expanding genomic surveillance with CDC currently working to double sequencing efforts.

Q&A for 1/27:

#Vaccine Distribution

Question: Why has vaccine distribution been so challenging?

Answer: To summarize, I would say that the problems are these:

• We don’t yet have enough vaccines to go around.
• Vaccine administration has been overly decentralized with each locality, sometimes each provider, left to create their own vaccine implementation system.
• In the context of limited supply and decentralization, localities are straining to plan and implement their vaccination campaigns — especially in light of limited funding, limited human resources, and health care and public health systems already overstretched responding to COVID patients and community spread.
• This strain is compounded by lack of timely data from the federal government to states and from states to localities on how many doses to expect and when to expect them.
• The lack of timely data seems to be a product of an overly complex vaccine information system in which different government entities “own” different components:
• HHS/BARDA maintains the manufacturing/production information system (e.g. how many doses to expect from vaccine production);
• The Operation formally known as Warp Speed maintains the transit logistics data system and state allocations planning tool (Tiberius);
• The CDC maintains the vaccination administration data system (VTrckS) and provides technical assistance to states to help plan allocation needs; and
• Commercial partners (like CVS), States and Territories, and Federal partners each feed information (e.g. vaccines administered and doses on hand) into various data streams, making the reporting cumbersome, complex, and lagged generally 3+ days.

The new Administration is working to resolve these problems. For example, yesterday, President Biden announced that the number of doses going to states would increase to 10 million/week for the next 3 weeks, up from 8.6 million/week currently. He also announced the plan to purchase 200 million more doses of vaccine with the aim of having enough doses for all adults to be vaccinated by this summer. The Administration’s $1.9 trillion American Rescue Plan includes a good deal of funding to states and localities to fill gaps in COVID response, including vaccine implementation with a promise to hire 100,000 Americans to support the public health response effort (hello, Health Force!). And his National Strategy for the COVID-19 Response promises to “improve the allocation process by providing states and their localities with clear, consistent projections to inform their planning.” The Strategy also promises that the Administration will “fully leverage the Defense Production Act to fill any distribution gaps” and commits the Department of Health and Human Services to “release guidelines for redistribution within states as needed and where appropriate.”

If you’d like to read more, this article published last week in Time, The U.S. Fumbled Its Early Vaccine Rollout. Will the Biden Administration Put America Back on Track?, provides more detail.

Q&A for 1/26:

#Double Masking

Question: One question I had regarding this new variant, some parents have said that they are double-masking now. Is this any more protective than standard measures? I know there is probably a lot of uncertainty in this question, but does double masking provide much more of a benefit for regular interactions, like grocery store, etc.?

Answer: Yes, evidence indicates that double masking is more protective than single masking. Even Dr. Fauci told NBC yesterday that double masking “likely does” help protect against the mutant strains, “It just makes common sense that it would be more effective.” This new(ish) practice began to gain steam after a December commentary published in Cell picked up a lot of traction, Uniting Infectious Disease and Physical Science Principles on the Importance of Face Masks for COVID-19. The commentary summarizes the evidence on face masks for preventing COVID-19 and concludes with the following set of recommendations for the general public, including the recommendation for wearing a cloth mask tightly on top of a surgical mask for maximal protection (Figure 1):

Based on our and others’ results, we recommend a high-quality surgical mask or a fabric mask of at least two layers with high thread count for basic protection (Figure 1, top panel) for the public. For maximal protection (Figure 1, bottom panel), members of the public can either (1) wear a cloth mask tightly on top of a surgical mask where the surgical mask acts as a filter and the cloth mask provides an additional layer of filtration while improving the fit; or (2) wear a three-layer mask with outer layers consisting of a flexible, tightly woven fabric that can conform well to the face and a middle layer consisting of a non-woven high-efficiency filter material (e.g., vacuum bag material). If the masks fit well, these combinations should produce an overall efficiency of >90% for particles 1 μm and larger, which corresponds to the size of respiratory aerosols that we think are most important in mediating transmission of COVID-19.

If you’d like to read more, this article published in The Cut yesterday is helpful, Time to Start Double-Masking, as is this one published a couple of weeks ago in the NY Times, One Mask Is Good. Would Two Be Better?

Figure 1. Recommended masks for public (from Cell)

Q&A for 1/25:

#Vaccination #Prioritization #General Population

Question: As companies strain to produce sufficient vaccine quantities to meet overwhelming demand, when can we expect that there will be sufficient vaccines to cover healthy adults 30–40 working from home (a non-prioritized group)? Or is vaccination not as important in this age group since the majority of the adult population would have been vaccinated by the time we reach this group?

Answer: Healthy adults <65 years of age who are not essential workers will be vaccinated in general population vaccination campaigns (Phase 2, Table 1). When it comes to timing of the general population vaccination campaigns, I’m going to turn to some simple math and make some simple assumptions, which I’ve described below. If the assumptions hold, I think we could expect the general population vaccination campaign to kick into gear in the summer and reach 80% coverage by end-September. And given how quickly we moved between earlier phases, I suspect that we’ll start the general population vaccination campaigns as early as May/June. Of course, this estimate is super back-of-the-envelope and overly simplistic, but it’s at least a starting point to set some expectations. Finally, vaccination is important for all age groups, even non-prioritized ones!

1. The US has a population of ~332 million, of whom ~66 million are ages 0–15. (US Census Bureau). Since we do not yet have vaccine safety/efficacy information for the youngest members of our population (those ages 0–15), we can expect they will be among the last to get vaccinated. Note: clinical trials are underway to assess vaccine safety/efficacy among children.
2. This means that ~266 million individuals are in the line ahead of children.
3. Of those ~266 million, ~202 million are in prioritized groups 1a-1c (see Table 1).
4. This means that ~202 million individuals are in line to receive the vaccine before we get to the remaining ~64 million healthy, non-essential workers ages 16–64.
5. President Biden has a goal of 100 million vaccines within the first 100 days of his administration. Note: this is 100 million doses, not full vaccinations. According to Bloomberg Vaccine Tracker, the US has already administered 22.4 million shots, of which 17.1 million were administered before President Biden took office. If President Biden’s goal is achieved, we can expect to have administered 117 million doses by April 30th.
6. This is the equivalent of 58.5 million individuals fully vaccinated by April 30th. (note: many experts think we can achieve higher rates of vaccination as systems improve and production ramps up)
7. If the pace continued at 1 million doses/day, we would expect to have:

• 108.5 million individuals fully vaccinated by August 8 (1/3 of our whole population). (200 days)
• 158.5 million individuals fully vaccinated by November 16. (300 days)
• 208.5 million individuals fully vaccinated by February 24, 2022 (78% of our adult population). (400 days)

8. But that goal is too limited since distribution challenges are being addressed, production is ramping up, and additional vaccines are in the pipeline for FDA review/authorization. So let’s say that we double the pace after the first 100 days (2 million doses/day):

• 158.5 million individuals fully vaccinated by August 8 (nearly 1/2 of our whole population; 60% of our entire adult population).
• 212.8 million by October 1, 2021 (80% of all adults would be fully vaccinated, which is perhaps close to the upper limit of adult vaccinations given issues of acceptance and conditions precluding vaccination like a history of severe allergic reaction)
• 258.5 million individuals fully vaccinated by November 16.

Table 1. Prioritized Vaccine Group Population Size (millions) (from CDC)

Q&A for 1/24:

#Vaccination #Asymptomatic Infection

Question: Once you are vaccinated, can you still get infected with the SARS-CoV-2 virus? My understanding from watching the FDA proceedings on Moderna and Pfizer vaccines is that vaccinated individuals are protected from severe consequences (illnesses and sickness) resulting from SARS-CoV2, but they can still get the virus (and transmit to others) once they are immune. So while a vaccinated person is largely protected from getting sick, they can still be infected with the virus after being vaccinated. My mother, who is a critical care pulmonologist, said her understanding was that a vaccinated person would no longer acquire SARS-CoV2. It’s a nuance that’s come up quite a bit in my conversations with family over the past week, and I’ve found little data on this particular issue.

Answer: The short answer is that we just don’t know yet. The Pfizer and Moderna clinical trials had primary endpoints of symptomatic infection (e.g. sickness), but the data have been insufficient to assess asymptomatic infection. Basically, a vaccinated person has a good deal of protection from becoming sick with COVID, but we don’t know whether they have protection from becoming infected and contagious. This is why it’s so important that vaccinated individuals continue to follow public health protocols, including mask wearing and social distancing. Our Q&A of 1/11 discusses this issue in more detail.

Since then, a bit more potentially good news has surfaced. Israel’s Clalit Institute released its preliminary (not yet peer reviewed) analysis of infections following vaccination. Researchers compared the rate of laboratory confirmed test positives between individuals ages 60+ who received the first Pfizer dose and those who were unvaccinated. Researchers found that “14 days after the injection of the first vaccine, there is a real decrease in the rate of infection.” If these study findings hold, it could mean that vaccination provides some protection against asymptomatic infection too. More research is underway to answer this important question!

Q&A for 1/23:

#Vaccination #1 dose #Efficacy

Question: What, if anything, is known about vaccine efficacy for either vaccine if someone only gets 1 shot?

Answer: We talked about this issue in our Q&A of 1/6. Since then (on 1/21), CDC updated its clinical guidance, stating [bold font is mine]:

“The second dose should be administered as close to the recommended interval as possible [21 days after first dose for Pfizer / 28 days for Moderna]. However, if it is not feasible to adhere to the recommended interval, the second dose of Pfizer-BioNTech and Moderna COVID-19 vaccines may be scheduled for administration up to 6 weeks (42 days) after the first dose. There are currently limited data on efficacy of mRNA COVID-19 vaccines administered beyond this window. If the second dose is administered beyond these intervals, there is no need to restart the series.”

Based on currently available analyses of the Pfizer clinical trial data published last month in the New England Journal of Medicine (NEJM), we know that the Pfizer vaccine efficacy in the interval between first and second dose is 52% (range: 30% to 68%) (Figure 1). As authors state, this finding indicates “early protection by the vaccine, starting as soon as 12 days after the first dose.” For Moderna, researchers report in their analysis of clinical trial data published last month in NEJM, “results from a preliminary exploratory analysis suggest that some degree of prevention may be afforded after the first dose.” The small number of infections + short follow-up time + non-random sample was too limited to draw firm conclusions about the degree of protection afforded by just 1 dose. That said, in the document Moderna submitted to the FDA, they also include efficacy data on those who had only received one dose at the time of interim analysis, showing an efficacy rate of 80% (range: 55% to 92%) with the caveat that the “small, non-random sample and short median follow-up time limits the interpretation of these results.” Both Pfizer and Moderna caution that the duration of protection afforded after just one shot is also unknown beyond the 21 day / 28 day interval. Studies designed to answer this question are ongoing.

If you’d like to read more, this article from The BMJ, Covid-19 vaccination: What’s the evidence for extending the dosing interval?, and this one from the BBC, How effective is a single vaccine dose against Covid-19? are both worth your time!

Figure 1. Efficacy of Pfizer-BioNTech Vaccine Over Time (upper box inset= after 1st dose, before 2nd dose) (from NEJM)

Q&A for 1/22:

#Vaccination #Infection

Reminder: Daily posts are online here: https://covidqanda.org. If you have a question, please ask!

Question: Could you tell me how long after a positive Covid test should a person wait to get the vaccine? A physician in my town stated that the CDC recommends waiting 90 days to maximize the effectiveness of the vaccine.

Answer: CDC’s clinical considerations for use of authorized vaccines, Pfizer and Moderna, are online here. Based on my read, your town’s physician is only partially correct. Here’s my synthesis:

• Even if you’ve had COVID, you should still be offered the vaccine.
• If you are sick with COVID (symptomatic), you should wait to receive the vaccine until you have recovered.
• If you are in self-quarantine due to COVID exposure, you should wait to seek vaccination until your quarantine period has ended. [note: this guidance does not apply if you are living in long-term care facility or other congregant setting]
• There is no recommended minimum interval between infection and vaccination… with one caveat.
• Caveat: If you received monoclonal antibodies or convalescent plasma as part of your COVID treatment, “vaccination should be deferred for at least 90 days, as a precautionary measure until additional information becomes available, to avoid potential interference of the antibody therapy with vaccine-induced immune responses.”

Q&A for 1/21:

#Vaccine Types

Question: Will you explain the different types of shots? I know Pfizer and Moderna are based on mRNA, but I also read that the Johnson and Johnson shot is based on an older technology. Can you explain the different technologies of the different shots that are coming?

Answer: Gavi, the vaccine alliance offers a really informative overview of the four kinds of vaccines in the world: whole virus, protein subunit, nucleic acid, and viral vector. As of 15 January, there are 64 vaccines against COVID in clinical trials. WHO offers a brief summary of each vaccine here, and I’ve provided Gavi’s definition of each vaccine type plus two examples of each type in the chart below (Chart 1). For the sake of time, I will focus on how viral vector vaccines work, since both the Johnson & Johnson and Astra-Zeneca vaccines are of the viral vector type. Basically, for both J&J and Astra-Zeneca vaccines, scientists take a little piece of genetic material from the SARS-CoV-2 spike protein and add it to a harmless adenovirus that has the ability to enter the cell, but does not have the ability to reproduce (meaning it can’t make you sick). Your body reacts to the perceived threat by making antibodies to that spike protein. Ultimately, if/when your body encounters the real SARS-CoV-2 threat, your immune system is prepared to respond. If you’d like more detail, this article from Prevention magazine is an informative, easy read. Meanwhile, this article from the New England Journal of Medicine, Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine may also be of interest, though it is a less easy read.

Finally, one exciting element of the Johnson & Johnson vaccine is that they are exploring the effects of both 1-dose and 2-dose regimens in clinical trials. Unlike the Pfizer and Moderna vaccines, it’s *possible* (not assured) that the J&J vaccine would only require one dose. That, coupled with less onerous cold storage requirements, means that if/when the J&J vaccine receives FDA and/or WHO authorization, distribution challenges would be greatly minimized.

*As a reminder, you can read more about how mRNA vaccines work in our Q&A of 12/5.

Chart 1. Vaccines Types (definitions from Gavi)

Q&A for 1/20:

#Vaccine Side Effects

Happy Inauguration Day!

Question: My coworkers were telling me that the 2nd shot is more likely than the 1st shot to cause side effects (like fever, muscle soreness). Is that a rumor or is it true?

Answer: It’s not a rumor; it’s true! Data from Pfizer and Moderna clinical trials show that side effects are more common after the 2nd dose. Still, more common side effects — like headache, fever, chills, tiredness, pain at injection site, muscle pain, and joint pain — should last no more than several days (usually 24–48 hours). For more on common side effects, see Q&A of 12/16.

Q&A for 1/19:

#Case Fatality Rates

Question: In almost every one of the charts you shared in the Q&A of 1/13 (except TN), every indicator is increasing but one — the rate of death. Why is the rate of death going down in each chart while everything else is going up?

Answer: The case fatality rate (CFR) that I present in the trend charts is a very simple indicator — the ratio of confirmed deaths to confirmed cases (deaths/cases). It is impacted by factors that influence the denominator (cases) and numerator (deaths), including:

• Number of cases captured: As testing becomes more widespread, we expect more asymptomatic and mild cases to be captured through testing, which will lower the CFR.
• Type of person infected: Case fatality varies dramatically by age and race (see Q&A of 11/18). As more young, otherwise healthy people become infected, the overall CFR will be weighted more heavily by youth and CFR will decline. The same can be said of race. Indigenous and Black Americans are more likely to die of COVID than White Americans This is a product of racism (see Q&A of 6/7). As the demographics shift and more White Americans become infected, CFR will decline.
• Geography of cases: CFR is impacted by the strength of a locality’s health system. Places with stronger health systems could see lower CFRs. If more cases are occurring in places with stronger health systems or if health systems overall have improved over time, we’d expect to see lower CFR.
• Treatment: As health care providers learn more about how to treat patients suffering from COVID-19, their treatments improve, causing health outcomes to improve, leading to fewer deaths and a decline in CFR.
• Partial immunity: This could be more important over the coming months, but is still hypothetical. As more people become vaccinated with the first dose, we can expect an increase in partial immunity, which could reduce the severity of disease. If vaccination doesn’t impact infection, but does impact disease progression, we would expect to see a decline in case fatality.

Case fatality rate will also depend on how you decide to measure it. Age-adjustment is important (see Q&A of 11/24). So is the recognition that deaths generally lag cases by 2+ weeks (see Q&A of 7/12 and Q&A of 11/22). Without lag, as of 1/18/21, the crude CFR for the US is 1.6%. Lagged by 2-weeks, it’s 1.9%. Lagged by 3-weeks, it’s 2.0% (Figure 1). Even with the lag, case fatality trends are declining over time in the US (see below) and this trend is also revealed in age-adjusted CFR (see Q&A of 11/24).

As I hope you can see from this overview, CFR is not a constant. Just as it has decreased, it’s also possible that it will increase. That said, if we can keep the most vulnerable among us from getting infected, if we can keep our health systems buoyed, if we can continue to improve our treatments, and if we continue to expand vaccination, we should expect case fatality rates to continue this downward trend. Finally, even low case fatality rates result in huge numbers of deaths if many of us are infected. And that’s what we’re tragically confronting with the US having experienced 399,015 deaths as of this morning.

Figure 1. Trends in CFR in the USA

Q&A for 1/17:

#Dosing Schedule #Vaccines

Note: There will be no Q&A tomorrow. Happy Dr. Martin Luther King Jr. Day!

Question: Well, it appears that we are going to run out of vaccines for a time and that means some folks will be left with more time between their first and second doses than recommended. So I guess my question is, what do we know from other vaccines about larger than recommended spacing between the first and second dose?

Answer: I’m not sure that we’ll “run out” of vaccines since production is supposed to be ramping up, but it’s a real possibility. Unfortunately, it is extremely challenging to know what’s going on with the US vaccine stockpile. We had understood that the USG held back distributing half of all vaccines in the stockpile for 2nd doses. In fact, just earlier this week HHS Sec. Azar stated that the administration would be “releasing the entire supply for order by states, rather than holding second doses in reserve.” As a result, states ramped up distribution capacity and invited a wider range of priority populations to make appointments for vaccination. By Friday, it became clear that all doses had already been distributed. Sec. Azar stated, “No. There’s not a reserve stockpile.” What a mess.

As to your question, we talked about changes to vaccine schedule in our Q&A of 1/6, but did not examine evidence from other vaccines. WHO offers this helpful set of recommendations for interrupted or delayed routine immunization (Table 1). As far as I understand it, the main issues are these five, for which I’ve provided a few examples (non-exhaustive!) as related to other vaccines:

1. Partial vaccination likely offers only partial immunity (i.e. people are still at some risk of disease after 1 shot)

• For example, the measles vaccine requires 2 shots. The first shot offers a great deal of protection (93% effective at preventing measles) but the second shot boosts the protection to 97%. For polio, the difference is greater with one dose having the protective efficacy of about 50% but two doses being about 80%-90% and 3 doses being 99%-100% effective.

2. Delaying/confusing the timing of 2nd dose could mean much greater loss to follow-up (i.e. many people only get 1 shot and remain at risk of infection/disease);

• In a study of vaccine delay among children, researchers found “Children whose parents intentionally delayed were significantly less likely to receive all vaccines by 19 months of age than children whose parents did not delay (35.4% vs. 60.1%, p<0.05).”

3. A partial immune response could push the virus to mutate faster;

• As described in this 2012 paper, “Partially effective immune response enough to exert selective pressure, but not effective enough to suppress escape viral mutants is the most effective driving force of antigenic variation.”

4. Changing the dosing schedule without adequate evidence could increase vaccine hesitancy (i.e. by confirming fears about the scientific rigor of the vaccine efforts);

• Among parents who express vaccine hesitancy about childhood vaccination schedules, perceptions of safety are a big driver of concerns. With regard to COVID, efforts to push vaccines out more quickly by changing the dosing schedule could reduce public trust.

5. Some interrupted vaccines require repeat of the 1st dose, though unlikely with the COVID vaccines, if it were the case, it would add more stress to vaccine production/distribution/administration.

• As shown in Table 1, most interrupted vaccines resume without repeating the first dose.

Table 1. WHO Recommendations for Interrupted or Delayed Routine Immunization (Sept. 2020)

Q&A for 1/16:

#Deaths #Norway #Nursing Homes

Question: I just read that Norway is investigating 23 deaths in frail and elderly patients after vaccination. I’m an older person with underlying conditions. Should I be concerned?

Answer: Short answer: Please talk with your doctor, and please know that there’s not yet any reason to be concerned. While the Pfizer trial did not include long-term care residents, it did include many older people with underlying conditions and no serious safety concerns were observed (see Q&A of 12/10). Read on for more details.

Norway Experience

The BMJ published a news report on this issue yesterday, which is a helpful synthesis that also provides an answer to your question. In response to 23 frail, elderly nursing home residents in Norway having died shortly after receiving the Pfizer vaccine, Steinar Madsen, medical director of the Norwegian Medicines Agency (NOMA), told The BMJ, “It may be a coincidence, but we aren’t sure… There is no certain connection between these deaths and the vaccine.” He further stated, “We are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease… We are now asking for doctors to continue with the vaccination, but to carry out extra evaluation of very sick people whose underlying condition might be aggravated by it.” The BMJ reports, “This evaluation includes discussing the risks and benefits of vaccination with the patient and their families to decide whether or not vaccination is the best course.”

Coincidence vs. Causation

Deaths in nursing homes are common. As discussed in our Q&A of 5/27, during non-COVID times about 21% of all deaths in the USA occur in nursing homes (534,714 deaths in nursing homes in 2017). Given this reality, it’s very difficult to untangle whether the nursing home deaths that occur soon after vaccination are coincidence or actually related to the vaccination. Indeed, this was one of the main reasons the CDC vaccination advisory panel’s lone dissenter voted against prioritizing residents in long-term care facilities. As STATNews reported last month, Advisory Committee on Immunization Practices (ACIP) member Helen Keipp Talbot “warned that vaccinating this population at the start of the vaccine rollout is risky, because long-term care residents have a high rate of medical events that could be confused as side effects of vaccination and undermine confidence in the vaccines. “And I think you’re going to have a very striking backlash of, ‘My grandmother got the vaccine and she passed away,’” she said at the time.” In an interview with STATNews she elaborated, “I fear a loss of confidence in the vaccine. That the vaccine will actually truly be safe, but there will be temporally associated events and people will be scared to use the vaccine. And we won’t be able to get our kids back in school and people back at work — the things that are important.”

Q&A for 1/15:

#Vaccines #Escape #Mutations

Question: What is immune escape?

Answer: Immune escape (aka viral escape and antigen escape) is the ability of a virus to elude an individual’s immune response. In the context of new SARS-CoV-2 strains, the term has come to prominence as scientists examine whether the new strains exhibit immune escape in terms of vaccine resistance. In good news, initial data show that “existing vaccines should work against new coronavirus variants — for now.”

Unlike drug resistance, which is common, vaccine resistance is rare (Figure 1). This paper published in 2017, Why does drug resistance readily evolve but vaccine resistance does not?, offers a useful hypothesis to explain this dichotomy: 1) Vaccines tend to work to prevent disease whereas drugs tend to work to treat disease (i.e. vaccines generally give fewer opportunities for viral replication and spread to others); 2) Vaccines tend to induce immune responses against multiple targets on the virus whereas drugs tend to target very few (i.e. unlike drugs, vaccines generally require immune escape from multiple targets). A more recent paper from these same authors published in November in PLoS Biology describes one more feature of a vaccine that limits resistance: generally, the immune response elicited by the vaccine protects against all circulating types of the virus. What we know of the vaccines we currently have against COVID is that they do meet all three criteria — 1) they prevent disease (though we still don’t know whether they prevent infection); they induce a complex immune response; and 3) they work against all currently circulating variants.

If you’d like to read more, this Nature article published last week is an informative read as is this National Geographic article published earlier today.

Figure 1. Time to first detection of human pathogens resistant to vaccines and antimicrobial drugs (from Kennedy DA, Read AF. Why does drug resistance readily evolve but vaccine resistance does not?. Proc Biol Sci. 2017;284(1851):20162562)

Q&A for 1/14:

#Vaccines

Question: Will you take the vaccine when it’s your turn?

Answer: Absolutely! I want to protect myself and help stop the pandemic. Evidence from robust clinical trials shows that the two vaccine authorized — Pfizer and Moderna — are safe and more than 90% effective at preventing disease.

I recognize that many of us are hesitant about taking the vaccine and have important concerns that we can and should be addressing. I also recognize that concerns vary from person to person. If you’re someone who is hesitant, I invite you to share your concerns with me. I’d welcome the opportunity to talk them through. In the meantime, for more information on vaccine safety and efficacy, see Q&A of 12/16, Q&A of 12/17, and other #vaccine posts.

Q&A for 1/13:

#Trends

Question: I read today that the US surpassed 4,000 daily deaths yesterday. Would you please share updated trends for the USA, New York, and other states you usually show?

Answer: Yesterday’s death count represents yet another grim milestone (a sad phrase surprisingly missing from the 2021 banished words list). Here are charts for the USA, New York, DC, and states folks have asked about in the past — Maryland, Virginia, Kentucky, Tennessee, and Texas. If you want to see charts for another state, let me know. I made these figures using data from The COVID Tracking Project. A few highlights:

1. Across the country, we experienced 23,119 deaths in the last week alone. That’s more deaths in one week due to COVID than the entire number of deaths from the 2019–2020 flu season (22,000 influenza deaths; range: 18,000–29,000, CDC preliminary estimates).
2. No state has been spared. As you’ll see in these charts, cases, hospitalizations, deaths, and test positivity are high and increasing.
3. Testing seems to have stagnated over the last month across the country.
4. Meanwhile, test positivity is as high as 20% in Tennessee and Texas. It’s quite high in many other states as well (though not that high). This indicates that testing has not kept pace with community spread. We have more cases than we are currently capturing through testing.
5. Because of these trends, we can and should expect hospitalizations and deaths to continue to increase. Things will continue to get worse before they get better. Expect more grim milestones. That said, the actions we take can curb community spread. PLEASE do your part — wear your mask, wash your hands, keep 6+ feet apart, avoid crowds, closed spaces, and crowded places. And when it’s your turn, please get your vaccine.

Q&A for 1/12:

#Vaccination #Prioritization

Question: Based on Sunday’s post about lasting immunity, would it make sense to take into account previous COVID infection as we prioritize who gets the vaccine?

Answer: Given what we currently know about lasting immunity and what our vaccine distribution/administration experience has been to date, I do not think that adding another criterion for vaccine prioritization would be helpful. First, immunity post-infection may not be lasting at the individual-level (described further below). Second, vaccine distribution has already been challenging in the US with a great deal more vaccines distributed than administered. As of Monday, 25.5M vaccines were distributed of which 9M vaccines were administered across the country. Adding yet another criterion will further complicate the roll-out.

Not everyone agrees with my assessment (believe it or not)! I just read in the Washington Post this morning that Ireland is contemplating asking those who have been previously infected to wait to get the vaccine. In the context of limited vaccine supplies, this could make sense. But the WaPo article also quotes Boston University epidemiologist, Dr. Eleanor Murray, who states, “Confirming whether or not someone has had covid already adds an unnecessary layer of red tape onto vaccine prioritization. Given that the prioritization is designed to get vaccine first to those people who are most likely to get infected and/or get very sick from infection, it makes sense to reduce the barriers to vaccinating this group as much as possible,”

More on Lasting Immunity

The study from Science I cited on Sunday found huge heterogeneity among participants in terms of their immune memory. That to say — the study indicates that at a population level, immunity seems to be lasting for at least many months, but given differences between individuals, this effect may not hold at the individual-level. To de-prioritize folks who have previously been infected — especially folks who remain at higher-risk due to their employment, age, or underlying conditions — may unduly put them at risk of reinfection. Note: cases of reinfection remain rare at this point, but they are indeed possible (see Q&A of 11/21) .

Q&A for 1/11:

#Vaccination #Transmission #Protection

Question: Is anyone studying whether being vaccinated protects you from also carrying the virus? I am worried because pretty soon, a large contingent of adults will be vaccinated but our kids still won’t be. It would be nice to know if vaccinating someone also might confer a reduced risk to the kids in their household or classroom.

Answer: We do not yet know whether being vaccinated also protects you from being infected and contagious (see Q&A of 12/13 and more details below). Yes, studies are underway, but it will be some time before we have the results. Yesterday, Dr. Lena Wen answered a very similar question for CNN, explaining that “We don’t know if people who are vaccinated could still be carriers of the virus, even if they don’t get sick. That means you could be protected yourself if you get exposed to someone with coronavirus, but you could still be a carrier of the virus. When you get together with your loved ones, you could spread it to those who aren’t vaccinated.” A related article published earlier today in Quartz concludes, “it’s vital that even after receiving both doses of the Covid-19 vaccine, all individuals wear masks, practice physical distancing, and wash their hands when around those who haven’t been vaccinated — just in case.”

I was confused as to why the vaccine would be so effective at preventing disease but may not be effective at preventing infection and transmission. In that vein, I found the aforementioned Quartz article, Can you spread Covid-19 if you get the vaccine?, very informative. Basically, we know that the currently approved vaccines are really good at eliciting IgG antibodies, which quickly react to foreign invaders. However, we don’t know whether and how well the vaccines elicit IgA antibodies. IgG antibodies circulate in our blood and muscles and do not interact with the outside world, unlike IgA antibodies, which patrol outward facing mucosal surfaces — like the nose — and prevent foreign invaders from further entering the body. As I understand it, IgG antibodies go to work once the body is invaded whereas IgA antibodies keep the body from being invaded. Since we don’t know how the vaccines impact IgA antibody response, we don’t know whether vaccination prevents infection. Assuming that a vaccinated person can become asymptomatically infected, and since we don’t know how much of the SARS-CoV-2 virus is necessary to cause a new infection, we also don’t know whether vaccination prevents transmission. In heartening news, Emory University immunologist Matthew Woodruff tells Quartz, ““I can’t imagine how the vaccine would prevent symptomatic infection at the efficacies that [companies] reported and have no impact on transmission.”

Q&A for 1/10:

#Treatment #Immunity

Question: Got any good news?

Answer: Two studies were published in the last few days that offer some good news regarding effective treatment and lasting immunity:

1. Effective treatment: The New England Journal and Medicine published this week the results of a randomized controlled study, Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults, which showed that if given to older patients (ages 65+) early after symptom onset (within 72 hours), convalescent plasma (e.g. blood plasma from people already recovered from COVID) can significantly reduce the risk of severe disease (nearly halving the risk of severe respiratory disease; 48% relative risk reduction among treatment group compared with placebo group). Of the 80 participants who received convalescent plasma, 13 (16%) developed severe disease whereas of the 80 participants who received placebo, 25 (31%) developed severe disease. For this study, severe disease primary endpoints were defined as “a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both.”
2. Lasting immunity: Science published this week the results of a longitudinal cohort study, Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection, which studied SARS-CoV-2 immune memory — antibodies, memory B cells, CD4+ T cells, and CD8+T cells — over time among 188 participants who had recovered from mild, moderate, and severe COVID, including a few participants who recovered from asymptomatic infection. 51 participants provided blood samples at multiple time points, allowing for longitudinal study, and 43 participants provided samples >6 months after symptom onset. Researchers found that 5–8 months post-symptom onset, almost all individuals had SARS-CoV-2 antibodies; memory B cells were detected in almost all COVID-19 cases, with no apparent decline within 5 to 8 months post-infection; and memory T cells declined over time, but were comparable to levels observed after yellow fever immunization. Overall, the study shows that “durable immunity against secondary COVID-19 disease is a possibility in most individuals.”

Q&A for 1/9:

#Flu

Question: You showed a US flu map he other day, which was very green (minimal flu). I’m curious, how does the map compare with previous years?

Answer: The data I shared a couple of days ago was for end-December. We now have data for flu week 53, ending January 2nd, which shows that flu activity remains unusually low. For comparison purposes, Figure 1 includes the early-January 2021, 2020, 2019, and 2018 flu maps from CDC. The difference this year is amazing. Makes me think maybe we should wear masks every fall/winter flu season… but that’s just a hypothesis!

Figure 1. USA Influenza Map, early-January 2021, 2020, 2019, and 2018

Q&A for 1/8:

#Super-spreader

Question: What can we expect the fallout from Wednesday’s attempted coup with respect to COVID rates in DC? I know, you probably can’t publish that. But the sight of the maskless, lawless looters struck fear for both what they were doing to our democracy and what they’re doing to our health

Answer: First off, thanks to everyone for reaching out. We are lucky to work and school from home, so we are safe and hunkered in. I hope you readers are also safe, and I welcome you to share your perspectives with me if you’re so inclined. Like many of you, we’re angry. We demand accountability and arrests, a peaceful transfer of power to President-elect Biden, and an end to the racism that allows and promotes white insurrectionists to rampage our Capitol.

Back to the pandemic — Wednesday’s riot was a perfect storm for a super-spreader event — we witnessed people in closed spaces, crowded places, and close-contact settings, shouting and maskless. This is the exact type of event that could increase the spread of COVID not only in DC, but in all the places these people returned. Yesterday’s NY Times and a number of other news outlets published stories on this very matter. As the NY Times article, Experts say the Capitol Hill riot was probably a super-spreader event, stated “hundreds of rioters shouting in crowded rooms and hallways for extended periods of time can infect dozens of people at once.” This is especially concerning given the new, more contagious variants circulating.

Q&A for 1/7:

#Influenza #Trends

Question: I haven’t heard much about flu season recently. I remember that it was mild in the Southern Hemisphere. Is that the case for the Northern Hemisphere?

Answer: We last talked about influenza in our Q&A of 10/21, finding that seasonal influenza rates were low. Approximately 2.5 months later, influenza rates remain low. In this week’s influenza report, CDC states that flu activity in the US is “lower than usual for this time of year.” For week 52 (ending December 26th), 36,953 specimens were tested across the country, of which 76 (0.2%) were positive. As you can see in Figure 1, only one state has moderate flu activity, Mississippi. CDC also reports that “A total of 101 laboratory-confirmed influenza-associated hospitalizations occurring between October 1, 2020 and December 26, 2020 were reported by FluSurv-NET sites. This number is lower than average for this point in the season and comparable to counts seen at this point during the 2011–12 season.”

A number of studies have been published around the world examining influenza activity during the pandemic. Evidence continues to accumulate that non-pharmaceutical interventions (NPIs) — mask wearing, distancing, hand washing — are highly correlated with lower influenza rates (a few examples here, here, here, and here). One could also hypothesize that testing for influenza has been limited due to the pandemic, but even in Australia where flu testing increased in 2020 compared with previous years, influenza was much lower than previous seasons. One could also hypothesize that increased influenza vaccination has tamped down influenza rates. CDC reports that 192.3 million doses of influenza vaccine were distributed across the country as of 12/25, which is 17.8 million doses more than the 2019–20 flu season. However, a recent MMWR report found that “early-season data do not indicate substantial differences in intended influenza vaccination behavior during the 2020–21 influenza season compared with other recent seasons.” One positive of all the behavior change because of the pandemic is that influenza and other respiratory infections have become far more rare.

Figure 1. Influenza Map, December 26th (from CDC)

Q&A for 1/6:

#Doses #Vaccination

Reminder: you can find older posts at https://covidQandA.org

Question: There’s been a lot of discussion and perhaps pressure to extend the vaccination period between doses or even lessen the doses for optimal coverage. Did the 2-dose vaccine producers release any data about the effectiveness of their vaccines after a single dose? Would extending the period between doses or minimizing the second dose result in the drugs becoming less effective as the virus mutates, similar to our history with antibiotics or antimalarials?

Answer: We need to make evidence-informed, transparent decisions for best health outcomes and to bolster public trust. Moderna’s and Pfizer’s clinical trial results were based on a two dose regimen spaced 28 days/21 days, respectively. As Dr. Fauci told NBC last week, “If you want to stick with the data, that’s the way you should do it.” On this matter, my thoughts align with the FDA’s stance described in the FDA press release of 1/4 — “We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.”

Just today, The BMJ published a fantastic article that gives detailed answers to your questions, Covid-19 vaccination: What’s the evidence for extending the dosing interval? The article quotes Paul Bieniasz, a retrovirologist from Rockefeller University who stated, “My concern, as a virologist, is that if you wanted to make a vaccine-resistant strain, what you would do is to build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection.” It also provides a synthesis of the limited evidence on effectiveness of just one dose, reminding the reader that “Pfizer has said that it has no evidence that the protection [afforded by one dose] lasts beyond the 21 days.”

Finally, in the US our current problem isn’t a lack of vaccines; it’s overstretched local administration efforts. That’s the problem we need to be dealing with right now — we need more resources and support for local public health efforts to address vaccine hesitancy and get the vaccine administered (Health Force!). Read on for a few more details in response to your questions.

A bit more background: Last week, the UK announced a plan to delay the second dose of the Pfizer and AstraZeneka vaccines in order to get 1st doses out to more people. With limited vaccination supply and the virus surging, the UK’s rationale is that “Prioritising the first doses of vaccine for as many people as possible on the priority list will protect the greatest number of at-risk people overall in the shortest possible time…” The US is *not* following this approach. However, recognizing that the US has not yet been able to procure enough vaccines for the entire population, NIH and Moderna scientists have begun analyzing the data to see if they can double the supply of the Moderna vaccine by halving doses. Study results are expected in 2 months, and even if they are promising, they will still need to be reviewed and approved by the FDA, as reported yesterday in the NY Times. Meanwhile, as also reported by the NY Times, “Officials are rushing to find supplies of more efficient syringes that could extract an additional dose from vials of the Pfizer-BioNTech vaccine and bolster the Pfizer supply by 20 percent.”

Q&A for 1/5:

#Variant

Question: I’ve read that the new variant out of the UK is more contagious. What does that mean in practice? Does it just go from person to person faster or does an infected person pass it along to more people?

Answer: To my knowledge, we don’t know yet. It could be that an infected person sheds more virus, making it easier to pass on to others. It could be that the infectious period is different, making the timing of infection more speedy or making a person contagious for longer. It could also be that the virus is better at binding to cells. Lots of hypotheses. So far, all the research we currently have shows that it does not result in more severe disease (yay!), but because it is more transmissible, we can expect it to cause more infections, which will cause more hospitalizations and deaths (uggghhh!). Bulleted below is a summation of the pre-publication (not peer reviewed) findings that have been published in the last week, as well as a Public Health England update published a few days ago. You can also find a bit more background in our Q&A of 12/21 and these syntheses from Contagion Live and WHO are both very informative.

• Public Health England Investigation of novel SARS-CoV-2variant: Technical Briefing 2 (published 12/28): This overview of the variant in the UK includes data on outcomes of a matched cohort study comparing outcomes of those hospitalized with the preexisting variant and new variant. Findings show that 28-day case fatality rates were not statistically significantly different between the two groups, indicating that the variant does not cause more severe disease. Researchers also examined whether reinfection was more likely with the variant, but found no statistically significant difference. Finally, researchers used contact tracing data and found that a higher percentage of contacts of those with the variant themselves became infected (15.1% of new variant contacts vs. 9.8% of preexisting variant contacts).
• Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England (posted on medRxiv on 12/26): Researchers use a transmission dynamic model to estimate that the variant is “56% more transmissible (95% credible interval across three regions 50–74%) than preexisting variants of SARS-CoV-2.” This finding is consistent with other research indicating the variant is 70% more transmissible. Researchers find no evidence that the new variant results in greater/lesser disease severity.
• S-variant SARS-CoV-2 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-QPCR (posted on medRxiv on 12/27): Researchers used a dataset of positive test results based on a test that can differentiate between the existing and new variant and found that viral load among those with the new variant was generally higher, which could have implications regarding transmissibility.
• SARS−CoV−2 Variant Under Investigation 202012/01 has more than twofold replicative advantage (posted on medRxiv on 1/4): Researchers use data from GISAID to estimate the replicative advantage of the new variant compared with preexisting variants. They find the replicative advantage is 2.24 [95% CI: 2.03−2.48], stating that “such significant replicative advantage and the fact that London serves as major international transportation hub suggest that the VUI−202012/01 strain will likely become globally dominant, hindering containment of the COVID−19 epidemics prior to massive vaccinations.”

Q&A for 1/4:

#Deaths #Age

Question: So I’ve read that 1/1000 Americans has died from COVID. Can we get a new breakdown of the ages of those that have died?

Answer: According to the CDC, as of yesterday a total of 349,246 individuals have died of COVID in the US. With the overall US population at 331 million, the estimate you read is correct — to date, 0.1% or 1 of every 1,000 of us has succumbed to COVID. You can find basic demographics related to cases and deaths at CDC’s COVID Data Tracker, which I’ve used to pull the deaths by age data included in Figure 1 below. Deaths increase with age; no age group has been spared; deaths among children are rare.

Note: data presented below are for 249K deaths, and are about 6 weeks behind due to reporting lags.

Figure 1. COVID Deaths by Age

Q&A for 12/23:

#Vaccination #Timeline

Note: Happy Holidays! Merry Christmas! Happy New Year! I’m taking a break from the daily Q&A from 12/24 through 1/3. If you have a question, go ahead and send it and I’ll aim to respond when I resume posts in the new year. Take care, everyone!

Question: When can we expect the vaccine priority Phase 1b group to begin to get immunized?

Answer: Likely by late-January. Yesterday, CDC released The Advisory Committee on Immunization Practices’ Updated Interim Recommendation for Allocation of COVID-19 Vaccine, which confirms that “In Phase 1b, COVID-19 vaccine should be offered to persons aged ≥75 years and non–health care frontline essential workers, and in Phase 1c, to persons aged 65–74 years, persons aged 16–64 years with high-risk medical conditions, and essential workers not included in Phase 1b.” It also offers a helpful table on how many people are in each category (Table 1). As you’ll see, 24 million health care personnel and long-term care facility residents are in Phase 1a.

There’s no set date for when we move to Phase 1b. And as of yesterday, according to Bloomberg News, 777,766 doses had been administered since the initial roll-out on 14 December. The daily number vaccinated is increasing with increased distribution, especially thanks to the Moderna vaccine authorization/roll out. According to data from CDC, Operation Warp Speed allocated enough Pfizer vaccination doses as of 12/23 to cover 7.658 million people (1st and 2nd doses) and enough Moderna vaccination doses to cover 7.995 million people (1st and 2nd doses). If things continue at this pace, we would expect to have enough Pfizer and Moderna doses allocated to cover the full 24 million Phase 1a population by early January. Add to that the time to get the vaccines to administration sites plus the time to get the vaccines administered and we’re probably looking at Phase 1b starting in late-January across most of the country. Indeed, this is what New York State’s Governor Cuomo described as its expected timeline (note: in NYS, Phase 1b is called Phase 2).

Table 1. Prioritized Vaccine Group Population Size (millions) (from CDC)

Q&A for 12/22:

#Seroprevalence

Question: The other day, I heard that 1 in every 100 Nashvillians is currently infected. That got me to wondering, what proportion of Tennesseans have likely been infected to date?

Answer: To my knowledge, we don’t have a good *current* estimate. As of September, our best estimate is that ~7% of Tennesseans had SARS-CoV-2 antibodies indicating previous infection.

Recognizing that testing hasn’t captured everyone who has been infected, CDC is leading three types of seroprevalence surveys to estimate the proportion of the population that has been infected — large-scale geographic surveys, community-based surveys, and special population surveys. Last month, JAMA published the latest results (September) from the large-scale survey, Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020. As of 24 September, researchers estimate that ~7% of Tennesseans had been infected. You can see the seroprevalence estimates for Tennessee and other states in Figure 1. To put things in perspective, after the height of New York’s initial wave, the survey estimated that ~23% of New Yorkers had antibodies.

This survey has important limitations, a big one being that because it analyzes blood specimens collected for routine health screenings, its results may not be representative of the general population. Additionally, we’ve seen a huge wave of new cases since September, so these estimates are most surely out of date. And since antibodies may wane over time, these surveys may underestimate rates of prior infections. Finally, if you want to read more about seroprevalence in other countries as of September, this paper gives a nice synthesis — Population-based seroprevalence surveys of anti-SARS-CoV-2 antibody: An up-to-date review.

Figure 1. Seroprevalence estimates by state over time (JAMA)

Q&A for 12/21:

#Mutation

Question: I was listening to the news about the new virus strain in the UK. Where did the mutations come from?

Answer: There is currently no data on the precise nature of the event(s) that led to the new variant. The current hypothesis is that the new variant came from a chronically infected individual who was likely immunocompromised. Basically, the idea is that the virus adapted within a patient as the virus was faced with different pressures inside the body — weakened immune system allowing the virus to persist plus convalescent plasma treatment (antibody therapy) pushing the virus to adapt. This hypothesis is further described in the COVID Genomics UK Consortium’s preliminary analysis, “Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations.”

Consortium scientists write that this variant (B.1.1.7) carries “an unusual number of virus genetic changes” (17) that is “unprecedented” since circulating SARS-CoV-2 lineages generally accumulate no more than 1–2 mutations per month. Scientists hypothesize that “the unusual genetic divergence of lineage B.1.1.7 may have resulted, at least in part, from virus evolution with a chronically-infected individual.” Many questions abound. If you’re interested in reading more, but not keen on reading the Consortium’s report, the BBC published a helpful synthesis yesterday, “New coronavirus variant: What do we know?”

Q&A for 12/19:

#Priority Populations #Vaccination

Note: I will be away from my computer most of Sunday. Q&A will resume on Monday.

Question: Can this be right? I was reading on CNN that “The CDC estimates there are 21 million health care personnel, 3 million long-term care residents, 87 million essential workers, 100 million adults with high-risk medical conditions and 53 million others 65 and older.” This is saying 264M people fall into some type of priority group. There’s only 330M people in the US, and 74M of the US population is children. Seems like there’s some double counting in these groupings.

Answer: You’re right. There’s double and triple counting going on here (Figure 1). The challenge is that — to my knowledge — we don’t really have a good estimate of the overlap because we don’t have a good way to disaggregate the data. We have to look to multiple different data sources. For example, as of 2018, 64% of US adults ages 65+ had two or more chronic conditions (~34M). Meanwhile, nearly 1/3 of the nation’s physicians are ages 60+ (totaling >290K) and according to research using the American Community Survey published earlier this year in JAMA, ~500K healthcare workers, including physicians, are ages 65+. Estimates of essential workers vary in size depending on the data source used. In addition to CDC’s 87 million estimate, I’ve also seen estimates as low as 55 million and as high as 101 million. The essential worker category includes all healthcare personnel. It’s also estimated that about 8% of essential workers are ages 65+ (Table 1).

Figure 1. Phase 1 Vaccine Prioritized Groups (from ACIP Slides)

Table 1. Essential Worker Characteristics (from JAMA, Economic Vulnerability of Households With Essential Workers)

Q&A for 12/18:

#Ivermectin #Treatment

Question: A guy in my men’s group seems to be swayed by a video of Dr. Pierre Kory at the U.S. Senate talking about ivermectin last week. I sent him your previous post and this is what he responded (main points copied below). Anyway, do you have anything further to say in regards to the video and study? Portions of his response: “What caught my attention with Dr. Kory’s testimony is his description of the Brazil study that had just come out. In it, 800 health workers were studied with 400 receiving ivermectin and 400 not. He reported that not one of those receiving the drug contracted the disease while, of those not receiving it, 58% contracted it. He also refers to I believe 30 other studies. While this info is what I’m going on and believing in, everyone, of course, needs to make their own determination. I’m requesting a prescription from my doctor!”

Answer: The evidence we have to date is not strong enough to make sweeping determinations about the effect of ivermectin as treatment or prophylaxis. The danger of jumping to conclusions too quickly is that it can put individuals and populations at risk of adverse outcomes. We don’t have enough information to know whether ivermectin works, what dose would be the safest and most effective to prevent/treat COVID-19, and whether there are any serious concerns related to ivermectin’s interactions with other drugs or viruses. When a medication is used for approved indications, its health risks are generally predictable, but when used for a new indication (off-label), the medication’s health risks and effectiveness are unknown. If you want to protect yourself, the best thing you can do is to wear your mask, keep your distance, wash your hands, avoid the 3Cs — closed spaces, close-contact settings, crowded places, and get the vaccine when it’s your turn! Read on for my take on Dr. Kory’s testimony.

I read Dr. Kory’s testimony and didn’t see any data on Brazil. I also didn’t find anything in my quick search of the peer reviewed literature (pubmed.gov) or on clinicaltrials.gov (search terms: ivermectin, covid19, Brazil). Regardless, I know that his testimony made a lot of waves and that he presented data from several other studies based on his team’s synthesis of 21 ivermectin studies, all of which he reported “show positive results.” In my quick review of the published literature, I found several peer-reviewed studies that indicated positive results (a couple of examples here, here) but I also found several peer-reviewed studies that were not positive (links here, here, and here). I raise this issue not because I have a stake in whether ivermectin is good or bad (I hope it works!), but to highlight that there seems to be some bias in the studies that Dr. Kory included in his synthesis. Among the studies he does cite, there are methodological limitations that make drawing conclusions like, “I’m requesting a prescription from my doctor!” problematic. The clinical blog, REBEL-EM, provided a really thorough review of several key ivermectin studies in its post of 12/16, COVID-19 Update: Ivermectin, concluding “Ivermectin is interesting, there is certainly signal to evaluate further, but in our desire to want a treatment option, let’s not continue to do the same thing over and over again, as we saw play out with Hydroxychloroquine.” Remember our experience with hydroxychloroquine? Higher doses were associated with cardiac arrest. Some studies even indicated that treatment with hydroxychloroquine was associated with worse outcomes among COVID-19 patients, including longer hospital duration and increased risk of death. Again, jumping to conclusions too quickly can put individuals and populations at risk. If you want to do something, mask up! And when it’s your turn, get the vaccine! Finally, if you want to read more, this recent COVID-19 treatment ethics paper is an informative read.

Q&A for 12/17:

#Vaccines #Messaging

Question: One question I keep getting (from my public health and non public health friends alike) is, ‘why should I trust that the vaccine is safe to take for myself and my loved ones.’ I feel that there is an urgent need for a list of consistent, concise messaging that (public health practitioners, politicians, community leaders) can use to explain to the general public why they should be the first to line up to take this vaccine. Would you please synthesize some key messages?

Answer: We’ve talked about vaccines a lot over the past month, but I’ve tried to provide much of this messaging alongside the science, which means that the messages have not been brief! Here is a synthesis of some of those key messages. Two important notes: 1) Messaging needs to be tailored to the audience!; 2) Please rely on other public health resources to bolster your messaging. CDC just began to offer a vaccination communication toolkit and CDC’s mRNA healthcare provider resources.

Scientific rigor:

• All necessary scientific steps have been taken to ensure the vaccines work without detrimental health impacts. (Q&A of 12/16)
• Like all vaccines, COVID-19 mRNA vaccines have been rigorously tested for safety before being authorized for use in the United States. (CDC)
• mRNA technology is new, but not unknown, having been studied for more than a decade. (CDC)

mRNA safety:

• mRNA vaccines do not contain a live virus and do not carry a risk of causing disease in the vaccinated person. (CDC)
• mRNA vaccines do NOT interact with a person’s DNA and are unable to affect or change a person’s DNA. (Q&A of 12/5)

Side effects:

• Several non-serious side effects are common but short in duration, including pain at injection site, fatigue, and headache. (Q&A of 12/16)
• Serious adverse events are rare. (Q&A of 12/16)
• Adverse events linked to vaccination generally start within 6 weeks. (Q&A of 12/16)
• CDC will lead ongoing safety monitoring as the vaccine is rolled out. (CDC)

Prioritization:

• While production, manufacturing, and distribution ramp up, vaccine supply will be limited. (Q&A of 12/9)
• Those first in line to receive the vaccine are health workers and residents of long-term care facilities. (Q&A of 12/9)
• Next in line will be frontline workers, followed by those with underlying conditions, and those ages 65+. (Q&A of 12/9)
• It will be many months into 2021 before for children and the general population will be eligible for the vaccine. (Q&A of 12/9)

Outstanding questions:

• There are still a number of outstanding questions that scientists are working to answer. (Q&A of 12/13)
• Does the vaccine prevent infection?; Does the vaccine prevent transmission?; How long does immunity last?; How well does the vaccine work among some high-risk populations?; How well does the vaccine work among children? (Q&A of 12/13)

Q&A for 12/16:

#Vaccines #Side Effects #Serious Adverse Events

Question: Now that the first of the vaccines is becoming available in the U.S., can you summarize what we know and don’t know about the vaccines’ safety? How were the clinical trials processes applied for these vaccines (Pfizer, Moderna, AstraZeneca, others?)? What incidents occurred during these trials? What is the probability of experiencing side effects or adverse reactions? What types of side effects are associated with the vaccine at time of vaccination? Later on?

Answer: So many related questions! I’m going to focus answers on the Pfizer and Moderna vaccines since they are moving forward more quickly than others with more detailed information available, especially related to side effects. Information included herein is pulled largely from: FDA review of the Moderna vaccine, FDA review of the Pfizer vaccine, and the peer reviewed Pfizer study recently published in the New England Journal of Medicine, Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine (Figure 1).

Vaccine Development: All SARS-CoV-2 vaccine candidates have followed the same basic process — cell culture study, animal study, small human trial, large human trial (see Q&A of 5/13). At each step, safety and efficacy is assessed. If serious adverse events occur at any step, the study is halted. Loads of vaccine candidates don’t ever make it to market due to safety concerns and/or lack of efficacy. And even after a vaccine is authorized/approved, safety continues to be monitored (described in Q&A of 7/22). When it comes to large-scale human trials, scientists use the randomized control trial (RCT) study design, which allows them to compare what happens to people who receive the vaccine with those who receive a placebo. Pfizer and Moderna both employed RCT for their large-scale human studies.

Serious Adverse Events: Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt. Pfizer and Moderna data span 2 months after the 2nd vaccine dose, so we have a pretty good idea of their safety profile. For both vaccines, serious adverse events are rare.

• As reported in the NEJM, “Four related serious adverse events were reported among BNT162b2 [Pfizer vaccine] recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the vaccine or placebo.”
• And as reported by the FDA’s review of Moderna, “13 deaths were reported (6 vaccine, 7 placebo)… These deaths represent events and rates that occur in the general population of individuals in these age groups…. Among participants who received at least one dose of vaccine or placebo (N=30,351), the proportion of participants who reported at least one serious adverse event from dose 1 to the primary analysis cutoff date (November 25, 2020) was 1% in the mRNA-1273 group and 1% in the placebo group.”

Side Effects: Though serious adverse events are rare, several non-serious side effects are common:

• FDA writes of the Pfizer vaccine, “The most common solicited adverse reactions were injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%)…. Among non-serious unsolicited adverse events, there was a numerical imbalance of four cases of Bell’s palsy in the vaccine group compared with no cases in the placebo group, though the four cases in the vaccine group do not represent a frequency above that expected in the general population.”
• FDA writes of the Moderna vaccine, “The most common solicited adverse reactions associated with mRNA-1273 were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%)… lymphadenopathy (axillary swelling and tenderness of the vaccination arm) was reported as an unsolicited event in 173 participants (1.1%) in the vaccine group and 95 participants (0.63%) in the placebo group… there were three reports of facial paralysis (Bell’s palsy) in the vaccine group and one in the placebo group. Currently available information is insufficient to determine a causal relationship with the vaccine.”

Figure 1. Pfizer Research Summary (from NEJM)

Q&A for 12/15:

#Genes

Question: The other day, I listened to a BBC report on genetic studies relating to who gets very sick with COVID. The study identified a gene that supposedly could indicate if a COVID patient will get worse or better. At least this is how I understood the reporting. The study only focused on COVID positive cases so this is not about natural gene immunity to COVID. I was wondering if you have seen similar studies or heard of them and what is your opinion and how it could be used to determine whether positivity will result in hospitalization. Right now we are looking at positivity to implement restrictions but if we were able to narrow the percentage of those positive who will end up in hospitals, wouldn’t that be useful as a measurement?

Answer: I think the BBC report you’re referring to is this one, Covid: Genes hold clues to why some people get severely ill, which is reporting on a study published a few days ago in Nature, Genetic mechanisms of critical illness in Covid-19. The study findings are especially useful for identifying potential therapeutic advances. Since we’re not at the stage of gene-based personalized medicine, this type of study is *not* useful for identifying whether a given individual is at risk of severe COVID. Read on for more background and a brief description of the study.

The Strangeness of COVID-19: During a CSIS event yesterday, Dr. Fauci described SARS-CoV-2as “one of the most, if not the most, unusual virus that any of us have ever dealt with. Certainly in my 36 years as director of the institute I have not seen anything where you have a virus that in the — in 40 percent of the people has no symptoms. Then those who have symptoms, 80 percent have very mild to moderate symptoms that don’t require any significant medical intervention. And then you have 20 to 25 percent of people who are devastated, at attests the almost 300,000 deaths. There’s something very strange about a virus that in most people barely bothers them and in others it kills them. We still don’t understand why that’s the case right now.”

Genetic Susceptibility to Severe Illness: Genetic susceptibility is one of the theories to account for the strangeness of COVID-19, in terms of both susceptibility to viral infection and propensity to develop severe illness (e.g. harmful lung inflammation). As described and well referenced in the background section of the Nature paper, “Susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable. In particular, susceptibility to respiratory viruses such as influenza is heritable and known to be associated with specific genetic variants. In Covid-19, one genetic locus, in 3p21.31, has been repeatedly associated with hospitalisation.”

Study Purpose: If we can identify the genes connected with severe illness, we can find therapies to improve immune response and save lives!

Study Methods: The GenOMICC (Genetics Of Mortality In Critical Care, genomicc.org) study has been recruiting patients with critical illness syndromes, including influenza, sepsis, and emerging infections, for 5 years. Researchers performed a genome-wide association study comparing critically ill patients with Covid-19 with controls from population genetic studies in the UK. The analysis included 2244 individuals with severe COVID-19. These individuals were matched with controls based on common ancestry (5 controls to 1 case). Controls were excluded if they had a known positive test for the novel coronavirus.

Study Findings: Findings reveal that COVID-19 critical illness “is related to at least two biological mechanisms: innate antiviral defences, which are known to be important early in disease (IFNAR2 and OAS genes), and host-driven inflammatory lung injury, which is a key mechanism of late, life-threatening Covid-19 (DPP9, TYK2 and CCR2).” Study authors go on to describe how these findings relate to various therapeutics.

Other Genetic Studies: There are a number of other studies that have looked at the relationship of various genes to susceptibility to infection and to severe illness. One set of studies we’ve talked about in the past is about the relationship of blood type and susceptibility (see Q&A of 10/15). Interestingly, this latest study’s findings indicate that the ABO locus (genetic basis for blood type) may be associated with susceptibility to infection, but is not associated with critical illness.

Q&A for 12/14:

#Isolation

Question: A friend of mine got a Covid test after experiencing mild cold symptoms because he is 70 and has RA. His test was positive. He took a second test a week later (around 4–5 days ago after no longer having symptoms and his test was positive again (got results 2–3 days ago). He is thinking he can leave quarantine because his symptoms have been gone for over 10 days. Is this correct, even though he tested positive again?

Answer: Your friend is correct! CDC recommends using a symptoms-based strategy to end self-isolation (Table 1). From your description, it sounds like your friend meets all the criteria — his illness was not severe and he is not severely immunocompromised, it’s been at least 10 days since symptoms began, he’s gone at least 24 hours fever-free without fever-reducing medication, and his symptoms have improved (he doesn’t even have symptoms anymore!). The reason that we don’t rely on tests to end isolation is that PCR tests in particular can pick up virus remnants for a long time, much longer than a person is infectious. If we relied on a test-based strategy to end isolation, folks would be isolating for much longer than necessary. For more background on this testing issue, check out our Q&A of 10/24.

Table 1. Symptoms-based Strategy to End Isolation (from CDC)

Q&A for 12/13:

#Vaccine #Infection #Illness

Question: One of my friends told me that while studies have shown that the Covid vaccines are effective in preventing a vaccinated individual from getting sick with Covid, it is currently unknown whether or not a vaccinated individual can still get and shed the virus — potentially transmitting the virus to other, unvaccinated individuals. Is this accurate?

Answer: Your friend is correct. The Pfizer, Moderna, and AstraZeneca trials are primarily aiming to understand whether the vaccine protects against illness (COVID-19). For example, the Pfizer trial’s main endpoint is cases confirmed ≥7 days after Dose 2 — with a case defined as a positive virologic test plus at least one COVID-19 symptom (e.g. symptomatic cases). The initial data we’re seeing from all three vaccine trials is a resounding yes — these vaccines can prevent illness! That’s so exciting, but many questions remain*, including whether the vaccines can prevent infection:

1. Does the vaccine prevent infection? Secondary efficacy endpoints vary by study, with Moderna and AstraZeneca also examining whether the vaccine prevents infection. The Pfizer trial does not include this secondary endpoint. As FDA wrote in its review of the Pfizer vaccine, “Data are limited to assess the effect of the vaccine against asymptomatic infection… Additional evaluations will be needed to assess the effect of the vaccine in preventing asymptomatic infection, including data from clinical trials and from the vaccine’s use post-authorization.”
2. Does the vaccine prevent transmission? More data is required. As FDA writes in its review of the Pfizer vaccine, “Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination. Demonstrated high efficacy against symptomatic COVID-19 may translate to overall prevention of transmission in populations with high enough vaccine uptake, though it is possible that if efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission.”
3. How long does immunity last? So far, we have solid data from the Pfizer vaccine that immunity lasts at least two months (length of the current analytic period). For the current randomized control trials, Pfizer and Moderna plan to follow participants for 2 years after the second dose while AstraZeneca plans to follow participants for 2 year after the second dose.
4. How well does the vaccine work among some high-risk populations? While high risk populations are included in the vaccine trials, some groups may be represented in too small numbers to draw conclusions (see Q&A of 12/10)
5. How well does the vaccine work among children? For the Pfizer vaccine, we cannot extrapolate to children <16 years of age. Expansion of trial to younger ages and ongoing data collection among children ages 12+ will fill these knowledge gaps. (see Q&A of 12/9)

*For the longer list of outstanding questions, see pages 46–28 of FDA’s review of the Pfizer vaccine.

Q&A for 12/12:

#Treatment #Ivermectin

Question: I got this note from a doctor at my daughter’s elementary school recommending that we all follow the “I-MASK+ protocol for COVID prophylactic and treatment.” The doctor went on saying that he and his wife are “taking the prophylactic ivermectin as it’s been shown to prevent transmission, and recommending everyone to do so at this point.” Is this quackery?

Answer: Yes, this ivermectin recommendation is quackery. Science is a step-by-step process. If you jump too far ahead of the evidence to form conclusions, you can do great damage, including by exposing people/patients to drugs/treatments that have detrimental effects. Self-medicating with a new drug can be really dangerous (ex: drug-drug interactions can be dire)! That’s why it’s so important to base medical guidelines on our best science. It’s also why we should never recommend that people self-medicate with a drug that is new to them and unproven for the purpose. I’m not saying this to put the kibosh on our study of ivermectin. We absolutely should be (and are) studying ivermectin as a potential COVID treatment — clinical trials will give us the data we need to develop the best treatment guidelines. Until we have that solid evidence base, please avoid the type of “medical guidance” your daughter’s school doctor shared. Read on for more information about ivermectin and COVID-19.

1. Safety/efficacy are unknown. The National Institutes of Health COVID Treatment Guidelines Panel “recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial.” The Food and Drug Administration (FDA) warns against ivermectin use, including for COVID prophylaxis, stating “Any use of ivermectin for the prevention or treatment of COVID-19 should be avoided as its benefits and safety for these purposes have not been established. Data from clinical trials are necessary for us to determine whether ivermectin is safe and effective in treating or preventing COVID-19.”
2. Approval is not granted. Ivermectin is used in tabular form to kill parasites and in topical form to stop diseases like scabies. While it is FDA-approved as an antiparasitic drug, it is not approved for treatment of any viral infection. Scientists have yet to find evidence in animal studies or human trials that it can treat viral diseases.
3. Side effects can be severe. As FDA also states, “Some of the side-effects that may be associated with ivermectin include skin rash, nausea, vomiting, diarrhea, stomach pain, facial or limb swelling, neurologic adverse events (dizziness, seizures, confusion), sudden drop in blood pressure, severe skin rash potentially requiring hospitalization and liver injury (hepatitis). Laboratory test abnormalities include decrease in white cell count and elevated liver tests.”
4. Dosage required is huge. While ivermectin has been shown to inhibit SARS-CoV-2 replication in cell cultures (lab studies), the amount of ivermectin needed to inhibit SARS-CoV-2 in the human body is estimated to require doses up to 100-fold higher than those approved for use in humans.
5. Doctor touting ivermectin has been debunked. One of the leaders of the “I-MASK+ protocol” is Dr. Paul Marik, who has a reputation for inappropriately elevating small, observational studies as revolutionary scientific advances. For example, Dr. Marik is known for having developed a treatment for sepsis based on a very small retrospective study of 47 patients. Over the last several years, across the lay press and medical education blogs he has promoted his treatment as the definitive. The findings — that a cocktail of vitamin C, corticosteroids and thiamine would dramatically reduce sepsis in ICU patients — were recently refuted thanks to a randomized control trial, results from which were published in JAMA earlier this year.

If you’d like to read more about ivermectin, here are a few more informative resources:

• NIH COVID Treatment Guidelines: Ivermectin
• FDA Ivermectin FAQ
• Pan American Health Organization: Ivermectin Recommendations
• Associated Press Ivermectin Fact Check
• NY Times Coronavirus Drug and Treatment Tracker
• Nature article, “Latin America’s embrace of an unproven COVID treatment is hindering drug trials”

Q&A for 12/11:

#ICU #Hospital #Capacity

Question: How full are ICU’s normally (before COVID)? It was my understanding that in order for hospitals to make enough money, they usually kept their beds, including ICU beds, close to full most of the time. While it’s clearly upsetting that they are now mostly COVID patients instead of elective surgeries, is it really abnormal for hospitals to have ICU’s at or near capacity?

Answer: Good question! ICU capacity typically averages 68%, ranging from 57% to 82%. We know this with such specificity thanks to rigorous research published a few years ago in Critical Care Medicine, ICU Occupancy and mechanical ventilator use in the United States. The study found that ICU occupancy varied considerably, but on average about 1/3 of ICU admissions were discretionary. For example, an average of 18% of ICU patients were admitted directly after elective surgery. Another study published earlier this year, Cancellation of Elective Surgery and Intensive Care Unit Capacity in New York State: A Retrospective Cohort Analysis, concluded, “Patients undergoing elective surgery comprised a small fraction of ICU bed and mechanical ventilation use in New York State….Suspension of elective surgeries may have a relatively minor impact on ICU capacity.” Upshot here is that on average (with big variation) ICUs have 7 in 10 beds occupied. Cancelling elective surgeries could free up another bed, giving ICUs a bit more slack (guesstimate average: ~4 open beds out of every 10).

The problem with ICU capacity is that even if you add beds and other equipment, you need the personnel to care for these very sick patients. And with the pandemic raging across the country, that slack just isn’t there. STATNews ran a good article on this issue back in August, ICU capacity is more about the clinicians than the number of beds and the NY Times had an informative article about the current state of affairs earlier this week, “‘There’s No Place for Them to Go’: I.C.U. Beds Near Capacity Across U.S” (Figure 1). Along with increasing ICU occupancy, another concerning trend has arisen. As recently reported in The Atlantic and the Washington Post, hospitalization rates are dropping. As public health expert, Dr. Ashish Jha states in the Atlantic and writes in the Post, “As hospitals fill up, they are admitting fewer and fewer people… as the demand for beds soars, the threshold for admission rises with it.” In summation, the ICU occupancy we’re seeing and experiencing across large swaths of the country is indeed abnormal.

Figure 1. Mapping ICU Occupancy (Dec. 9, NY Times)

Q&A for 12/10:

#Vaccination #Underlying Conditions

Question: My 28 year old daughter is a frontline worker at a state hospital and is being offered the opportunity to get the Pfizer vaccine next week. Because she has Sjogrens syndrome, we would like to know if there are any contraindications for receiving the vaccine. Were any people with Sjogrens included in the trials? Is there any available data regarding autoimmune disorders? Getting the vaccine sounds ideal, but should it be of concern for someone with Sjogrens?

Answer: Recurring reminder — I am not a medical doctor and your daughter should consult her medical doctor. Now, here’s what I know!

Pfizer Trial

The Pfizer trial included 43,538 participants with diverse backgrounds, including 7,623 individuals with underlying conditions (comorbidities). No serious safety concerns were observed, and the vaccine was found efficacious across age, sex, racial and ethnic groups, and participants with medical comorbidities. Unfortunately, safety/efficacy data on immunocompromised individuals — like people with Sjogrens syndrome — are too limited to draw conclusions. FDA issued its review of the Pfizer vaccine on Tuesday and is meeting today to discuss the emergency use authorization. In its written review, FDA states, “There are currently insufficient data to make conclusions about the safety of the vaccine in subpopulations such as children less than 16 years of age, pregnant and lactating individuals, and immunocompromised individuals.” Pfizer is planning to conduct ongoing studies to understand outcomes in diverse populations, including immunocompromised, pregnant, and very elderly (>85 years of age) individuals. Now the question becomes — Which is more risky for your daughter, taking the vaccine next week or waiting?

Benefits/Risks

Taking the vaccine earlier means that she benefits from the protection it affords from COVID-19 and potentially benefits others (if her experience adds to the safety/efficacy data; if the vaccine minimizes transmission risk to others). It also means that she misses out on the increase in knowledge on safety/efficacy in immunocompromised individuals that time/ongoing data collection affords. Taking the vaccine later means that she benefits from increased knowledge of vaccine safety/efficacy among immunocompromised individuals, but she continues to be at risk of infection and those who are immunocompromised may be at risk of severe illness from COVID-19 (per CDC).

Background Knowledge

Since the Pfizer vaccine is an mRNA vaccine (see Q&A of 12/5), it does not have any live, attenuated virus or bacteria; those live attenuated vaccines are the ones that have been met with complications among immunocompromised individuals. As ACIP earlier stated (2013) regarding other vaccines, “All inactivated vaccines can be administered safely to persons with altered immunocompetence.” CDC also has overarching guidelines for immunization of healthcare workers, which state, “A physician must assess the degree to which an individual health-care worker (HCW) is immunocompromised. Severe immunosuppression can be the result of congenital immunodeficiency; HIV infection; leukemia; lymphoma; generalized malignancy; or therapy with alkylating agents, antimetabolites, radiation, or large amounts of corticosteroids. All persons affected by some of these conditions are severely immunocompromised, whereas for other conditions (e.g., HIV infection), disease progression or treatment stage determine the degree of immunocompromise. A determination that an HCW is severely immunocompromised ultimately must be made by his or her physician. Immunocompromised HCWs and their physicians should consider the risk for exposure to a vaccine-preventable disease together with the risks and benefits of vaccination.”

Q&A for 12/9:

#Vaccination #Children

Question: I have two middle schoolers. In terms of COVID vaccine, would they need to wait until pediatric tests/trials are completed? They received the “adult” flu vaccine, just like me.

Answer: Children’s immune systems differ from adult’s systems, so it’s especially important to understand the degree to which a new vaccine impacts children through rigorous safety and efficacy evaluation. Your middle schoolers will not be eligible to receive the vaccine until vaccine safety/efficacy data for their age-group have been reviewed and the FDA has provided emergency use authorization (EUA). Even with authorization, it may still be some time before your kids receive the vaccine due to limited supply and vaccine prioritization. When it comes to your experience with influenza vaccine, the reason that they can receive the “adult” flu vaccine is because it has been proven safe and effective for them thanks to years of scientific research. Read on for a bit more on timeline, priority populations, and the influenza vaccine.

Safety/efficacy data timeline: Pfizer expanded its trial participation to include those ages 12+ back in October (see Q&A of 11/10) and expects to have data from those ages 12–17 in a few weeks (per Pfizer call I was able to participate in yesterday). Pfizer is developing its pediatric study plan and hopes to receive FDA approval to begin implementation soon (after safety/efficacy is proven for older children). Meanwhile, Moderna announced last week plans to expand its vaccination trials to those ages 12–17, but according to clinicaltrials.gov, the study is not yet recruiting.

Priority populations: The Advisory Committee on Immunization Practice (ACIP) issued its recommendations on Phase 1A priority populations last week and CDC adopted these recommendations as guidance. It is, however, up to each state to develop its own prioritization. ACIP has also shared its initial thinking on prioritized Phase 1 populations in publicly available slides from its November meeting. As Table 1 shows, after healthcare personnel and long-term care facility residents, the next prioritized population is essential workers, followed by adults with high-risk medical conditions and adults ages 65+. It will be quite a long time (many months into 2021) for children (who we still need safety/efficacy data for) and the general population to be eligible for the vaccine. If you’re curious about where you may be in the line, the NY Times offers this data visualization, Find your place in the vaccine line.

Influenza vaccine: CDC recommends that “all persons aged ≥6 months who do not have contraindications should be vaccinated annually.” The dosing varies by age and influenza vaccination history. Those ages 9+ requiring only one dose of influenza vaccine. There are several types of influenza vaccines, some of which are the same for adults and children, and some of which are intended for those ages 18+ or 65+ (see MMWR Table 1). The history of influenza vaccination in children is a long one that is well described in this article published back in 2013 in the Journal of the Pediatric Infectious Disease Society, Overview of Influenza Vaccines in Children.

Table 1: ACIP Proposed Phase 1 Sequence

Q&A for 12/8:

#Dead body #Risk #Funeral

Question: Morbid question, how long is someone who passed on contagious?

Answer: There is currently no evidence of transmission of SARS-CoV-2 through handling of bodies of deceased persons. While absence of evidence is not evidence of absence, there is believed to be little risk of contracting COVID from a dead body since the virus is primarily spread through respiratory droplets. Because scientists have found the virus in other bodily fluids (beyond respiratory droplets) and because the virus may live on surfaces for short periods of time, if you are around the body of someone who died of COVID-19, you should avoid touching the body, if possible. And if you need to touch the body, you should wear personal protective equipment (including gloves) and wash thoroughly thereafter. Figure 1 from CDC describes the differences in burial practices between COVID-19 and Ebola. I’m sharing it here because the COVID-19 portion offers sound advice. Of course, advice for different types of health workers and funeral workers is more stringent as these workers are more likely to be exposed to the bodily fluids of the deceased person, which carries more potential risk. If you want to read more, these resources are all very informative:

• WHO’s Infection prevention and control for the safe management of a dead body in the context of COVID-19: Interim Guidance
• CDC’s Funeral Guidance for Individuals and Families
• the European CDC’s Considerations related to the safe handling of bodies of deceased persons with suspected or confirmedCOVID-19
• BMJ Global Health’s Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review

Figure 1. How are COVID-19 burials different from Ebola burials? (from CDC)

Q&A for 12/7:

#Trends #KY #TN #TX #VA

Question: Following yesterday’s post, how are trends in Kentucky, Tennessee, Texas, and Virginia?

Answer: Also not good. Charts for those four states are below. I made them thanks to data compiled by covidtracking.com.

Figure 1. Kentucky: Daily cases, hospitalizations, and deaths are at their highest ever (7-day rolling average 3,387 cases/day, 1,764 currently hospitalized, 25 deaths/day). Test positivity is quickly rising (averaging 7.1% this last week).

Figure 2. Tennessee: Daily cases, hospitalizations, and deaths are at their highest ever (7-day rolling average of 4,868 cases/day, 2,691 hospitalized, and 56 deaths/day). Test positivity is extremely high at 17% and testing has been very slow to increase. For example, Kentucky averages the same number of weekly tests as Tennessee, but has only 65% the population of Tennessee.

Figure 3. Texas: Daily cases are the highest ever (7-day rolling average 13,150). Hospitalizations and deaths are quickly rising, but have not yet reached the peaks of earlier this summer (7-day rolling average 8,974 hospitalized, 177 deaths/day). Test positivity is extremely high at 14%.

Figure 4. Virginia: Cases and hospitalizations are at their highest ever (7-day rolling average of 2,730 cases/day and 1,829 currently hospitalized). Daily deaths are increasing (7-day rolling average of 20 deaths/day), though they are not yet as high as earlier in the pandemic. Test positivity is increasing (7-day rolling average of 10.5%) and testing has been slow to increase.

Q&A for 12/6:

#Trends #USA #NYS #DC #MD

Question: We haven’t looked at trends for a while. I know things are bad. How bad are they?

Answer: It’s been nearly 2 months since we did a round up of trends. And you’re right. Things are bad and getting worse across the country. I’ll share charts for the US as a whole, New York, DC, and Maryland today. Tomorrow I’ll aim to show charts for states frequently requested — Texas, Kentucky, Tennessee, and Virginia. And if any of you readers want another state, just let me know. All data are from covidtracking.com, which also provides links to local health department data/information in case you want to get more granular.

Figure 1. USA: Cases continue their steep rise with 211K cases yesterday alone. More than 101K are currently hospitalized, and deaths have averaged >2.1K/day over the last week with 2,445 deaths yesterday alone and nearly 15,000 deaths just in the last week. Meanwhile, test positivity is exceptionally high at 10.4%, despite testing continuing to expand (>2.1M tests yesterday alone). Alas, there’s no sign that growth in new daily cases is slowing. The minor decline in new daily cases witnessed last week is likely due to Thanksgiving monitoring and reporting issues, not a true decline in cases. We can expect hospitalizations and deaths to rise as well. But we CAN stop the spread! Masking, distancing, staying home when possible, washing our hands, avoiding closed spaces, crowded places, and close-contact settings.

Figure 2: New York: New cases (10.7K yesterday) are back to the highs of April. Hospitalizations (4.3K currently hospitalized) and deaths (72 deaths yesterday) are also rising, though at a slightly less steep pace than during the initial wave of the spring, which is a small bit of good news. Test positivity (4.8%) was last that high in mid-May.

Figure 3: DC: Cases have exceeded their highs of the first wave (392 new cases yesterday) while hospitalizations (193 currently hospitalized) and deaths (2 deaths yesterday) are also increasing, though like we see in NYS, they are currently increasing at a slower pace than in the first wave. This observation — that hospitalizations and deaths are increasing more slowly in the second wave — is likely due to both a) increased testing finding more mild/moderate cases and b) improved treatment among those hospitalized. Let’s hope that we keep hospitalizations and deaths minimized! And let’s all work together to stop transmission!

Figure 4: Maryland: Cases (nearly 3.2K yesterday alone; ~18K cases in the last week alone) and hospitalizations (156 currently hospitalized) are at their highest levels since the pandemic began. Daily deaths are also quickly rising (30 deaths yesterday; 218 deaths in the last week) as is test positivity (6.5%).

Q&A for 12/5:

#Vaccines #mRNA #DNA

Question: There have been many posts online regarding the vaccines that say the vaccines will change a person’s DNA. That stem cells have been used to develop the vaccines. What should we be concerned about regarding the vaccines, the repercussions?

Answer: There’s a LOT of misinformation about vaccines, especially the new mRNA vaccines like those developed by Pfizer and Moderna. Rest assured, mRNA vaccines do NOT interact with a person’s DNA and are totally UNABLE to affect or change a person’s DNA. We have nothing to worry about on that front. That said, there are real side effects that have been reported with both vaccines, but they have generally been short-lived and none have been serious. Read on to learn more about how mRNA vaccines work and about expected side effects. For the sake of time today, I’m going to punt on your question on stem cells, but if you want to read more check out this article from STATNews and this one from Science.

How do mRNA vaccines work?

This is where a lot of us wish we remember more from our biology classes! Here’s a quick synthesis: DNA is our genetic codebook, located in each cell’s nucleus (deep inner core), which is protected by the nuclear membrane. Ribosomes are located outside the nuclear membrane in the cytoplasm. Ribosomes have the job of making proteins (proteins are the “workhorses” of the cell, doing a whole range of things). But ribosomes can only make proteins based on instructions they receive from messenger RNA (mRNA). Once mRNA shares its instructions, it quickly degrades. Tying this all back to an mRNA vaccine: the shot is administered and it delivers to the local cells mRNA carrying instructions on how to build a piece of the “spike protein” that is unique to SARS-CoV-2. The ribosomes use these instructions to make the spike protein protein piece, which then leaves the cell. As soon as the spike protein piece leaves the cell, the body’s immune system kicks in. Recognizing a protein that does not belong, the immune system produces antibodies and sends T-cells to fight off what it thinks is an infection. This response then allows the body to develop defenses specifically against SARS-CoV-2, making the immune system primed to protect against future infection. An analogy commonly applied is that of a cookbook — DNA is our treasured genetic cookbook that is stored in the library and never removed. If we want to use a recipe from the cookbook, a scribe writes it down on a recipe card (mRNA) that we’re allowed to take to our kitchen (ribosomes) to make the recipe (proteins). After we make the recipe, the card is tossed into the trash where it quickly degrades. The DNA cookbook remains unchanged. To learn more, check out CDC’s Understanding and Explaining mRNA COVID-19 Vaccines. This Q&A on vaccines from Emily Oster is also super informative.

What about side effects?

We don’t have much information to go on here as we’re still working from press releases and related news reports. The FDA will provide a more thorough review of the data in preparation for its emergency use authorization determination, and we should also expect to see peer reviewed studies soon. In the meantime, what we do know is that fatigue and pain are both relatively common reactions to the Moderna and Pfizer vaccines (Table 1). Science had an informative article on this topic a couple of weeks back, Fever, aches from Pfizer, Moderna jabs aren’t dangerous but may be intense for some.

Table 1. Side effects reported among at least 2% of trial participants at dose 1 and/or dose 2, Moderna and Pfizer (from Moderna press release, Pfizer press release)

Q&A for 12/4:

#Self-quarantine

Question: My husband and I own a small business and our only other full-time employee just came down with COVID. We both meet the criteria of “exposed.” How long do we need to self-quarantine?

Answer: I’m sorry. That sounds so stressful. In a bit of slightly good news, CDC just changed the self-quarantine guidelines earlier this week, making them less onerous than the “gold standard” 14 days. For ease of reference, I’ve pasted key portions of the updated guidance herein (Table 1). Basically, to reduce the duration of self-quarantine and as long as you have no symptoms, get tested on Day 5 after exposure; after receiving a negative test result, leave quarantine on Day 7 after exposure.

I’m being more specific here about testing time (within 48 hours of quarantine end) because I want to align with data from CDC’s scientific brief that drove the change in guidelines, Options to Reduce Quarantine for Contacts of Persons with SARS-CoV-2 Infection Using Symptom Monitoring and Diagnostic Testing. As Figure 1 from the brief shows, incorporating PCR testing within 48 hour before self-quarantine ends more than halves the transmission risk at Day 7. Specifically, transmission risk at Day 7 is:

• without testing: 10.7% (range: 10.3–22.1)
• with PCR testing: 4.0% (range: 2.3–8.6)
• with antigen testing: 5.5% (range: 3.1–11.9)

Table 1. CDC’s Updated Self-Quarantine Guidance (from CDC)

Based on local availability of viral testing, for people without symptoms quarantine can end:

• On day 10 without testing
• On day 7 after receiving a negative test result

After stopping quarantine, people should:

• Watch for symptoms until 14 days after exposure.
• If they have symptoms, immediately self-isolate and contact their local public health authority or healthcare provider.
• Wear a mask, stay at least 6 feet from others, wash their hands, avoid crowds, and take other steps to prevent the spread of COVID-19.

Figure 1. Transmission Risk based on length of quarantine and use of testing. (from CDC)

Q&A for 12/3:

#Pulse Oximeter #Oxygenation

Reminder: You can find all posts (from March 9 on) online at https://covidQandA.org

Question: My wife bought a pulse oximeter to monitor for potential COVID symptoms (low oxygen?) and I am skeptical. Is there any evidence that pulse oximeters work for COVID-19 monitoring?

Answer: We do have some evidence that pulse oximeters are useful for monitoring COVID symptoms! Pulse oximeters cannot, however, be used as a COVID diagnostic tool. Low blood oxygenation indicates a health problem, but does not tell you the cause. Meanwhile, regular oxygenation levels do not indicate absence of infection. I’ll describe the evidence in a moment, but let me first describe what a pulse oximeter is/does.

Biology and Pulse Oximeters

Blood is oxygenated in the lungs and is then pumped by the heart to the tissues. Hemoglobin in red blood cells carries oxygen throughout the body. When hemoglobin is carrying oxygen, it is called “saturated.” And blood that is full of saturated hemoglobin is arterial blood (oxygenated blood). Meanwhile, deoxygenated blood is venous blood. Arterial blood is bright red due to its oxygenation whereas venous blood is dark red. In typical arterial blood, 98% of haemoglobin is saturated (SpO2), however when a person doesn’t get enough oxygen (hypoxia), saturation levels are much lower. NIH’s Clinical Treatment Guidelines consider COVID-19 cases to be moderate illness when </=94% of hemoglobin is saturated, and severe illness when <94% of hemoglobin is saturated. To monitor oxygenation levels, the pulse oximeter painlessly goes on a person’s finger and works by shining small beams of red light through the finger tissue — through the blood — to measure the changes of light absorption based on hemoglobin saturation (the light passes differently through arterial and venous blood). For more on this topic, you may find this WHO slidedeck helpful.

Pulse Oximeters and COVID

As mentioned above, pulse oximeters are not a diagnostic tool. That said, they can be very useful for monitoring disease severity and for indicating when you need to seek medical attention. A paper published by the Academy of Emergency Medicine, Novel Use of Home Pulse Oximetry Monitoring in COVID‐19 Patients Discharged From the Emergency Department Identifies Need for Hospitalization, found that “home pulse oximetry monitoring identifies need for hospitalization in initially nonsevere COVID‐19 patients… Half of patients who ended up hospitalized had SpO2 < 92% without worsening symptoms. Home SpO2 monitoring also reduces unnecessary ED revisits.” Another paper published by Applied Clinical Informatics, Remote Patient Monitoring Program for Hospital Discharged COVID-19 Patients, found that remote patient monitoring that includes pulse oximetry “reduces readmissions for patients with COVID-19 and provides scalable remote monitoring capabilities upon hospital discharge.” And finally, an article published in BMJ, What items should be included in an early warning score for remote assessment of suspected COVID-19?, found that pulse oximetry is an important component of an early warning prediction — indicating when a patient needs to seek higher level medical care. All that to say, if you have COVID or COVID-like symptoms and are managing at home (including after hospital discharge) you should use a pulse oximeter to help monitor disease severity (note: pulse oximeters are pretty inexpensive and easy to acquire). And if your oxygenation levels drop, you must seek immediate medical care!

Q&A for 12/2:

#Vaccine #Asthma

Question: When it comes to vaccine distribution, what is the prioritization of underlying conditions? Is asthma included?

Answer: As you’ve probably read, the Advisory Committee on Immunization Practices (ACIP) recommended yesterday that the first groups to get the vaccine be healthcare personnel and long-term care facility residents (Figure 1). We still don’t know the prioritization of underlying conditions, including asthma. A new study was just published last week on the relationship between asthma and COVID infection, COVID-19 Susceptibility in Bronchial Asthma. The results, nicely synthesized in The Jerusalem Post, indicate that people with asthma (both pediatric and adult study participants) could be nearly 30% LESS likely to contract COVID-19, even after accounting for a host of background characteristics (demographic and clinical). The study also found no statistically significant differences in COVID-related hospitalizations by asthma status. Surprising, right?! Turns out, these findings fit with myriad others from various settings including China, Philadelphia, and beyond (check out the discussion section of the paper for more examples). We’re not sure why we’re observing these relationships. A couple of hypotheses were posited by study authors: 1) People with asthma may be more likely to adhere to public health guidance (mask wearing, social distancing, etc.) than the general population; 2) Respiratory allergies are associated with fewer angiotensin-converting enzyme 2 (ACE2) receptors in the lungs, which are known entry points for the SARS-CoV-2 virus to attach and infect host cells.

Figure 1. ACIP Phase 1a Vaccine Prioritized Populations (from slides)

Q&A for 12/1:

#Vaccine #Timeline

Question: I have gotten this question on almost every call I’ve done recently — cancer patients, truck moms, my family— everyone wants to know when they will get their vaccine?

Answer: There’s still a lot that we don’t know yet, which is why there’s no easy answer to this question. Included herein are two things that we can be confident of, followed by a brief discussion of process, and some informed speculation about other priority populations.

Two Things to Be Confident About

1. If you are a healthcare provider, particularly a healthcare provider or support worker caring for COVID patients, you are likely to be among the first to receive the vaccination. Both Pfizer and Moderna require two shots, taken 3 weeks and 4 weeks after the initial shot, respectively. The USA has an estimated 21 million healthcare workers and Pfizer and Moderna estimate that they can have enough product to vaccinate 20 million Americans in December and another 25 million in January. If all goes according to plan, healthcare workers across the country could be fully vaccinated by February.
2. If you are a member of the general population — someone less than 65 years of age, without underlying health conditions, who does not work in an essential job — you will not be in a priority population and can expect to be vaccinated (if all goes according to plan) in June or thereabouts. As reported in the Washington Post, Dr. Fauci stated “I would say starting in April, May, June, July — as we get into the late spring and early summer — that people in the so-called general population, who do not have underlying conditions or other designations that would make them priority, could get” shots.

Process

The exceptionally promising results of the Pfizer, Moderna, and most recently, AstraZeneca vaccine trials mean that we’ll likely soon have initial vaccine distribution! The FDA is reviewing Pfizer’s emergency use authorization request on 12/10 (next week!) and could make a determination within a short few days — perhaps extending to a few weeks. The Federal Government is ready to ship the first 6.4 million doses within 24 hours of FDA approval. As a result of these developments, the Advisory Committee on Immunization Practices is meeting this afternoon(2pm EST!) to finalize priority populations for Phase 1a vaccine distribution and ongoing safety monitoring. The Advisory Committee’s recommendations will go to CDC, and will thereafter likely become CDC guidance. States will use the guidance to inform their vaccine distribution/prioritization strategies, but it is ultimately up to each state to make their own determinations. FDA and Operation Warp Speed have requested that all states submit their final vaccination strategies by this Friday! Draft executive summaries for each state are already online. Between Pfizer and Moderna, an estimated 65 million Americans could be vaccinated by the end of March. For more background, see our Q&A of 11/10.

Other Priority Populations

Within the last day or so, the Washington Post, New York Times, CNN, and STATNews have all run really informative stories about vaccination prioritization. Beyond healthcare workers, people living in nursing homes and assisted living facilities (~3 million people) are likely to be prioritized early on in vaccine distribution. When it comes to other priority populations, an estimated 87 million Americans work in essential jobs — food and agriculture, manufacturing, law enforcement, education, transportation, corrections, emergency response and other sectors. These workers would get priority over the general population, but just what order of priority is still unknown and how essential workers will be prioritized as compared with other priority populations like older Americans (~53 million ages 65+) or Americans with underlying conditions (~100 million) depends on state-by-state decisions. Decisions about people living in other institutions that have witnessed huge caseloads (like prisons) are also forthcoming. Because the vaccine has not been tested in children <12 years of age, they will be among the later vaccination recipients.

While We Wait

It is essential that we continue following good public health practices while we wait for the American population to be vaccinated and even if we are among those Americans to get vaccinated earlier. This means we will need to continue mask wearing, social distancing, etc. well into 2021. Why? Because it takes some time for the protective effect of a vaccine to kick in (perhaps one month or so); Because we still don’t know whether people who are vaccinated can transmit the virus to others; Because the vaccine is not 100% effective. As Dr. Fauci recently stated, “we are not going to turn [the pandemic] on and off, going from where we are to completely normal. It’s going to be a gradual accrual of more normality as the weeks and the months go by, as we get well into 2021.” These vaccines give us some light as we consider the prospects for 2021. In the meantime, we must all do our utmost to stop the virus from spreading further. We can save thousands of lives!

Q&A for 11/30:

#Gym #Risk

Question: We have been letting our daughter (age 11) go to climbing team and dance because the facilities require masks and distancing and have much reduced capacity. I understand that indoor groups with no masks=very bad but I can’t get a sense of the level of risk of indoors with masks and distancing. With numbers going up, we are wondering if we need to cancel these or if a facility taking all the best precautions can still be safe enough. I know nothing is totally safe but I’m looking for some idea of what level of risk we are taking with these so I can balance against her sanity and physical health.

Answer: Your question and dilemma — balancing sanity and physical health with COVID safety — is so similar to the questions/dilemmas facing us all. The odds of contracting COVID depend on four sets of factors (described below and in our Q&A of 11/16). Taking these factors into consideration — with cases on the rise, with infectivity very high in the period before symptoms begin, and with the gym being a higher-risk environment generally meeting the 3Cs — I would consider your daughter’s climbing team and dance activities high risk. At this stage in the pandemic, we need to avoid as much as possible the 3Cs of closed spaces, crowded places, and close-contact settings. To better mitigate risk, keep masks and social distancing, and move the climbing and dance activities outside (buy loads of warm clothes)! When trying to consider risk for other types of activities, try and keep these four factors in mind and try to avoid the 3Cs.

1. Community infection rates: How likely are you to be in the same location with an infected person?

• The pandemic is surging across the country. New cases and hospitalizations are at their highest ever; high test positivity rates are well above the 5% threshold. The likelihood of being among an infected individual increases as community infection rates increase. If you are outside your house in a place with other people, the chances that you interact with an infected person are the highest they’ve been since the pandemic began. Crowded places add to the risk.

2. Person infected: How infectious are they?

• Evidence increasingly shows that people are most infectious “very early in the disease course (a few days before and within the first 5 days after symptom onset).” High infectivity before symptom onset makes the virus especially challenging to contain. Additionally, other factors like heavy breathing — as with exercise or singing — further propel the virus, increasing risk to others. Mask wearing and social distancing help keep the virus from spreading, but they do not offer full protection.

3. Environment: How easily can the virus move through the environment?

• Outdoor environments are much safer than indoor environments. Indoor environments make the virus much easier to spread via airborne transmission, and poor ventilation adds to the risk. Dry air is also associated with increased viral spread (another challenge of winter). And loud environments are associated with increased risk (perhaps because they cause people to shout and expel/inhale more particulates). We do have examples of superspreader events occurring in gym settings, and gym settings generally fit higher risk criteria — 3Cs of closed spaces, crowded places, close-contact settings. (for more, see Q&A of 10/27 and Q&A of 7/10)

4. Person susceptible: How much virus does the person inhale and what is their underlying state of health?

• Young people and people with no underlying health conditions are less likely to experience severe COVID, but evidence increasingly shows that young people are just as likely to become infected as older people and are also just as likely to spread the virus (see Q&A of 11/5). Other factors, like heavy breathing associated with exercise, may increase risk of virus inhalation. And then there are a number of other factors that we just don’t know enough about yet — like enhanced immunity from other coronaviruses or other vaccinations #BCG; or protection afforded by O blood type (see Q&A of 10/15 and Q&A of 9/6).

Q&A for 11/25:

#Mortality #Disparity

Happy Thanksgiving! Q&As will resume on Monday, November 30th.

Question: Yesterday you mentioned that Black American COVID patients are 1.24x more likely to die than White American COVID patients. I thought the rate was much higher than that. This APM Research Lab analysis shows that compared with Whites (and adjusting for age), Blacks have 3x higher mortality. Which is correct?

Answer: To my knowledge, both numbers — terrible as they are — are correct. The APM number is based on the COVID cumulative mortality rate (deaths/100,000 population) whereas the number I cited is based on the August case fatality rate (deaths/cases). Racial disparities in mortality rates are primarily driven by: 1) disparities in who is getting infected; and 2) disparities in who succumbs to the disease. It’s this second piece — disparities in who succumbs to the disease — that the case fatality analysis I described yesterday helps disentangle.

For example, APM’s analysis shows that Asians have the same overall mortality as Whites. Our case fatality analysis, however, shows that Asians have higher case fatality than Whites (1.19x higher in August*). This disparity was masked in the overall mortality rate. Why? Because Asians have been less likely than other racial/ethnic groups to become infected with COVID, but more likely (particularly in older age bands) to succumb to COVID if they become infected. This is a great example of why it’s important to look at case fatality rates alongside mortality rates.**

Finally, since we’re talking about race and health outcomes, I’ll remind us all that race has no genetic basis and is a social construct (see Q&A of 6/7). Stark differences in mortality by race are stark markers of inequalities by race.

*Note: I haven’t re-run the analysis, but to my recollection, the cumulative case fatality rate among Asians is nearly 1.7x higher than the rate among Whites.

**If you ever want to learn more about different mortality frequency measures, CDC’s Principles of Epidemiology in Public Health is a great resource.

Q&A for 11/24:

#Age-adjustment #Disparity

Question: I keep reading news articles like this one that mention “age-adjustment” as related to racial/ethnic differences in COVID hospitalization rates, death rates, etc. I’m not sure that I actually understand what “age-adjustment” is. Would you explain?

Answer: Age-adjustment is a process researchers use to try and make apples-to-apples comparisons between diverse populations. In the United States, the age structure of each racial/ethnic group is quite different (Figure 1). If you want to make comparisons across racial/ethnic groups for outcomes that vary by age — like disease prevalence or mortality — you have to take population composition (age distribution) into account. Enter age-adjustment.

Age-adjustment can be direct or indirect, but for brevity and context I’m going to describe the basic concept of direct age-adjustment (also called direct standardization). Direct standardization is the process of applying age-specific rates (of disease/death/etc.) from our population of interest to a standard population. That may still sound confusing, but believe me, it’s not! Let me further explain using an example from our recent analysis of racial/ethnic disparities in COVID case fatality rates (Figure 2). Reminder: case fatality rates are the proportion of cases that result in death.

On the left side of Figure 2, you’ll see monthly crude case fatality rates by race. On the right side, you’ll see the same rates after age-adjustment. Strikingly different, right?! That’s because the left side — the crude rate — is misleading. Without age-adjustment, the differences between racial/ethnic groups are being driven by population composition, NOT actual disease outcomes. The right side shows the real case fatality differences between racial/ethnic groups. To arrive at the age-standardized rate visualized on the right, we first measured case fatality rates for each 10-year age/race group. We then applied these rates to a standard population — here, all COVID cases in the US. As recently as August, Blacks were still dying of COVID-19 at 1.24x the rate of whites. Age-adjusted case fatality rates reveal dramatically different racial and ethnic disparities that are hidden by crude case fatality rates. Such adjustment is imperative for understanding COVID-19’s toll.

Figure 1. Population pyramids, Hispanics and non-Hispanic Whites, 2013 (from Pew Research Center)

Figure 2. Crude and age-adjusted COVID-19 Case Fatality Rates by Race, March-August (from Fabic, Choi, Bishai)

Q&A for 11/23:

#Masks #Exemptions

Question: I was picking up a few things at the Trader Joe’s and next thing I know, I’m in a fight with another customer who was not wearing a mask… with cases the way they are in Houston! I asked him to put on a mask or leave the store. He said he had bronchitis and was exempt. That can’t be true, right? He’s at a HIGHER risk! Is there any such thing as a mask wearing exemption?

Answer: Dang, that sounds rough! I haven’t had that type of interaction, but I have been reading about “exemptions” and your question prompted me to learn more. Apparently, there are a number of fake “face mask exemption” cards being used, creating widespread skepticism (Figure 1). Despite the deceit, there are actually some real “exemptions” to mask wearing, including “trouble breathing” (further detailed below). Each state’s face mask laws are also varied, further muddying the waters. Texas exemptions include “Any person with a medical condition or disability that prevents wearing a face covering.”

• Per CDC, individuals who have mask wearing concerns due to ongoing respiratory conditions should talk with their health provider about risks/benefits of wearing a mask.
• Key respiratory medicine groups, including the American Lung Association and COPD Foundation, elaborate, “The decision to give this exemption should be at the discretion of the treating physician. However, the individual’s concerns should be weighed against societal needs to mitigate spread of the virus.”
• JAMA published an insightful article on this topic that provides even more detail and nuance, “Mask exemptions during the COVID-19 pandemic — A new frontier for clinicians.” Authors state, “But for many individuals seeking exemption, the risk of participating in public spheres during a pandemic may be high. For those with underlying pulmonary disease, if masking cannot be tolerated, sheltering in place is a reasonable and safe medical recommendation.”
• Finally, a gentle reminder — generally shame is not effective for prompting desired behavior change (see Q&A of 7/2 and Q&A of 9/27).

Excerpts from CDC’s Considerations for Mask Wearing

Masks should not be worn by:

• Children younger than 2 years old
• Anyone who has trouble breathing
• Anyone who is unconscious, incapacitated or otherwise unable to remove the mask without assistance
• Wearing masks may be difficult for some people with sensory, cognitive, or behavioral issues. If they are unable to wear a mask properly or cannot tolerate a mask, they should not wear one, and adaptations and alternatives should be considered.

Most people with underlying medical conditions can and should wear masks.

• If you have respiratory conditions and are concerned about wearing a mask safely, discuss with your healthcare provider the benefits and potential risks of wearing a mask.
• If you have asthma, you can wear a mask. Discuss with your healthcare provider if you have any concerns about wearing a mask.

Figure 1. Fake Face Mask Exemption Card (from NBC)

Q&A for 11/22:

#Illness Duration #Timeline

Reminder: All posts not available at https://covidQandA.org

Question: Is there information about the average duration of the illness? I’m especially curious about illness duration for mild cases who don’t need hospitalization.

Answer: We’ve talked about this a bit in the past (most recently Q&A of 10/5), but it’s worth revisiting, especially since I don’t think I’ve synthesized this information previously. So here goes (see also Table 1 and Figure 1):

Most people will experience mild symptoms or moderate illness.*

• WHO estimates that 85–90 percent of cases are mild to moderate.
• CDC’s current best estimate is that 40 percent of all cases are asymptomatic.

A substantial proportion of cases will be severe.

• WHO estimates that 10–15 percent of cases will become severe; 5 percent become critically ill.

Recovery varies based on disease severity and individual characteristics.

• Asymptomatic people are considered non-contagious and are counted as “recovered” 10 days after their first positive test.
• People with mild/moderate symptoms generally recover in 2 weeks. (WHO)
• People with severe symptoms generally recover in 6 weeks, though it can be longer. (WHO)
• Among symptomatic mild/moderate cases, a substantial proportion (1 in 3) report not returning to full health within 2–3 weeks of symptom onset. (CDC)
• The proportion of “long-haulers” is still unknown, but the numbers are growing (for more, see Q&A of 10/5 or these articles published in JAMA and Nature.

*For a definition of mild/moderate/severe, see NIH treatment guidelines.

Table 1. Disease Severity and Illness Duration

Figure 1. Timeline of illness duration (from WHO)

Q&A for 11/21:

#Reinfection

Question: My daughter is considering attending Thanksgiving at her brother’s home where he and his wife will be entertaining several guests. Apparently, everyone attending except my daughter has already had covid. I am very concerned about her going, especially given that she has Sjogrens. What is the most recent data on reinfection? Can individuals still be able to transmit covid-19 even though they have already had it?

Answer: There’s still a lot about COVID-19 that we don’t know, including how long a person’s immunity to SARS-CoV-2 remains after infection and whether such immunity varies by disease severity or individual background characteristics (like age or sex). We have solid evidence that reinfection can occur (see Q&A of 10/14), however reinfection still seems relatively rare. That said, it’s still difficult to know how rare or common reinfection is because it is really difficult to measure. Science published an article just three days ago, “More people are getting COVID-19 twice, suggesting immunity wanes quickly in some,” which does a nice job synthesizing the current evidence on lasting immunity, reinfection, and ongoing concerns. If a person were reinfected, there’s no reason to believe that they would not be contagious. At this point in our knowledge and experience, no one gets a “pass” to forego mask wearing, social distancing, hand washing, avoiding crowds, etc. — even those who have already recovered from the coronavirus (see CDC guidance on reinfection).

Q&A for 11/20:

#Masks #Reuse

Question: We need to stock up on masks! I like the look and price of this black KN95 mask, but how can I tell if it’s a real KN95 mask? And how many times can KN95 be reused before discarding?

Answer: KN95 masks are made in China and are sold in the US thanks to emergency use authorization (EUA) from FDA. Unlike N95s, they do NOT have FDA clearance or NIOSH approval (reminder N95s are reserved for health workers). This factoid is important for making decisions about whether you’re purchasing a KN95 of acceptable quality (see bullets below). In terms of reuse, CDC offers a set of guidelines, which I’ve synthesized here:

1. Do not reuse if the mask is damaged, ill fitting, or hard to breathe through;
2. Reuse no more than 5 times;
3. Store each mask in its own “breathable paper bag” and wait at least five days before reusing each mask. As CDC states, “This will provide some time for pathogens on it to “die off” during storage.”

Being an informed consumer:

• Is the labeling truthful?: If marketing is misleading, then product quality is questionable and you shouldn’t buy it. For example, if the seller makes claims that it is NIOSH approved, or if there’s NIOSH stamp/logo on the mask or box, don’t buy it. If it claims to be approved for use by children, don’t buy it. And if it claims to be FDA approved or have an FDA logo on the box/marketing materials, don’t buy it. NIOSH shows examples of such incorrect marketing/labeling here.
• Are the prices fair?: Most KN95 masks sell for $2-$3/unit (per CDC). If the masks you’re looking at are going for a rate much higher than that, you’re potentially being subject to price gouging. If you’re paying much less than that, the quality of the product is highly circumspect.
• Is the website suspicious?: Are there typos? Broken links? Does the primary email use a free email service? Is customer feedback a bit off? These can all be red flags indicating that the seller is not legitimate. Steer clear.
• Check the fit: Before buying many masks, consider buying a sample to test the fit. if the mask is loose, don’t use it. Masks with poor ear loop design can be too loose.
• Other factors: CDC offers several other suggestions, but they are generally geared towards a large scale purchaser rather than an individual. For example, NIOSH tests filtration efficiency of different international non-NIOSH approved masks, including many KN95s. Results are available online and can be helpful in making determinations if you know the mask manufacturer. Any mask <95% efficient should NOT be purchased.

Q&A for 11/19:

#Masks #Offices

Question: I have a question regarding wearing a mask at work. Should someone still wear their mask all day even if they have their own office room and are not coming in contact with anyone else during the day?

Answer: The basic guidance is, “Everyone 2 years of age and older should wear a mask in public settings and when they are around people who do not live in their household.” The scenario you described — being alone in your office (assuming 4 walls and a door) — does not fit the criteria of being either a public setting or a place where you’re around other people. You do not need to wear a mask. Read on for more information.

Masking while alone: While CDC has a number of guidelines, including “Employer Information for Office Buildings,” I couldn’t find any CDC guidance that directly answered your question. I did, however, find a number of state/local guidelines and FAQs that directly address this issue. For example, Pennsylvania’s Department of Health states, “Everyone must wear a face covering when indoors, irrespective of physical distance, however, if a person is working alone, and has no expectation of being around other persons, they do not need to do so….”Working alone” means when a person is separated from interaction with other people with little or no expectation of in-person interruption. Examples include:.. A lone worker inside an office with four walls and a door…” The Minnesota Department of Health offers similar guidelines, and so does the Government of San Francisco. This is not a comprehensive list, but I’m sharing these various examples from various places to highlight how common this question is and how similar the guidance is.

One caveat: If you have founded concerns about the adequacy of the ventilation system that your office building is using, you may still want to wear a mask even when you’re alone in your office space. To my knowledge, reopened office buildings are following enhanced ventilation protocols, so this caveat is likely inapplicable to most folks. I raise it because we know that SARS-CoV-2 can be spread via airborne transmission, including from inadequate ventilation or air handling that allows for a build-up of suspended small respiratory droplets and particles. We also know that masks help keep your respiratory droplets from spreading to others and keep others’ droplets from spreading to you.

Q&A for 11/18:

#CFR #Race #Disparity

Question: The new acceleration in COVID cases has me worried. Would you please remind me of the data about those who do not survive it? Average age, pre-existing conditions, etc?

Answer: The acceleration of cases, hospitalizations, and deaths across the country is deeply worrisome. You may feel a wee bit heartened to know that as the pandemic has progressed, patient outcomes have improved. In fact, case fatality rates (e.g. the proportion of deaths among cases) have dramatically declined. Nature had a great article on this trend just last week, “Why do COVID death rates seem to be falling?” Meanwhile, a couple of friends/colleagues, Dr. YJ Choi and Dr. David Bishai, and I dug into CDC’s case surveillance data to understand how national case fatality rates have changed over time by age and race. Just yesterday, we published our results on medRxiv (a preprint server for health sciences). Read on to learn more about our findings. In the meantime, know that case fatality increases with age, racial/ethnic minority status, and underlying conditions. If you’re curious to see the most recent (August) case fatality rates by age and race/ethnicity, check out Figure 2.

Selected Findings from our paper, “Deaths among COVID Cases in the United States: Racial and Ethnic Disparities Persist”

1. CFR has declined over time for all racial, ethnic and age groups (Figure 1);
2. CFR disparities by race and ethnicity are narrowing;
3. CFR disparities by race and ethnicity persist:

• Whites consistently experience lower case fatality.
• Blacks generally experience higher case fatality among younger patients.
• Asians generally experience higher case fatality among older patients.
• High case fatality among Asians has been imperceptible in commonly reported mortality rates.

Figure 1. Monthly age-specific case fatality rates across race/ethnicity groups, March-August

Figure 2. Most recent (August) case fatality rates by race and age

Q&A for 11/17:

#Flying #Airlines #Risk

Question: What have we learned about the safety of flying? Most of the articles I read seem to indicate that flying is just not that big of a risk because of the strong ventilation systems on planes. Is that just airlines trying to get us back to flying or is there independent verification for this science?

Answer: We talked most recently about this issue in our Q&A of 7/1, which includes a cool diagram of airplane ventilation systems. We have more data now, so it’s worth revisiting the discussion. First, let’s remind ourselves of the 3Cs — risk increases with closed spaces, crowded places, and close-contact settings. The degree to which airplanes and airports meet these “high risk” criteria depends on the risk mitigation measures they implement. Flying becomes increasingly safe as airlines/airports implement more public health interventions (often called non-pharmaceutical interventions or NPIs). For airplanes:

• Risk from “closed spaces” is minimized because of the impressive air filtration/ventilation system used on board as well as comprehensive cleaning protocols;
• Risk from “crowded places” can be minimized by reducing passenger capacity. This is a safety/revenue trade off and different airlines have made different calculations. I’ve read that some airlines are moving back to full capacity;
• Risk from “close-contact settings” can be reduced by keeping passengers spaced apart (e.g. not filling the middle seat) and implementing mask mandates for all passengers. Like the crowded places issue, this is a safety/revenue trade off of keeping passengers spaced and the decision/practice varies by airline. Mask mandates are widely implemented, but enforcement seems to vary from airline to airline/aircraft to aircraft.

A recent report from Harvard’s Aviation Public Health Initiative found that when these risk mitigation measures are synergistically implemented, risk of transmission is low. That said, we also have case studies of transmission events occurring on airplanes. For example, earlier this month, CDC’s Emerging Infectious Diseases journal published Transmission of SARS-CoV 2 During Long-Haul Flight. Scientists investigated a cluster of cases among passengers on a 10-hour commercial flight, finding “Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). Seating proximity was strongly associated with increased infection risk (risk ratio 7.3, 95% CI 1.2–46.2).” The upshot is that transmission can absolutely occur on airplanes, but the risk is minimized as more NPIs are implemented and enforced. I suggest that before booking a flight, you research which airlines are implementing the most NPIs. Relying solely on good ventilation is not going to cut it!

Q&A for 11/16:

#Viral Load #Risk #Transmission

Question: A friend of mine told me yesterday that her mom (age 75, but generally healthy) had covid last month (confirmed with 2 trips to the dr, a test and lost sense of taste as well as fever and lethargy, but recovered after 2 weeks with no remaining symptoms), but that her dad, who slept in the same bed with her mom every night and took care of her mom, never got it (he was tested twice). How can someone that close to someone sick not get it?

Answer: Great question that scientists are still trying to answer! Short answer== The odds that your friend’s dad would have contracted COVID are high, but infection is not a certainty.

What are the odds of infection?

As stated above, we don’t fully know the odds, but they are high, especially given the circumstances you describe. Recent findings published in CDC’s MMWR, Transmission of SARS-COV-2 Infections in Households, conclude that “transmission of SARS-CoV-2 among household members was frequent from either children or adults” with the secondary infection rate among household members ages 50+ being 62% (95% CI: 44%-77%). Restated, this study found that 3 in 5 household members ages 50+ contracted COVID from their household member. Now, these data aren’t meant to be extrapolated to the broader population, but I’m sharing them here to reinforce the point that the odds are high. A paper published last month in Physics of Fluid aims to mathematically model infection risk and numerous other scientists are working on similar endeavors.

Why isn’t infection a certainty?

When it comes to COVID, there are many factors influencing transmission (Figure 1). The three main buckets are: 1) amount of virus expelled by the infected host; 2) environmental factors that allow the virus to transport to susceptible host; 3) amount of virus inhaled by susceptible host. But what influences these pathways, especially the infected host factors and susceptible host factors, is still not fully known. When it comes to infected host:

“A growing number of studies estimate that a majority of infected people may not infect a single other person. A recent paper found that in Hong Kong, which had extensive testing and contact tracing, about 19 percent of cases were responsible for 80 percent of transmission, while 69 percent of cases did not infect another person. This finding is not rare: Multiple studies from the beginning have suggested that as few as 10 to 20 percent of infected people may be responsible for as much as 80 to 90 percent of transmission, and that many people barely transmit it.” -Zeynep Tufekci, The Atlantic

As described in a PBS report last month:

“‘It is clear that there are some people who, because of their own personal biology — we don’t know enough about it yet — they produce a higher percentage of aerosols versus respiratory droplets’ [said Dr. Crystal Watson, a public health preparedness expert at the Johns Hopkins Center for Health Security] …. ‘One possibility is that different individuals have respiratory fluid with different viscosity and interfacial tension, both of which affect the dynamics of droplet formation.’ [said Professor William Ristenpart, a chemical engineer at University of California, Davis]”

Figure 1. Factors influencing COVID transmission/infection (from Johns Hopkins)

Q&A for 11/15:

#Isolate #Quarantine

Question: If both my husband and I (we’re the only ones in the house) come down with COVID at the same time, could we care for one another until it’s over and not have to separate?

Answer: At first blush, I don’t see why not, but you know I’m not a doctor and this is they type of question best left to a doctor to answer. Happily, I found relevant guidance from a respected MD, Dr. Eric Toner, an internist and emergency physician, as well as Johns Hopkins Senior Scholar and Senior Scientist. In response to a very similar question he writes,

“They can be isolated together as long as we’re sure they’re both positive. There’s no problem in having multiple people isolate together. But, ideally, people should quarantine separately. It’s also important to distinguish between isolation and quarantine: isolation is for people who are sick. Quarantine separates and restricts the movement of people who may have been exposed to the virus.”

So there you have it. If you are both positive with the virus, you can both isolate together.

Q&A for 11/14:

#China #Four Earlies

Question: I heard an expert mention China’s “four earlies” strategy as a key approach for effective pandemic response/containment. What are the “four earlies”?

Answer: In response to the SARS outbreaks of 2003–04, China implemented the “4 earlies” strategy, which is about quick, timely response to curb viral spread and improve patient outcomes. The “four earlies” strategy, hailed by Dr. Zhong (China’s equivalent to America’s Dr. Fauci), continues to be a lynchpin of China’s response to COVID-19. The “four earlies” are —

1. Early identification

• In practice, this is widespread testing with rapid results. Just last month, China tested an entire city of 4.7 million people to curb a regional outbreak. Thanks to massive testing capacity, results are generally returned in a matter of hours (though for such massive testing campaigns, the return time has been longer 2–4 days). China has also used widespread temperature checks, though I’m not sure if this strategy is still used as evidence of its effectiveness is lackluster. Just yesterday, research published in CDC’s MMWR concluded “Symptom-based screening programs are ineffective because of the nonspecific clinical presentation of COVID-19 and asymptomatic cases.”

1. Early reporting

• This component is largely about contact tracing. In China, it includes interoperable systems and a huge digital infrastructure with loads of privacy concerns. (Figure 1)

1. Early isolation

• Recognizing that isolation at home can put other household members at risk and that COVID symptoms can quickly progress from mild/moderate to severe, China set up isolation centers (Fangcang hospitals) — hospitals established within public venues such as stadiums and exhibition centres — where mild/moderate cases would isolate and be quickly transferred to medical services if symptoms became severe.

1. Early management

• With regard to patient outcomes, the Report of the WHO-China Joint Mission summarizes, “early identification of cases and contacts allows for earlier treatment.” Connecting cases with care has been a key element of China’s approach, including (during the height of the epidemic) by having mild/moderate cases isolate in Fangcang hospitals to be monitored and treated and moving them to more intensive care as soon as needed.

Figure 1. China’s digital health system (from Mercator Institute for China Studies (MERICS))

Q&A for 11/13:

#Dentist

Question: I am overdue for dental cleaning. Over a year since I cancelled last fall with my shattered ankle. I have concerns about our #1 hygienist who had Covid in June, recovered, but now wears her mask UNTIED … hanging from her ears. No shield. Should I pick another more buttoned up hygienist in the office?

Answer: We talked about dentists and risk way back in our Q&A of July 11. Since then, CDC’s guidance for dental settings has been updated, and now includes the recommendations regarding eye protection in addition to mask protection (copied below). Because your hygienist is not following hygienic practices, I recommend finding another one. I also wonder why the dental practice allowed the hygienist to flout the rules. What’s going on with the practice overall?

A few more thoughts:

• We don’t know how lasting immunity is from coronavirus infection. This gap in knowledge means that we do not have certainty about whether/under what circumstances a person who has contracted COVID-19 once can get it again. We now know that it is possible, with a few documented case studies of true reinfection (see Q&A of 10/14). Note: possible and probable are obviously not one in the same.
• Because masking has not been a fully adopted social/behavioral norm, it is important for community leaders, health care providers, family members, friends, and more to model the behavior as an important avenue towards changing social norms. (if you’re interested, brief descriptions of social behavior change theories are here)
• Masks are protective not just against COVID, but against other viruses transmitted through respiratory drops and air. Even if your hygienist were immune to COVID, she’s not immune to a host of other viral pathogens.

Excerpts from CDC’s Guidance for Dental Settings

Dental healthcare personnel should wear a face mask or cloth face covering at all times while they are in the dental setting, including in breakrooms or other spaces where they might encounter co-workers.” [emphasis CDC’s]

In areas with moderate to substantial community transmission, during patient encounters with patients not suspected of SARS-CoV-2 infection, CDC recommends that dental healthcare personnel (DHCP):

• Wear eye protection in addition to their facemask to ensure the eyes, nose, and mouth are all protected from exposure to respiratory secretions during patient care encounters, including those where splashes and sprays are not anticipated.
• Use an N95 respirator or a respirator that offers an equivalent or higher level of protection during aerosol generating procedures.

Q&A for 11/12:

#Nasal Irrigation #Treatment

Question: Given that the virus is transmitted through the respiratory system, should we be doing nasal irrigation (Neti Pot) more often?

Answer: Interesting question! So far (considering limited direct evidence), data indicate that yes, nasal irrigation is beneficial, especially to reduce COVID symptom duration. Nasal irrigation has been shown to reduce symptoms and have therapeutic effects for all sorts of ailments. The practice stems from India, where it has been recommended by Yogic texts and used for centuries. I was curious to read a few studies and research notes specifically about nasal irrigation and coronavirus. And here’s a brief synthesis of what I found:

• Nasal irrigation can reduce symptom duration and transmission within household contacts of the common cold. This paper published last year in Nature, “A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold,” published results of a small randomized control trial comparing hypertonic saline nasal irrigation and gargling vs standard care on healthy adults within 48 hours of upper respiratory tract infection. Researchers found “duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log10/day (p = 0.04).”
• Nasal irrigation likely decreases viral burden through physical removal of viral particles. This viewpoint published by JAMA Otolaryngology in July, “Benefits and Safety of Nasal Saline Irrigations in a Pandemic — Washing COVID-19 Away” suggests that nasal irrigation is likely to reduce viral load and recommends, “Given the safety profile of these therapies, HS nasal irrigations should be encouraged for patients and health care workers especially.”
• Nasal irrigation seems to reduce symptom duration in COVID-19 patients. This interim analysis of a randomized control trial undertaken at Vanderbilt University, published in the International Forum of Allergy & Rhinology found “The effect of nasal irrigation on symptom resolution was substantial, with nasal congestion and headache resolving a median of 7 to 9 days earlier in the intervention groups.”

Two caveats: 1) Nasal irrigation materials and their surrounding area could potentially become contaminated and serve as a source of future infection; 2) FDA considers nasal irrigation systems safe, but also warns that use of tap water for nasal irrigation and/or improper cleaning nasal irrigation devices can results in serious infection. Please practice good hygiene! CDC provides guidance for safe use of nasal irrigation devices here.

Image 1. Nasal irrigation in practice (from FDA)

Q&A for 11/11:

#Masks

Happy Veterans Day!

Question: What’s the new masking guidance?

Answer: Yesterday CDC updated it’s masking scientific brief, stating unequivocally that not only does wearing a mask protect others, it also protects you!

“Masks are primarily intended to reduce the emission of virus-laden droplets (“source control”), which is especially relevant for asymptomatic or presymptomatic infected wearers who feel well and may be unaware of their infectiousness to others, and who are estimated to account for more than 50% of transmissions.1,2 Masks also help reduce inhalation of these droplets by the wearer (“filtration for personal protection”). The community benefit of masking for SARS-CoV-2 control is due to the combination of these effects; individual prevention benefit increases with increasing numbers of people using masks consistently and correctly.”

We talked about protection that masks afford the wearer back in our Q&A of 8/25 and now there’s enough accumulated evidence to say, YES, masks also protect the wearer! And as CDC further states,” Adopting universal masking policies can help avert future lockdowns, especially if combined with other non-pharmaceutical interventions such as social distancing, hand hygiene, and adequate ventilation.” Please share this news widely and continue to encourage all of your friends, family, and social network members to wear their mask!

Q&A for 11/10:

#Vaccination #Prioritized Populations #Children

Note: After some nudging from several of you avid readers, I made a website — www.covidQandA.org-- so that these daily questions and answers are easier to find. Please use and share the resource with others! Share suggestions with me! And keep sending questions and expecting daily emails.

Question: It’s likely Pfizer gets the Emergency Use permission, but what does that mean for your average American? Who would get the vaccine under the Emergency Use designation? And what about vaccines for children?

Answer: From what I’m reading, including this helpful overview from the NY Times, if everything goes as well as possible (that’s a big if), the vaccine could be authorized for use among certain high risk populations by the end of the year. Pfizer and its partner, BioNtech, expect to have 30–40 million doses available by the end of the year, and to further ramp up to 1.3 billion doses/year (note: as described in Nature, full vaccination= 2 doses with 2nd dose given 3 weeks after 1st). Clearly, it will take some time for the whole population to be vaccinated.

Which populations are prioritized for initial vaccine distribution?

A few days ago (11/5), CDC issued the COVID-19 Vaccination Program Operational Guidance to help each state, local, territorial, and Tribal government “plan and operationalize a vaccination response.” Included in the Guidance is each state’s draft executive summary, which describes (among other things) the populations that will be prioritized in the initial vaccine distribution. For New York, “prioritization of population groups will be based on risk, maintenance of essential services, and community prevalence of COVID-19…. more than 800,000 critical health care workers in hospitals, long term care facilities (LTCFs), emergency medical services, and home care and approximately 83,000 LTCF residents will be targeted during the initial phase of limited vaccine supply. As more vaccine becomes available, other frontline essential workers, medically high risk individuals, and individuals over 65 will be targeted.” You can check out your state’s draft plan executive summary here.

What about children?

Pfizer trial participants originally included those ages 18+, who are not pregnant, in good general health and have not been previously diagnosed with COVID-19. In October, Pfizer received FDA approval to expand enrollment to include those ages 12–17. You can read more about the trial’s plans from clinicaltrials.gov, here. Generally, trials start with healthy adults and as safety is proven, they work their way to younger and younger populations, from teenagers down to young children. This process allows vaccine developers to adjust dose to minimize side effects and maximize immune response. While the inclusion of children ages 12–17 is fantastic news, data on vaccine safety and effectiveness for younger children is still missing. A vaccine for younger children will still be some time in coming — some experts estimate Fall 2021. Meanwhile, because pregnant and breastfeeding women have been excluded from this trial (and the preponderance of others), we will have to rely on the safety/efficacy evidence stemming from those who become pregnant while enrolled in the trial(s). A good run-down of the issues of vaccines and pregnancy is offered by Johns Hopkins experts, “Will Coronavirus Vaccines Be Safe for Pregnant Women?”

How were priority populations determined?

CDC is making COVID-19 vaccination recommendations based on input from the Advisory Committee on Immunization Practices (ACIP), a federal advisory committee of medical and public health experts. In the context of limited vaccine supply, ACIP offers these four goals for prioritizing distribution:

• Decrease death and serious disease as much as possible
• Preserve functioning of society
• Reduce the extra burden the disease is having on people already facing disparities
• Increase the chance for everyone to enjoy health and well-being

Based on these four goals, ACIP suggests that four groups be initially prioritized: Healthcare personnel; Workers in essential and critical industries; People at high risk for severe COVID-19 illness due to underlying medical conditions; and People 65 years and older.

Finally, several other groups have issued vaccine prioritization recommendations, which informed ACIP’s recommendations, including:

• Johns Hopkins Bloomberg School of Public Health: Interim Framework for COVID-19 Vaccine Allocation and Distribution in the United State
• The National Academies of Sciences, Engineering, and Medicine: Framework for Equitable Allocation of COVID-19 Vaccine
• WHO Strategic Advisory Group of Experts (SAGE): WHO SAGE Values Framework for the Allocation and Prioritization of COVID-19 Vaccination
• WHO SAGE: WHO SAGE Roadmap for Prioritizing Uses of COVID-19 Vaccines in the Context of Limited Supply

Q&A for 11/9:

#Vaccination #Immunity

Question: What’s the run-down on today’s Pfizer vaccine news?

Answer: Pfizer’s vaccine news of this morning — early trial results show the vaccine to be 90% effective in preventing disease among trial volunteers with no concerning side effects — is very exciting! 90% is MUCH higher than most scientists have been expecting. If it continues to prove this effective, it will be a vaccine more like childhood immunizations (e.g. MMR) than influenza vaccinations!

The New York Times had a very informative article on the news this morning, here. Basically, the Data Safety Monitoring Board met this weekend to assess the trial’s progress based on data from the first set of volunteers to contract COVID-19. As it turns out, ~90% of the 94 volunteers who contracted COVID-19 were those who were in the placebo group! This is something to smile about. BUT, the data are preliminary and things can still change. All we have right now is the press release; no peer reviewed findings yet! Furthermore, we still have several additional questions that the ongoing trial will resolve:

• Can vaccinated people be asymptomatically infected and thus able to spread the virus to others (e.g. be carriers)?;
• Does the vaccine impact disease severity?;
• What is the duration of protection?

Background

This vaccine (administered in 2 doses/shots) is a new type of vaccine based on RNA technology. As described by the NY Times, “It takes genetic material called messenger RNA and injects it into muscle cells, which treat it like instructions for building a protein — a protein found on the surface of the coronavirus. The proteins then stimulate the immune system and are believed to result in long-lasting protection against the virus. Other companies, including Moderna, are also using messenger RNA technology.” The new vaccine did not receive any development funding from Operation Warp Speed, however, the US placed a purchase order in July for 100 million doses. Company executives expect to have manufactured enough doses to immunize 15 to 20 million people by the end of the year.

Timing

The Phase 3 trial is expected to continue until 164 people in the 44,000 person trial have developed Covid-19. Since COVID is so rampant, achieving this milestone should not be long in As STATNews reported today, “In keeping with guidance from the Food and Drug Administration, the companies will not file for an emergency use authorization to distribute the vaccine until they reach another milestone: when half of the patients in their study have been observed for any safety issues for at least two months following their second dose. Pfizer expects to cross that threshold in the third week of November.” For more on vaccine development, see NY Times Coronavirus Vaccine Tracker (Figure 1).

Figure 1. Vaccine Tracker (from NY Times)

Q&A for 11/8:

#Exposure #Self-quarantine

Question: My son had a contact with a boy (band mate, practicing in an open garage for about 20min on Thursday) who got a positive test the day after. We are currently keeping my son isolated. Four questions: 1) Should he get tested or should he just be quarantined for two weeks? 2) If we can reduce the length of quarantine based on a test result, when is the optimal time for my son to be tested?; 3) There was about a 48 hour window between my son’s contact with the boy and the self-quarantine (Thursday and Saturday). We, the rest of the family, wonder if he might have become contagious and thus we were also exposed and need to be quarantined. Should we? 4) If so, when is the optimal time for us to get tested? We are self-quarantined for now. Ugh…

Answer: I’m sorry, that all sounds quite stressful. First off, it’s important to assess whether your son meets the criteria of “close contact” — any individual within 6 feet of an infected person for a total of 15 minutes or more. Based on your description, it sounds like the answer is yes. In which case, you’re doing the right thing by having him self-quarantine. Now let’s turn to your specific questions:

1. Should he get tested?:

• Yes, your son should get tested. CDC recommends testing for all “close contacts” of confirmed positive individuals. (Figure 1)

2. Can we reduce the length of quarantine based on a negative test result?:

• No, you cannot reduce the duration of self-quarantine based on a negative test result. Because the COVID-19 incubation period ranges from 2–14 days (median 5 days), a negative test result before the end of the 14-day quarantine period does not rule out possible infection.

3. Should we consider ourselves exposed?:

• There’s not a straightforward answer. We know that people are very contagious 24–48 hours before they develop symptoms. And we know that it takes some time after exposure for a person to begin shedding the virus themselves. What we don’t know is how long that window is between exposure and viral shedding is, especially because it seems to vary from person to person. If most symptoms begin around day 5 and people are highly contagious 48 hours beforehand, we can surmise that individuals may become very contagious at day 3. Since it also takes time for the virus to replicate and viral shedding to begin, we can surmise that the risk of being contagious at day 1 is exceedingly low. Day 2 of exposure is murkier. However, you and your family were not necessarily directly exposed! Rather, you were with your son, who was exposed, but not necessarily infected. This is another reason why it’s so important for your son to get tested. If his test comes back positive, you know to consider yourselves exposed and to self-quarantine. If his test comes back negative, it’s again murky. It’s possible to get a negative result and still be contagious. As Johns Hopkins professor, Dr. Justin Lessler, told CNN earlier this week, “The virus just takes time to replicate in the body to detectable levels. You can get infected by just a few viral particles, but these will not be detectable until they have time to replicate to adequate levels to be detected.” If you and your family can do it, it’s probably the most prudent to self-quarantine.

4. When is the optimal time to get tested?:

• Testing seems to be most accurate when done at either a) symptom onset OR b) 4–5 days after exposure (see Q&A of 10/22 #Testing)

If you want more information, the Virginia Department of Health’s website on COVID exposure and MIT page on COVID exposure and are both informative and easy to read.

Figure 1. Summary of Recommendations for Close Contacts (from CDC)

Q&A for 11/7:

#Test Types #Rapid Molecular Tests

Question: What is a rapid molecular test? I was tested recently (with results in about 20 minutes), and the provider said it’s not PCR but more accurate than the antigen RDT. Is it worth finding/going to places where they offer rapid molecular tests, as opposed to antigen tests?

Answer: The Infectious Disease Society’s COVID-19 Real-Time Learning Network offers a great overview of rapid testing, which describes the differences between rapid molecular testing, antigen testing, and standard PCR testing. I took their synthesis and made a chart (Table 1) to show the similarities and differences. When it comes to which test to use, the Infectious Disease Society’s guidelines, “make no recommendations for or against using rapid tests (i.e., result time ≤ 1 hour) versus standard RNA testing in symptomatic individuals suspected of having COVID-19, citing knowledge gaps.”

As far as I can tell, when it comes to finding/going to places with specific test types, I think it depends on what you care most about — speed, accuracy, convenience, etc. Among the test types and based on what we currently know, rapid molecular tests seem to offer the best balance of speed, accuracy, and perhaps even comfort (re: sample collection). If it were me, that would likely be the test I’d aim to get. That said, it’s also really challenging to figure out what test is being offered by what provider. I might just go where the provider can see me the soonest (especially if I’m feeling unwell) or where I can be tested from my car (especially if I want to avoid sitting in a waiting room). What I’m saying is that a constellation of factors is at play for each individual going to get a test; ultimately, any of the three test types will get you the information you and your doctor need.

Related note: even though antigen tests fare less well at detecting true positives (moderate sensitivity), symptomatic individuals who test negative on the antigen test will then be given a PCR confirmatory test, per testing guidelines.

Table 1. Differences between Standard RNA/PCR tests, Rapid molecular tests, and rapid antigen tests.

Q&A for 11/6:

#False Positive

Question: In a place like DC where the positivity rate has hovered in the 1–3% range, what percentage of the positive tests reported are actually probably false positives? Is there any accounting for that in the reporting? And if I were to get a positive test result without having direct exposure (like I tested after flying just to be sure), what are the odds that the test result is a true positive?

Answer: Good questions! On the false positivity front, the answer depends on a few variables:

1. Test you’re using — PCR have higher sensitivity and specificity (they are more precise) as compared with antigen tests. (see Q&A of 9/4 #Test Types)
2. True incidence within the population being tested — the higher the incidence within the population tested, the lower the false positivity rate. (see Q&A of 4/15 #Sensitivity)
3. Timing of when you get tested — No test is able to detect the virus if you get tested very soon after exposure. Antigen tests are less likely to detect the infection if you are tested too late in the course of the disease. And PCR tests can detect the virus long after your body has cleared it. (see Q&A of 10/24 #Antigen)
4. Your health history — If you have symptoms or have recently had known exposure to someone infected with COVID, the possibility of false positive is minimized.
5. Specimen quality and lab quality — Did the health provider correctly conduct the nasal/throat swab? Did the laboratory follow all quality controls?

When it comes to DC, it looks like molecular PCR tests are still the main tests being used. The Foundation for New Innovative Diagnostics has been independently evaluating the sensitivity/specificity of COVID-19 molecular (PCR) tests and modelers who recently published in Lancet Infectious Diseases pooled these results to estimate that molecular tests have a sensitivity at symptom onset of 90% (range: 80%-95%) and specificity of 100%. 100% specificity seems overly optimistic, so I’m going to go with 99%, which is well within the 95% confidence interval. Reminder: sensitivity is the ability of the test to identify all people who are actually infected; specificity is the ability of the test to identify all the people who are actually not infected. Table 1 shows how the false positive rate changes based on different levels of incidence; if we estimate that true incidence among people getting tested in DC is 3%, then we’d expect 27% of positive results to be false positive. However, I’d like to remind you that these sensitivity/specificity estimates are based on testing at symptom onset. Because lots of folks are *not* getting tested at symptom onset, because a substantial proportion of cases remain asymptomatic, and because of the many other variables listed above, it’s really hard to estimate the proportion of cases in DC that are actually false positive. And as I said before, you’re very likely to get a negative test if you test too early in the course of infection.

On the aggregate, as incidence increases (see 7% and 10% scenarios below), the number of false positives and false negatives begin to balance each other out, and as incidence increases beyond 10%, the number of false negatives outweighs the number of false positives. To my knowledge, no state accounts for false negatives/positives in their reporting. In my opinion, that’s for the best, since there are so many assumptions required for making false positive/negative estimates.

Table 1. PCR Testing False Positive Rates under different Incidence Assumptions.

Q&A for 11/5:

#Schools #Reopening #Mitigation

Question: Any thoughts of correlation of record high national cases and schools being open? I see a lot of schools are not spreading the virus stories but also that kids can be asymptomatic spreaders. It is confusing.

Answer: When reopened with appropriate risk mitigation measures, schools (K-12) seem to be low-risk transmission environments (see Q&A of 10/13 #Reopening and recent research from Spain here). But we still don’t have a good picture of schools and risk because we’ve done a terrible job collecting, analyzing, and sharing comprehensive data on schools. In fact, my friend and public health expert, Dr. Nirali Chakraborty, wrote a commentary on this very issue published yesterday in the Baltimore Sun, “Private schools could teach public systems about COVID — if they’re willing.” To further elaborate, let me start with three pieces of information that were unknown earlier in the pandemic:

1. Children can contract and spread the virus (some relevant research is here and here, more background is in our Q&A for 9/2 #Kids);
2. High-risk transmission settings are those that include closed spaces, crowded places, and/or close-contact settings (see Q&A for 10/30 #3 Cs); and
3. Most of the SARS-CoV-2 transmission occurs in the home among family units, however, these individuals are less likely to infect others outside of their homes. The bigger spread comes from bursts where one person infects many (e.g. super-spreader events) (see Q&A for 10/9 #Overdispersion, and some relevant research published in Nature here and here).

Taking this information into account, we can surmise that schools as we knew them pre-pandemic — closed spaces, crowded places, close-contact settings — meet all the criteria of being potential high-risk transmission sites (e.g. super-spreader sites). So when we’re talking about school reopening, we have to put it into context. Are we talking about reopening schools as they were pre-pandemic? If so, the transmission risk is high, particularly in areas with moderate to high levels of community transmission. But to my knowledge, that’s not what we’re talking about. We’re talking about school reopening in the context of risk mitigation measures. Then the question becomes — in the context of limited resources, which risk mitigation measures are the most effective?

And this is where we need better data across the country from public and private schools — on mitigation measures implemented, protocols adopted, case counts, school-based transmission, and more. Individuals are trying to fill the gap, but their data are limited and include only those schools that opt-in (Q&A of 10/13 #Reopening). We need our local, state, and federal governments to help us make informed decisions! As Dr. Chakraborty wrote in her commentary about Maryland (but it’s applicable to any state, in my opinion),

“… the state of Maryland should be leading the way for governmental data reporting standards, building the trust that is so needed among parents, teachers and school systems so that our children can be back in school, where they belong. Many parents are being asked to make the decision of whether to send their children back to a hybrid model, or remain virtual… parents, striving in an information void, to make the best decisions they can. Fill the void, and more children may return to school.”

Finally, a recent working paper (not yet peer reviewed) written by scientists at Spain’s Universitat Politècnica de Catalunya explored whether community infection rates were correlated with school reopening in Spain, concluding that school reopenings were not associated with increased incidence of community transmission. As described in a related NPR report, schools in Spain reopened with numerous safety measures, including “mask-wearing for all children older than 6, ventilation, keeping students in small groups or “bubbles,” and social distancing of 1.5 meters — slightly less than the recommended 6 feet in the United States. When a case is detected, the entire “bubble” is sent home for quarantine.” These findings add to the growing evidence-base that when reopened with appropriate risk mitigation measures, schools (K-12) seem to be low-risk transmission environments.

To conclude, I think that we’re generally talking about schools and risk incorrectly. I see so many questions like, “Are schools safe?,” when we need to be asking, “Which mitigation measures should we mandate for schools to safely reopen, especially in the context of limited resources?; Of the schools that have reopened successfully, what have they done?” Comprehensive, publicly available data are required to answer these key questions and ultimately get our children and teachers safely back into school buildings!

Q&A for 11/4:

#Sex

Question: Are there guidelines for safe sex with a new partner who you don’t know very well yet?

Answer: We discussed safe sex in our Q&A of 6/6 #Sex, where I shared a table regarding safe sex practices that is still highly relevant. I thought there might be more evidence to report here, but there’s not much; the role of sexual transmission (e.g. through semen, vaginal fluids, oral-fecal routes, and/or saliva) is still uncertain. Among COVID-19 patients, SARS-CoV-2 has been detected in saliva, semen, urine, and fecal matter, but it has *not* been found in vaginal fluids (though this study linked here is very small). Even though the virus has been detected in bodily fluids, whether the virus has spread through these routes is still unknown.

Since the virus is predominantly spread through respiratory droplets shared in close contact, since sexual intercourse with a partner requires close contact, and since the virus can spread before a person knows they are sick, SARS-CoV-2 transmission risk during sexual intercourse with a partner who has been exposed or whose exposure is unknown is high. If sexual partners decide that the risk is worth it, they can minimize the SARS-CoV-2 transmission risk by using condoms and dental dams, avoiding kissing, opting for sexual positions that are not face-to-face, wearing face masks, and washing hands/showering before and after getting intimate. If they want to really minimize transmission risk, they can also agree to self-quarantine for 14 days and get together thereafter, as suggested by University of Maryland Medical System.

Q&A for 11/3:

#Fomite Transmission #Groceries

Please vote!

Question: At the outset of COVID, we were advised to wipe down surfaces, including such things as grocery deliveries and mail. I even took to wiping down my keys, phone, and wallet after returning from a trip outside, before washing my hands. Does current advice regard this as obsessive, phobic, and superfluous, as my brother suggests, or is it still the right approach, if ever it was?

Answer: We have evidence that the virus can live on surfaces based studies conducted in laboratory settings. More recent studies in “real world” settings have confirmed that viral particles can be found on high touch surfaces, however, no viable virus has been detected (e.g. the virus detected is unable to infect others) (Table 1). This overview published in Annals of Internal Medicine in September, “Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors,” provides an informative description of what we know and don’t know about fomite transmission. The authors conclude, “On the basis of currently available data, we suspect that the levels of viral RNA or live virus transiently remaining on surfaces are unlikely to cause infection, especially outside of settings with known active cases.” The upshot is that the risk of fomite transmission is theoretical and the risk very low. In settings where there are no known cases, the risk is exceedingly low. As described in our Q&A of 10/30 #3 Cs, the most important way to stop fomite transmission is to wash your hands frequently and avoid touching your face.

As Dr. Fauci stated last week, “We also know that the virus can live on inanimate objects…that is very likely a very, very minor, minor aspect [of transmissibility]. We can’t say it’s zero. It certainly is real and is finite, but it’s minor…. I think we should spend less time worrying about wiping down a grocery bag than we should about just washing our hands frequently… So you asked me what I do when I come from the grocery store or when someone gives me a take-out bag, which I do a lot now, because I don’t go into restaurants and sit down. I want to keep them going financially. So I do a lot of takeout. So I do have a bag that I bring into my house. Instead of worrying about the bag, I’ll open the bag and then I’ll just wash my hands thoroughly, which is what you should do.”

Table 1. Review of Studies Assessing Viral RNA in Real World Settings (from Annals of Internal Medicine)

Q&A for 11/2:

#Excess Deaths #Dimensia #Car Accidents #Violence #Overdoses

Question: This NY Times article, “Nursing Homes, Racked by the Virus, Face a New Crisis: Isolation,” made me wonder how many of our seniors are dying early and alone in nursing homes due to lockdowns meant to protect them. Is anyone keeping track of excess deaths from domestic violence, drug overdoses, suicides, or loneliness over the last 8 months?

Answer: CDC’s National Center for Health Statistics (NCHS) keeps track of national-level data for a slew of things, including deaths and excess deaths (for more on NCHS, see Q&A of 7/31 #Mortality and Q&A of 5/5 #Coding Deaths). We can find data on excess deaths in the United States related to COVID online, synthesized here. Figure 1 shows the number of excess deaths by underlying cause for those comorbid conditions that are frequently reported alongside COVID. As you can see, deaths due to Alzheimers and other forms of dementia represent the largest number of excess deaths (33,020 excess deaths as of 10/10, incomplete reporting). Unfortunately, there’s still a lot we don’t know. First, as described in a recent CDC MMWR report on this topic, “…deaths from circulatory diseases, Alzheimer disease and dementia, and respiratory diseases have increased in 2020 relative to past years, and it is unclear to what extent these represent misclassified COVID-19 deaths or deaths indirectly related to the pandemic.” Second, because deaths due to injury (e.g. accidents, homicides, suicides) have especially lagged reporting times, NCHS excluded them from this initial cause of death reporting. Clearly, much more data and research are required to really answer your question. In the meantime, several other researchers have attempted to look into this question and here’s a snippet of what they’ve found:

• Deaths due to motor vehicle accidents decreased during March and April, but have since rebounded and even surpassed recent June/July/August trends (based on preliminary data shared by the National Safety Council’s Injury Facts and visualized by me, Figure 2)
• COVID shutdowns were associated with a decrease in overall crime, as described in this paper published in July in the American Journal of Criminal Justice, “Has COVID-19 Changed Crime? Crime Rates in the United States during the Pandemic”. However, overall crime drops hide changes by crime type. Study authors state, “Compared to the pre-pandemic year of 2019, crime — as measured by calls for service to law enforcement — has decreased markedly. However, there are multiple indications that the crime drop is being driven by decreases in minor offenses which are typically committed in peer groups. At the same time, serious crimes which are generally not committed with co-offenders (namely homicide and intimate partner violence) have either remained constant or increased. As such, the crime drop appears to be hiding a very disturbing trend where homicides remain unchanged and intimate partner batteries are increasing.” Once the FBI’s National Incident-Based Reporting System has 2020 data, we can explore violent crime trends even further.
• Domestic violence has increased alongside lockdowns, as hypothesized in this perspective published in New England Journal of Medicine and revealed in multiple studies, including: this study from Massachusetts published in Radiology, which concluded, “There was a higher incidence and severity of physical intimate partner violence (IPV) during the COVID 19 pandemic compared with the prior three years.”; and this overview from the Journal of Clinical Nursing, which described (among other things) that, “In the UK, Refuge, one of the leading domestic abuse organisations reported that calls to the UK Domestic Violence Helpline increased by 25% in the seven days following the announcement of tighter social distancing and lockdown measures by the government. During the same period, there was a 150% increase in visits to the Refuge website.”
• Overdoses are also increasing. As the American Medical Association stated in its October issue brief, “ the nation’s opioid epidemic has grown into a much more complicated and deadly drug overdose epidemic. The AMA is greatly concerned by an increasing number of reports from national, state and local media suggesting
  increases in opioid- and other drug-related mortality — particularly from illicitly manufactured fentanyl and fentanyl analogs.” Overdoses have been increasing over the last several years, so the degree to which this worrying trend is associated with COVID is still unknown.

Figure 1. Number of Excess Deaths by Cause (from NCHS)

Note from NCHS: “…weekly counts of deaths due to select causes of death are presented. These causes were selected based on analyses of comorbid conditions reported on death certificates where COVID-19 was listed as a cause of death.”

Figure 2. Motor-Vehicle Fatalities (data from National Safety Council Injury Facts)

Q&A for 11/1:

#Self-quarantine #Time

Question: The organization I work for provides in-home services for children and teens with severe mental health issues. After suspending in-person services for 6 months, we are now returning to homes with a lot of safety precautions in place. One question that has come up — what is the best course to follow if the family has had known exposure to Covid (one of our screening questions prior to each visit)? On the one hand, we know testing is not always accurate; a family can get tested following exposure and be negative whereas a few days later they might actually show as positive. On the other hand, we can stay out of the home for 10 days as we allow the family to monitor for symptoms, however after 10 days they could be asymptomatic while still being Covid-positive and contagious. What is the best way to provide services to families with as little disruption as possible while also keeping our employees safe?

Answer: This question reminds me of the Q&A from 7/4 #Assymptomatic Transmission. You are right that the risk of false negative results, particularly early on in the infection, is real. This is why testing alone is insufficient; testing + self-quarantine is the best approach. As far as I understand it, the best course to follow if a family has had known exposure is to:

1. Find out when that last known exposure transpired;
2. Ask that the family member(s) who had the exposure get tested, ideally 4–5 days after exposure or as soon as symptoms appear (see Q&A of 10/22 #Testing);
3. Assuming that the test is negative and 14 days have passed since the exposure, you are safe to interact (note: the self-quarantine period remains 14 days, per CDC guidance).

If the family cannot get tested and remains without symptoms for the 14-days post-exposure, it’s also *likely* safe to interact, but please take as many public health precautions as possible (wear a mask and ask that everyone you meet with wear a mask, keep 6+ feet apart, meet outside, if possible). I make this “likely” statement based on two pieces of current knowledge: 1) This 14-day window is the outermost window that symptoms could appear; 2) People who are asymptomatic are not considered contagious 10-days after testing positive. In instances where there is no test, I’m assuming that the asymptomatic person would have tested positive a few days after exposure; add 10-days to that and we basically get to the 14-day self-quarantine window. The problem here, however, is knowing whether the exposed family member who becomes asymptomatic has in turn exposed other family members. Such exposure would basically reset the clock. All that to say, please encourage the family to get tested in addition to self-quarantine!

Q&A for 10/31:

#Rapid Testing #Reopening #Schools

Question: Doesn’t it seem like cheap, rapid testing is the best approach to getting kids back to school, and people back to offices and public events? It doesn’t have to be perfect, just good enough to identify most positive cases.

Answer: I agree that cheap, rapid testing is a key component of pandemic response, including for helping us return to work and school. As an intervention, however, it’s not sufficient. Rapid testing must be used alongside other public health measures, including masking and distancing, and in the case of school, podding. Last week, JAMA published an overview of the benefits and limitations of rapid testing, The Challenges of Expanding Rapid Tests to Curb COVID-19, which nicely lays out the pros and cons.

Pros include:

• Quick turn-around;
• Inexpensive (the aim is to have DIY tests for ~$1/test); and
• Identification of far more cases, especially those who are pre-symptomatic and asymptomatic.

Cons include:

• No DIY option yet (still need a health provider to give you the nasal swab and read results);
• Risk of false negative (discussed most recently in Q&A of 10/22 #Testing; additionally, most currently available rapid tests have not been evaluated specifically for performance in children or people who do not have symptoms);
• Potential for over-reliance on testing (for example, see CDC’s latest MMWR, “Outbreak at an Overnight Summer School Retreat” where testing was used to admit summer campers, no other public health measures were followed, and a huge outbreak occurred); and
• Human behavior is difficult to change (will people regularly self-test? correctly self-report?).

Johns Hopkins Center for Health Security and Duke-Margolis Center for Health Policy issued a report earlier this month, “Risk assessment and testing protocols for reducing SARS-Cov-2 transmission in schools,” which offers helpful guidance to schools based on different levels of community transmission and risk. As stated in the JAMA overview, “To assess the approach described in the report, The Rockefeller Foundation signed a memorandum of understanding with HHS, which is sending at least 120 000 Abbott BinaxNOW tests to 5 pilot areas: Louisville, Kentucky; Los Angeles; New Orleans; Tulsa, Oklahoma; and Rhode Island.” It will be fascinating to learn the results of these pilot tests to understand how rapid testing can help schools open and remain open.

Q&A for 10/30:

#3 Cs #Roses #Dogs

Question: This may seem trivial and myopic, but is there any risk of transmission when petting the neighbor’s dog or smelling their roses (which every passer-by does!)?

Answer: When it comes to minimizing risk, the clearest communication I’ve seen is from Japan (Figure 1). We’ve talked about risk many times, but remembering the 3 Cs — Closed spaces, Crowded places, Close-contact settings — is key for understanding which scenarios carry increased risk. There’s not going to be guidance for every type of daily activity — like smelling the roses — so I recommend using the 3 Cs to guide your risk calculation. Passing some fragrant roses? Check the scene. Closed spaces? Crowded places? Close-contact settings? If yes, avoid. If not, enjoy! Here’s a bit more information specific to the two examples you gave:

• Smelling the roses: I assume the issue is that other people may have had their faces close up in the blossoms, breathing on the petals, and presumably depositing their germs. I assume these roses are outside, so we can be confident that the virus dies quickly thanks to sun, wind and inhospitable conditions. If the 3 Cs aren’t present, we don’t need to worry about airborne transmission. Instead the worry is fomite transmission — from petal to your face and into your body. This scenario seems exceptionally unlikely. If you have a whiff of concern (see what I did there), make sure you don’t touch the flower with any part of your body, especially your face. If you avoid touching the rose with your nose, you’ll avoid any lingering risk, ever small as it may be.
• Petting the puppy: It’s always good, in COVID times and not, to wash your hands after petting an animal. Please be sure to wash your hands after petting the dog. We have no evidence of any dog transmitting the virus to any human, and for more on animals and COVID-19, see CDC’s guidance here.

Finally, one more important point. The risk of fomite transmission in most settings is very low. The virus cannot enter through your healthy skin. So, when we’re talking about fomite transmission, we’re generally talking about this type of scenario: virus particles are on your hands from having touched a germy surface; your hands then touch your mouth, nose, or eyes; the virus enters such an orifice and infects you. Thanks to the wonders of our skin, you don’t need to stop touching things (or petting dogs) — with regard to fomite transmission, as long as you wash your hands well and avoid touching your face after you touch that thing (or that dog), you’re well protected.

Figure 1. Avoid the 3 Cs (from Prime Minister’s Office of Japan)

Q&A for 10/29:

#Work #Box

Question: There has been talk about keeping desks 6 feet apart when we return to work. However, if we are all sitting in a poorly ventilated room together for hours, won’t we all be exposed to each other no matter how close or far our desks are from each other?

Answer: I’m picturing a poorly ventilated box the size of my kitchen. Let’s say there are four people in the box. If you spend enough time there, you’ll be breathing each other’s air no matter how far apart your standing/sitting. In that respect, your concern is correct. But if there’s a mandate that everyone in the box must stay at least 6 feet apart, then it limits the number of people in the box. Instead of 4 people in the box, now only 3 can fit. Your risk is greatly reduced because your box pod is 25% smaller. I think it’s this way with desk spacing too. It keeps the number of people in the room limited, reducing your pod size, and therefore reducing your risk. And please keep pushing for improved ventilation!

Q&A for 10/28:

#Symptoms #Onset #Smell

Question: Wondering about sudden onset of symptoms…..how common is it and what’s the most likely abrupt signal that you might be infected, constituting a medical emergency?

Answer: COVID symptoms can appear gradually in some individuals and suddenly in others. The main self-check that serves as an early sign of infection is loss of smell. I think about that when I smell my coffee in the morning… mmmmm coffee. Doctors warn (as does CDC’s clinical guidance) that mild symptoms can quickly turn serious. When it comes to medical emergencies, CDC recommends that you call 911 and seek emergency care immediately if you experience any of the following: trouble breathing, persistent pain or pressure in the chest, new confusion, inability to wake or stay awake, and/or bluish lips or face.

COVID Symptoms vs. Common Cold and Influenza Symptoms

We talked about COVID symptoms way back in our Q&A of 7/6 #Symptoms. Since then, more evidence has accumulated that loss of smell is a common symptom that often presents suddenly (pooled estimates suggest 44% of cases experienced loss of smell based on subjective measurements; 77% based on objective measurements). This symptom helps differentiate COVID from other widely circulating viruses, like the common cold or flu. Cough, fever, and shortness of breath are also common COVID symptoms (Figure 1). Fever helps differentiate COVID from the common cold. Still, there’s a lot of overlap with influenza symptoms. The journal, Frontiers in Public Health published in August, “Modeling the Onset of Symptoms of COVID-19,” which showed that COVID is more likely to begin with a fever while influenza is more likely to begin with cough and fatigue. That’s one more way to try and differentiate COVID from influenza. When it comes to symptom onset, colds usually come on gradually, flu usually comes suddenly, and COVID can come gradually OR suddenly. If you experience loss of smell, fever, cough, or shortness of breath, please be sure to call your doctor, who will likely recommend that you get tested for COVID. Obviously, if you have any other health concerns, call your doctor too!

Figure 1. Symptoms of COVID (from CDC)

Q&A for 10/27:

#Playgrounds

Question: This article from the Washington Post got me thinking about playgrounds. Some of my friends still won’t let their kids go play on a playground (even if other people there are masked). Do you think we finally have enough data to agree that playgrounds are safe?

Answer: The article, “Stop wiping down groceries and focus on bigger risks,” does a really nice job explaining the risks associated with fomite transmission under different scenarios. Experts remind readers that high traffic indoor places, like public restrooms adjoining an airport lobby, are much bigger risk for fomite transmission than outdoor places, including playgrounds. I checked the COVID Super-spreader Settings database that London School of Hygiene and Tropical Medicine researchers maintain to see if there were any playground settings listed. In promising news, no playgrounds were on the list! The upshot is, in the scheme of low- to high-risk activities, going to a playground *if you maintain good public health practices* would fit in the lower-risk category. Of course, it’s COVID times, so there’s still more risk than staying home, but participating in lower risk activities can be important for maintaining our health — physical, emotional, and mental. A bit more information:

• The risk of fomite transmission at playgrounds is low due to how quickly the virus dies in the outdoor environment. However, because playgrounds present the opportunity of lots of hands touching the same surfaces, frequent hand washing is imperative, as is avoidance of touching the face while at the playground (virus could move from hands to mouth, eyes, or nose).
• The risk of person-to-person transmission at the playground is higher if the playground is busy, making social distance difficult to maintain. Please follow good public health practices. CDC offers some guidance on visiting playgrounds here, and it’s mostly what you’d expect — don’t go if you’re sick; maintain 6+ feet of distance; wear masks; wash hands; avoid touching your face.
• Even though playgrounds are lower-risk settings and we have no evidence of transmission events from playgrounds, absence of evidence is not evidence of absence. Playgrounds have been associated with other disease transmission events. For example, exposure to public playgrounds has been associated with increased risk of hand, foot, and mouth disease. To minimize risk, it’s imperative to follow good public health practices, especially good hand washing practices!

Q&A for 10/26:

#Infectious Dose

Question: Per yesterday’s post, does this research suggest low exposure to the virus can provoke antibodies and some immunity to the virus?

Answer: Hmmmmm… maybe. Two big outstanding questions about COVID-19 remain — 1) How much virus does it take to make a person sick?; 2) Is the size of the infecting dose associated with the severity of disease? As discussed yesterday, some early research has shown that low exposure to the virus (e.g. exposure while wearing personal protective equipment) is associated with asymptomatic infection. People who are asymptomatically infected have similar viral loads as those who are symptomatically infected (see Q&A of 7/4 #Asymptomatic Transmission), which could mean that they go on to develop antibodies and other immune system responses that could confer future immunity. Unfortunately, it also means that they can unknowingly transmit the virus to others. Related, we have recent evidence showing that exposure to other types of coronaviruses does not confer any immunity to SARS-CoV-2 (note: this study is not yet peer reviewed).

Then we have the issue of defining “low exposure” since we still don’t know just how much SARS-CoV-2 virus it takes to make a person sick (e.g. the minimum infectious dose). Based on studies of other coronaviruses and influenzas, coupled with how quickly COVID spreads, experts think the minimum infectious dose is relatively small — perhaps 1,000 virons (e.g. 1,000 of the tiny SARS-CoV-2 virus particles). To put that in perspective, scientists estimate that one infected host cell can produce up to 1000 SARS-CoV-2 virons over the course of infection (Image 1). As reported in Science, “estimates using an average sputum viral load for SARS-CoV-2 indicate that 1 min of loud speaking could generate >1000 virion-containing aerosols. Assuming viral titers for infected super-emitters (with 100-fold higher viral load than average) yields an increase to more than 100,000 virions in emitted droplets per minute of speaking.” Masks keep the majority of these droplets from reaching your airway (Figure 1)! Again, this is why mask wearing, social distancing, and good ventilation are so important.

Image 1. SARS-CoV-2 (in blue) emerging from infected cell (from NIAID)

Figure 1. Masks reduce transmission (from Science)

Q&A for 10/25:

#Exposure Dose #Viral Load

Question: What’s the latest research on dose response for exposure to COVID-19 and what can it tell us about our risk choices?

Answer: We know that the more virus a person is exposed to, the higher their risk of being infected (for more background, see Q&A of 5/20 #Viral Load, Q&A of 5/12 #Risk). This is a big reason why public health experts recommend keeping interactions where social distancing isn’t possible as brief as possible (<15 minutes). Findings published last week in CDC’s MMWR also indicate that multiple brief exposures over 24 hours that cumulate in exposure time of 15+ minutes can result in infection, hence CDC’s recent “close contact” definition change (discussed in Q&A of 10/22 #Incubation). It’s also why mask wearing is so key! And why outdoors is safer than indoors.

When it comes to the relationship between initial exposure dose and disease outcome, we are far less certain as the science is still emerging. Some scientists have hypothesized that lower initial exposure dose could be an important factor for asymptomatic infection. And this perspective, “Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine,” published in the New England Journal of Medicine last month hypothesizes that by limiting initial exposure dose, mask wearing could “reduce the severity of disease and ensure that a greater proportion of new infections are asymptomatic.” Here are a few interesting findings, which point to the potential of a relationship between exposure dose and disease outcome:

• This article, “Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity” published in August in the International Journal of Infectious Disease concluded that “a greater viral inoculum at the time of SARS-CoV-2 exposure might determine a higher risk of severe COVID-19.”
• This article, “Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan” published last month in Clinical Microbiology and Infection concluded that healthcare workers “who performed tracheal intubation or extubation were most likely to develop related symptoms, whereas those taking aggressive measures, including consistent use of N95 masks and eye protection, tended to be asymptomatic cases.” These findings indicate that one reason for asymptomatic infection is that the infecting dose is smaller.
• This article, “SARS-CoV-2 viral load predicts COVID-19 mortality,” published in Lancet in August, found a significant independent relationship between higher viral load and increased risk of mortality. Here, viral load does not necessarily equate with initial exposure dose, so we can’t draw conclusions on that front, but nonetheless, it is in keeping with other pieces of evidence we’re seeing on the dose-response relationship.

Q&A for 10/24:

#Antigen Test #PCR #Transmission

Question: Curious about Trump’s COVID tests……If he tested positive when he was infected, how is it possible that the most recent test is negative, so soon after his hospitalization?

Answer: Short answer: It’s because they are using an antigen test.

Slightly longer answer: In order to identify when a positive person is no longer contagious, CDC recommends using symptoms-based strategy NOT a test-based strategy (Figure 1). The president’s doctors, however, seem to have used a test-based strategy to end his isolation. And the test they used is an antigen test, which is unlikely to present a positive result if 1+ week has passed since symptom onset (Figure 2).

Longest answer: Back on October 12th, the president’s doctor wrote a memo stating, “In response to your inquiry regarding the President’s most recent COVID-19 tests, I can share with you that he has tested NEGATIVE, on consecutive days, using the Abbott BinaxNOW antigen card.” More recently (October 22), White House chief of staff Mark Meadows told reporters that the president was tested aboard Air Force One en route to the debate and that the test came back negative. Given the circumstances of that most recent test, coupled with the 10/12 memo and what we know of the current White House testing strategy, I think we can confidently assume that the test aboard Air Force One was also the Abbott BinaxNOW antigen test. We talked about antigen tests, and the BinaxNOW tests specifically, in our Q&A of 9/18 and Q&A of 9/16 #Antigen Test. Basically, the antigen test will pick up the virus and show a positive result if you are in the late pre-symptomatic or early symptomatic phases of COVID. However, about 1 week post-symptom onset and thereafter, the antigen test will be increasingly unable to detect the presence of viral proteins and will return a negative result (Figure 2). On the flip side, had PCR tests been used, there’s a strong possibility that they would still return as positive because they can capture SARS-CoV-2 RNA for a long period of time, much longer than a person is contagious. For these reasons, CDC “does not recommend using antigen tests to make decisions about discontinuing isolation.” Furthermore, CDC’s interim guidance states, “A [PCR] test-based strategy is no longer recommended (except as noted below) because, in the majority of cases, it results in prolonged isolation of patients who continue to shed detectable SARS-CoV-2 RNA but are no longer infectious.” So really when it comes to understanding whether the president was/is contagious while interacting with others, we’d need to know timing of symptom onset, timing of last fever, and symptom improvement.

Figure 1. Symptoms-based strategy for identifying when a patient is no longer at risk of transmitting the virus to others (from CDC)

Figure 2. Probability of Positive Result by Test Type (from Nature)

Q&A for 10/23:

#Family #Thanksgiving #Holidays #Harm Reduction

Question: With Thanksgiving coming up, what advice do you have for safely spending the holidays with family?

Answer: I talked some about family visits way back in Q&A of 5/29 #Family [Note: Medium is not all that user friendly for finding old posts. When you click on the embedded link, do a word search for #Family and you’ll quickly come to the 5/29 post.] With the holidays approaching and community transmission on the rise, it remains an important topic. Yesterday, Dr. Lena Wen wrote an opinion piece in the Washington Post that describes some of the issues and mitigation measures a person/family could take. Here’s a list of the most to least safe ways to celebrate:

1. The most stringent approach is have in-person Thanksgiving with those you live with and virtual Thanksgiving with everyone else. I know a lot of folks won’t choose that option.
2. The next most stringent approach is to ask everyone who is attending to self-quarantine for 14 days before Thanksgiving and get tested shortly before coming. In this scenario, for example, going to the grocery store would be fine, but going to a restaurant would not. For plenty of folks, especially those with college kids coming home, those who work outside the home, and those who have kids physically back in school, this approach is untenable.
3. Next up is the harm mitigation approach most of us are more likely to try. Here we must remember that increased risk comes with more people in confined spaces with limited air circulation. So to limit risk:

• Limit the number of attendees (and try not to get your feelings hurt if some guests opt out of coming or if you’re not invited this year!);
• Be sure no one comes (and you don’t host) if they/you have been recently exposed or have been feeling unwell;
• Keep Thanksgiving outdoors;
• Keep folks sitting and mingling more spaced than usual;
• Avoid close contact, including hugs and close talking
• Avoid loud talking or shouting (like when your uncle gets really into a football game and starts shouting at the tv!; no! if possible, keep the football off!)
• Have one person serve the meal (to limit different people touching serving utensils);
• If you can’t have Thanksgiving outdoors, try to keep the windows open and air circulating inside to avoid stagnant air and the possibility of airborne transmission;
• If guests are indoors, including to use the restroom, have them wear masks (of course, they’ll need to remove them to eat.)
• If guests can’t keep 6+ feet of distance outdoors, have them wear masks.
• CDC offers a few more tips for gatherings here.

Q&A for 10/22:

#Testing #Incubation

Question: If I think I may have been exposed to COVID, how long should I wait to get tested?

Answer: We’ve talked a bit about this in previous posts (see Q&A of 9/18 #Antigen Tests, Q&A of 7/12 #Timeline, and Q&A of 7/3 #False Negative). Based on what I’ve read,the best time to get tested is as soon as you feel symptoms OR 3–5 days after exposure (if you aren’t experiencing symptoms). Here’s a quick synthesis:

Timeline: The median time of symptom onset is 5 days after exposure (range: 2–14 days). People can transmit the virus before showing symptoms, as early as 2 days after exposure. Yesterday CDC updated its “close contact” definition, which is now “anyone who was within 6 feet of an infected person for a total of 15 minutes or more [over a 24-hour period].” If you have reason to believe you were exposed (e.g. in close contact), please self-quarantine, and if possible, get tested.

Testing: Three things we can be confident about and one thing we’re less confident about:

1) If you test the day of exposure, you’re sure to get a negative result, even if the virus has begun circulating in your body.

2) If you test the day of symptom onset and you are infected with SARS-CoV-2, you’re very likely to get a positive result.

3) If you test several days after symptom onset, it’s better to use a PCR test rather than an antigen test; when using a PCR test you’re also very likely to get a positive result if you are indeed infected.

4) If you are pre-symptomatic or asymptomatic, the best time to test post-exposure is less clear cut. Based on what I’ve read, 3–5 days after exposure is likely the best time to get tested, but a negative result isn’t a guarantee that you’re truly negative, so please continue to take precautions and consider getting yourself retested later in the 14-day incubation window.

Q&A for 10/21:

#Flu #Influenza #Trends

Question: What are the rates of flu right now? Is the flu going up as well?

Answer: CDC keeps track of seasonal influenza spread in the US and shares its findings here. As of the latest data — week 41, ending 10/10 — “Seasonal influenza activity in the United States remains low.” Only two states have moderate levels of influenza activity — West Virginia and Iowa. It’s still way too early in the flu season to make heads or tails of influenza rates for the 2020–21 season. We’d expect flu to be low in October (see recent trends in Figure 1) and to be increasing as the flu season progresses. In the meantime, we can look at recent influenza trends in the US over the Spring/Summer “interseasonal” period and also look at recent trends from the southern hemisphere, which already experienced the height of this year’s influenza season.

Good news! According to a report recently published in CDC’s MMWR, “the percentage of U.S. respiratory specimens submitted for influenza testing that tested positive… has remained at historically low interseasonal levels (0.2% versus 1–2%). Data from Southern Hemisphere countries also indicate little influenza activity.” Scientific American published a short piece on this very topic a few weeks ago, quoting Greg Poland, an influenza expert at the Mayo Clinic who stated, “Never in my 40-year career have we ever seen rates … so low.” He goes on to describe how continuation of key public health measures could lead to the most dramatic drop in influenza cases in modern history (see Figure 2 for trends from South America). Even so, please go get your flu shot!

Figure 1. Seasonal Influenza in the USA, Week 41 of 2020–21, 2019–20, and 2018–19 influenza seasons (from CDC)

Figure 2. Seasonal Influenza trends in South America (from Scientific American)

Q&A for 10/20:

#TX #KY #Trends

Question: Please run the numbers for Texas! And Kentucky!

Answer: Sure thing! Here are charts for Texas and Kentucky that I made using data from covidtracking.com. All of the numbers I am mentioning are 7-day rolling averages.

Texas. Daily tests have plateaued around 60,000 tests/day since early September. Meanwhile, test positivity has remained stubbornly high (currently 7.1%), which indicates that testing is not keeping pace with community spread. Daily cases are again on the rise (4,364 cases/day), as are current hospitalizations (4,216 hospitalized). Daily deaths have been on the decline since their peak in early August, but with hospitalizations again on the rise, we can expect to see deaths reverse course in the coming weeks.

Kentucky. Daily tests have been increasing over time (19,000 tests/day), as have cases (1,045/day), hospitalizations (709 currently hospitalized), and deaths (10/day). The increase in cases is not simply a result of increased testing; test positivity is also high and on the rise (5.2%) and hospitalizations have been increasing. Kentucky is currently experiencing the highest daily rates of cases, hospitalizations, and deaths since the pandemic began.

Figure 1. Texas

Figure 2. Kentucky

Q&A for 10/19:

#Cleaning

Question: I have an apartment that I rent to folks via Airbnb. I’m trying to follow all of the coronavirus cleaning protocols, but it’s not clear to me whether Airbnb is really following protocols or using this as an opportunity to push their *new line of cleaning products*! Is there a codified set of protocols I can reference from some ideally non-biased group, like CDC or WHO or something? For example, in addition to the standard cleaning protocols like sterilizing and frequently wiping down every surface, Airbnb is asking us to leave 24 hours between each rental and follow a long list of cleansing routines, such as washing curtains and sanitizing every dish and pot and pan each rental. Am I really supposed to take the curtains down and wash them between every rental? What about the carpets then?

Answer: When profit and health collide, it’s hard to disentangle what is necessary vs. nice. CDC does offer a set of guidelines for hotels, resorts, and lodges, which I think would apply to short-term rentals as well. CDC also offers these guidelines for “cleaning and disinfecting your facility”, which would also likely be applicable to your situation. In reading through these guidelines a few things leap out:

• The guideline re: 24 hours in between rentals seems only to apply in the case of a sick renter. IF someone has been sick in the space, wait at least 24 hours or as long as possible to enter in order to clean and disinfect after the person has checked out. And IF you had a sick renter, then more complex cleaning protocols should be followed, like cleaning the carpets with a vacuum equipped with a HEPA filter (note: there are many vacuums that have HEPA filters and they aren’t all that expensive). There are no other guidelines (to my knowledge) about other wait times in between rentals (e.g. when the person who checked out was well).
• For disinfectant, you can use any typical household cleaner on EPA’s List N, which includes bleach (which you can dilute as an effective disinfectant, per CDC guidelines). You can look up the products you have and see if they are on the list.
• For soft surfaces, like curtains, CDC suggests that you either clean and launder them OR use a household disinfectant (see “soft surfaces” here).

Please take a read through and hopefully the guidance provided will answer your questions. Good luck!

Q&A for 10/18:

#Trends #USA #NYS #DC #MD #VA #TN

Question: How are things looking in New York and elsewhere?

Answer: You’ve probably been reading about how much of the US is witnessing an upswing in COVID cases and hospitalizations. It’s been about a month since we looked at the trends, so let’s take another peek. All of the numbers I’ve written herein are 7-day rolling averages; data are from covidtracking.com. I sometimes run numbers for Texas and Kentucky, but didn’t get around to it this morning. If you want to see those, just let me know.

Figure 1. USA: It’s bad. Approaching July peaks of daily cases (55K new cases/day); hospitalizations are on the rise (36K currently hospitalized); test positivity rate is above the 5% threshold (5.3%); and daily deaths are numbering 700. The only positive I see is that testing continues to increase.

Figure 2. NYS: After months of keeping transmission rates very low, New York is seeing an increase in the spread of COVID with new daily cases (1.4K) as high as late May; number currently hospitalized (900) the highest since the beginning of July and daily deaths (10) the highest since late July. Test positivity rate (1.1%) is still low, but New York needs to act quickly to contain further spread.

Figure 3. DC: After experiencing a downward trend in cases and hospitalization, DC witnessed an uptick earlier this month that (fingers crossed) seems to be squelched.

Figure 4. Maryland: Maryland is again experiencing an uptick in cases and hospitalizations with daily new cases (600) as high as they were in mid-September and number currently hospitalized (400) as high as late-August.

Figure 5. Virginia: Virginia is also trending in the wrong direction with daily cases as high as they’ve ever been (~1,050/day) and current hospitalizations on the rise (~1000). Test positivity is above the 5% threshold (e.g. widespread community transmission not fully picked up by tests).

Figure 6. Tennessee: Perhaps worst of this set of five states+district, Tennessee’s daily cases (1.9K) are as high as early August and numbers currently hospitalized (1.2K) are as high as mid-August. Daily test numbers have been relatively stagnant and test positivity (8.2%) is as high as early August. Meanwhile, unlike the other states in this set where deaths have not (yet) risen, daily deaths in Tennessee (21) are generally trending up.

Figure 1. USA

Figure 2. NYS

Figure 3. DC

Figure 4. Maryland

Figure 5. Virginia

Figure 6. Tennessee

Q&A for 10/17:

#Protests #Rallies #Risk

Question: Do you think having 6–10 thousand people coming for a March in DC is a huge COVID risk for our city and residents?

Answer: Having people descend on our city from other places — especially places with higher transmission rates — is no doubt a challenge. But given what we’ve learned from other recent protests and marches, if people keep their distance, wear masks, keep moving, and minimize shouting, the risk should be minimized. And because locals tend to modify their behavior during protest events by staying home and avoiding crowds to a greater degree, the risk is further minimized. For example, evidence on the relationship between Black Lives Matter protests and COVID transmission rates compiled and analyzed by the National Bureau of Economic Research concludes, “we find no evidence that urban protests reignited COVID-19 case or death growth after more than five weeks following the onset of protests. We conclude that predictions of population-level spikes in COVID-19 cases from Black Lives Matter protests were too narrowly conceived because of failure to account for non-participants’ behavioral responses to large gatherings.”

Are public health professionals hypocrites?

I’d also like to take a moment to talk about a difference in how public health folks talk about the risks of protests/marches versus the risks of rallies. I can see how some people may think that there is political bias in the way in which public health folks seemingly support protests/marches (seen more on the political left) while seemingly rail against in-person rallies (seen more on the political right). Is this stance hypocritical? Answer: No. Unlike the protests/marches that we’ve seen throughout the summer and fall in support of Black Lives Matter, we’ve seen that in-person political rallies — while outdoors (good) — are closely packed, with limited mask wearing, lots of shouting, and limited movement (bad). Limited public health measures at rallies have resulted in increased community spread of COVID. As reported in STAT News yesterday, “Spikes in Covid-19 cases occurred in seven of the 14 cities and townships where these [Trump] rallies were held: Tulsa; Phoenix; Old Forge, Penn.; Bemidji, Minn.; Mankato, Minn.; Oshkosh, Wis.; and Weston, Wis.” (Figure 1). Upshot here is that the difference in public health discourse around protests/marches and rallies is about the difference in behaviors witnessed at such events and the risk associated with such behaviors. Public health experts express increased alarm towards rallies because they are more risky and that risk has translated into more community spread.

Do public health professionals have personal beliefs?

This may be a silly question, but two personal views often get wrapped into these discussions (enumerated below), muddying the water about public health bias. These personal views make the discussion about risk more challenging because they move the conversation outside of the sole space of science (which we generally try to keep apolitical). My paragraph above is about the evidence to date, which shows that public health professionals are not being hypocritical. I’m writing this final paragraph because I want to acknowledge that additional viewpoints often show up within the public health discourse. Yes, public health professionals, like every individual, have personal beliefs. Would public health communication aimed at bridging political divides be better if personal beliefs were left out of the discussion? Given the current context, I honestly don’t know.

1. The pushback against rallies is also a push for our leaders to model and support good public health behavior.
2. Most public health folks (including me) see a difference between recent protests/marches and rallies in terms of the risk/reward calculation and the hierarchy of needs. In short, because protests/marches are people peacefully gathering to actively push for justice in light of police brutality (e.g. basic needs) while rallies are people peacefully gathering to actively support a political candidate (e.g. psychological needs), the rewards of protests/marches seem more worthy of the risk.

Figure 1. Spikes in COVID Cases following Trump Rallies (from STAT News)

Q&A for 10/16:

#Recovery

Question: What do we know about COVID survivors? Are long-term complications really all that common?

Answer: We talked about this a bit in our recent Q&A of 10/5 #Recovery. Yesterday, the UK’s National Institute for Health Research published a very informative report, “A dynamic review of the evidence around ongoing Covid19 symptoms (often called Long Covid).” This offers a more robust synthesis of the limited evidence to date on longer-term issues for recovery (see evidence bulleted below), highlighting that the outcomes of COVID-19 disease are not the binary (death/recovery) that many of us assume; rather “recovery” can be a long road with various challenges. For many of those with severe COVID, the road to recovery is likely long, and for a substantial proportion (~10%) of those with mild/moderate COVID, symptoms may last for >4 weeks.

One of the main findings of the team of researchers and doctors who reviewed the current evidence and interviewed patients to inform this report is — “Long covid” does not seem to be one syndrome and the long-term effects of the multisystem disease may instead manifest as different syndromes, including post-intensive care syndrome, post-viral fatigue syndrome, and/or long-term covid syndrome. As report author, Elaine Maxwell, said in an interview with BMJ News, “We are not saying that we have identified four definitive syndromes. We are raising this as a possibility and a possible explanation for why so many people feel they are not being believed or heard and are not getting access to supportive treatments.”

Evidence of Long Covid (quoted from NIHR report)

• “A team from Italy, one of the earliest affected countries, reported that 87% of people discharged from a Rome hospital were still experiencing at least one symptom 60 days after the onset on Covid19 and 55% had three or more symptoms including fatigue (53%), difficulty in breathing (43%), joint pain (27%), and chest pain (22%) with 40% saying it had reduced the quality of their life.
• On 5th June 2020, NHS England published ‘After-care needs of inpatients recovering from COVID-19’. This estimated that up to that date, more than 95,000 patients had been admitted to hospitals across England with Covid19 and it assumed 45% would need ongoing support.
• Some estimates suggest that up to 50% of people hospitalised would need formal rehabilitation services.
• An unknown number of people have had Covid19 symptoms (both with and without access to a test) and self-cared at home. Public Health England published guidance on 7th September 2020 stating that around 10% of ‘mild’ Covid19 cases who were not admitted to hospital have reported symptoms lasting more than four weeks and a number of hospitalised cases reported continuing symptoms for eight or more weeks following discharge.
• Similar findings are reported by a patient group who surveyed a self-selected sample of 640 people with symptoms lasting over two weeks (respondents were predominantly US-based white females and not hospitalised at any time). The vast majority of participants experienced fluctuations in the type of symptoms (70%) and the intensity of symptoms (89%) over time.
• The UK Covid Symptom Study app has over 4 million regular contributors and suggests that a ‘significant number’ of people report symptoms for a month and between 10% and 20% report complications for longer.”

Q&A for 10/15:

#Blood Type

Question: I read some headlines again mentioning blood type and COVID. What’s the latest?

Answer: We last talked about blood type and COVID in our Q&A of 6/23 #Blood Type. A new study was published in the New England Journal of Medicine just today that sheds more light on the association between blood type and severe COVID outcomes, “Genomewide Association Study of Severe Covid-19 with Respiratory Failure” (described further in the paragraph below). Similar to what we discussed back in June, authors report, “In the meta-analysis corrected for age and sex, we found a higher risk among persons with blood group A than among patients with other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10−4) and a protective effect for blood group O as compared with the other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10−5)….Our genetic data confirm that blood group O is associated with a risk of acquiring Covid-19 that was lower than that in non-O blood groups, whereas blood group A was associated with a higher risk than non-A blood groups.”

In this case-control study, researchers recruited 1980 patients with severe Covid-19 — defined as hospitalized with respiratory failure (e.g. oxygen supplementation or mechanical ventilation) and COVID-19 confirmed with positive PCR test — from seven hospitals in Italy and Spain (cases). They also recruited 2381 control participants from Italy and Spain, the majority of whom were healthy blood donors (controls). Researchers then extracted DNA from participant samples and compared genomic sequencing between cases and controls to understand whether people who experienced severe COVID-19 had genetic susceptibility — controlling for age, sex, and underlying conditions — comparing those with the most severe outcomes (mechanical ventilation) with less severe outcomes (oxygen supplementation) AND comparing all cases with all controls.

Q&A for 10/14:

#Reinfection #Vaccination

Question: I read this article from NPR, “Scientists Confirm Nevada Man Was Infected Twice With Coronavirus,” with interest and disappointment. If it’s proven that folks can get reinfected with the virus just a couple months after the first infection, doesn’t this bode poorly for the efficacy of a vaccine?

Answer: This Monday, Lancet published a case study of the first confirmed COVID-19 reinfection in the United States. This case study adds to a small but growing body of evidence that reinfection can occur. In my opinion, the main take-away is that even if you have already been infected with SARS-CoV-2, you should still continue to practice public health prevention measures — masks, distancing, hand washing. When it comes to vaccines, the take-away is less clear cut; I suggest setting aside your disappointment until we know more. Here’s the deal, as synthesized from an accompanying commentary that Lancet published, “What reinfections mean for COVID-19,” as well as an article published in Scientific American three weeks ago, “What COVID-19 reinfection means for vaccines,” and an article published in Nature last month, “Coronavirus reinfection: three questions scientists are asking.”

• What are the odds of reinfection? So far, we have very few case studies to draw inferences from (N=5). Is this because reinfection is truly extremely rare or because we are only now in a position to experience and monitor reinfection (because time has elapsed, 2nd waves are occuring, and testing/genomic analysis systems are more widely available)? We need more time and data to know the answer. Based on current evidence, the odds of reinfection seem miniscule, but absence of evidence is not evidence of absence. Reinfection for other types of coronaviruses is the norm.
• Why does reinfection occur? We don’t know. One hypothesis is that reinfection occurs in those who have limited antibodies after first infection. Another is that antibody response quickly wanes, leaving an individual unprotected against future exposure. We need to measure the level of antibodies present at time of reinfection to test these hypotheses.
• Are people less likely to experience severe disease upon reinfection? So far, it’s a mixed bag. Of the five cases, two experienced more severe disease upon reinfection. Of course, there are likely a number of people reinfected asymptomatically, who likely wouldn’t show up in estimates, so these few cases we have monitored are already biased towards those with severe disease and come to the hospital. Among the two cases who did experience more severe disease upon reinfection, we still don’t know why. Were they exposed to higher levels of the virus? Were there changes to their underlying health? Did a variant of SARS-CoV-2 produce more severe disease? Did their immune system somehow make things worse, like through an antibody-dependent enhancement? We need more data.
• Does infection by different viral isolates mean we need a vaccine for each type? As written in the Lancet commentary, “There is currently no evidence that a SARS-CoV-2 variant has emerged as a result of immune evasion. For now, one vaccine will be sufficient to confer protection against all circulating variants. Furthermore, reinfection by a distinct viral variant from the original virus does not imply immune escape.” Note: “immune escape” aka “immune evasion” is the ability of a virus to evade a person’s immune system and continue to grow/spread.
• Can those who are reinfected spread the virus to others? Limited data point to yes, based on viral load detected among those reinfected. We do not, however, have any case studies of a reinfected person transmitting infection.
• What does reinfection mean for vaccine development? We need more information on reinfection to really answer this question. That said, based on what we currently know, it’s looking possible that we may need to have booster shots as our immunity wanes and/or we may need to have new generations of the vaccine to respond to new variants (as we have with flu). These developments would mean more logistic hurdles, which are surmountable. If we do see far more reinfections and more severe outcomes upon reinfection, the possibility that SARS-CoV-2 tampers with our immune memory increases, and this would have far more problematic vaccine ramifications. Given the vaccine trials underway and the safety data collected to date, this possibility seems extremely unlikely. Finally, vaccine induced immunity is more powerful than immunity induced by natural exposure. As Yale professor of immunobiology, Dr. Iwaskai, told NPR, “The good thing about a vaccine is that it can induce much better immunity, a much longer lasting immunity, than the natural exposure to the virus.” If we’re lucky, one shot will do the trick!

Q&A for 10/13:

#Schools #Reopening #Superspread

Question: I was recently reading that the latest evidence on school reopenings shows that “schools aren’t superspreaders.” What do you think?

Answer: I read that Atlantic piece with interest too! For those of you who haven’t read it, the upshot is that based on preliminary survey data that Brown University economics Emily Oster has been collecting in partnership with Qualtrics online survey platform company, schools (grades K-12) are seeing infection rates generally slightly lower than local community infection rates. This is very heartening news. My major thought (described further herein) is that schools can be sites of superspreader events, but that risk is greatly mitigated based on the measures schools implement to keep their school community safe. When we put our effort and resources to it, we can protect our kids, teachers, and ourselves!

You can access the Qualtrics dashboard here and the most recently findings are further described in this recent Insider article (formerly Business Insider). The most recent data stem from 1,268 schools that have opted into the twice monthly survey. As I understand it, the survey is completed by the school principal, who answers questions in the baseline survey about student enrollment, reopening policy, mitigation measures used and answers questions about new infections and any changes to policy/mitigation measures in bimonthly follow-up surveys. When it comes to preliminary findings, I have the following thoughts:

1. We generally see super-spreader events when we have a COVID-positive individual (oftentimes before they are showing symptoms, but at the height of viral shedding) mixing with a crowd of people indoors with poor ventilation, oftentimes in loud settings, and with limited mask wearing. Schools may OR may not have environments that elevate super-spreading risks. It all depends on: a) the baseline condition of the school environment (ex: overcrowding); b) the mitigation measures schools have implemented (ex: universal mask wearing); and c) level of community spread (ex: the risk that someone in school will come to school infected). In the context of mask-wearing, good ventilation, small cohorts of students working together with their teacher the risk of super-spreading events would be low. And I think this is what the data are showing us. Yay!
2. That said, we do have examples of schools as the site of superspreader events. Here’s a database of superspreader events from around the world from researchers at London School of Hygiene and Tropical Medicine. And yes, schools K-12 do show up on the list. Schools can be sites of superspreader events, but that risk is greatly mitigated based on the measures schools implement to keep their school community (students, teachers, other school professionals) safe.
3. Finally, I’m having trouble finding the Qualtrics survey methods. Based on what I have read, their survey does not appear to be a representative sample survey but instead a convenience sample of schools that have opted in. According to the National Center for Education Statistics, as of 2010, there were >138,000 public and private K-12 schools in the US. With <0.1% of schools participating in the Qualtrics survey and with those schools being self-selected (rather than being randomly chosen based on robust statistical sampling design), I would not put much weight on extrapolating these findings to a set of schools beyond those included in this survey. For example, if the sample is biased (say, more schools that are implementing multiple mitigation measures are participating OR more schools in areas with low community transmission are participating, etc.), then the overarching finding — that schools are not the sites of superspreader events — may not hold true for the broader school population.
4. All that said, the fact that the schools participating have avoided superspreading events is something to cheer. It shows us — like the NBA bubble — that when we put our effort and resources to it, we can protect ourselves.

Q&A for 10/10:

#Treatments

Note: I will be traveling 10/11 and 10/12, so no daily updates. Happy Indigenous People’s Day!

Question: While we know widespread distribution of a vaccine will probably take a year or more, I would expect the use of the therapeutics to increase much faster. What do we think those treatments will be able to do to the death counts?

Answer: As discussed in our Q&A of 9/26, case fatality has declined over time. This decline is due to: a) increased testing; b) cases shifting younger; c) improved biomedical treatment. We should expect that patient treatment will continue to improve over time thanks to medical/therapeutic advances and health care worker/system’s growing experience, which means that the case fatality rate should continue to decline.* Here’s yet one more reason to try to avoid the coronavirus for as long as possible! When it comes to therapeutics and medical advances, the NY Times keeps a “Coronavirus Drug and Treatment Tracker” that I find quite helpful as a snapshot of what we currently know. For example, in terms of what works, we now know that:

• Remdesivir use among hospitalized patients has been shown to reduce duration of hospitalization
• Prone positioning on belly is effective at keeping oxygen levels up, reducing the need for ventilators.

*Note: A decline in the case fatality rate does not necessarily mean a decline in death counts since the number of deaths will greatly depend on the number of cases.

Q&A for 10/9:

#K #Overdispersion #Cluster Busting

Question: I thought this article, “K: This Overlooked Variable Is Key to the Pandemic,” was really insightful about our approach to the pandemic. I guess the question is, what are your thoughts on what this might look like in practice (here in the US)?

Answer: Thanks for sharing the article from The Atlantic. I also thought it was insightful. For those of you who haven’t read it, here are the main points (but the article is way more informative and interesting, so please read it!):

• Instead of spreading in a steady manner (like seasonal flu), SARS-CoV-2 spreads in bursts, where one person infects many (e.g. superspreading events). Enter ‘k’, a measure of dispersion. COVID-19 is overdispersed. Its “highly skewed, imbalanced distribution means that an early run of bad luck with a few super-spreading events, or clusters, can produce dramatically different outcomes even for otherwise similar countries.”
• To stop the spread of COVID-19, we have to focus on superspreading events — focus attention on the cluster bursts rather than the individual infections. [Note: the author points out that super-spreading events overwhelmingly occur in poorly ventilated indoors environments with many people over an extended period of time, especially where there is loud talking or singing. Sound familiar? It’s the same set of conditions as the airborne transmission risks we talked about yesterday!
• Recognizing the nature of COVID-19 transmission, we need to adapt our response:
• Target potential clusters. Keep prohibitions on crowded, indoor events. Mandate mask wearing indoors.
• Refocus contact tracing. Right now, if you’re positive, contact tracers will generally focus on finding everyone you interacted with in the previous 2 weeks to warn them and ask them to test and self-isolate (prospective tracing). Instead, contact tracing should focus on finding who infected you and then trace forward all of their contacts (retrospective tracing). In doing so, contact tracers are more likely to find positive people and stop the cluster from blossoming.
• Focus on rapid, cheap tests. For clustering, overdispersed transmission, speed is more important than accuracy. Instead of focusing testing on more accurate, but more time consuming PCR tests, we should make widespread use of rapid tests. These rapid tests will let us identify cluster events (more important than identifying infected individuals); the moment we suspect a cluster event, we can then use more precise testing while asking those who were at the event to self-isolate.
• Use wastewater testing. Like a canary in the coal mine, wastewater testing can give us a signal that either there are likely no infections or that there is a potential cluster, in which case we need to ask folks, especially in congregant settings, to self-isolate and test.

In the United States, I think the big switch in our approach would be this switch to “cluster busting.” This means that our focus would need to shift to preventing, detecting, and mitigating collective risks/transmission events, rather than individual-level risks/transmission events approach we currently take. The bullets above describe what this approach would look like. We’d need to have more standardized guidance to limit indoor, crowded events and mandate mask wearing, particularly indoors. We’d need to increasingly rely on rapid tests and wastewater testing and take swift action as soon as we get the signal from such tests of a potential cluster. And, we’d need to refocus contact tracing efforts on identifying where a cluster event took place and finding everyone at that event to ask them to test and self-isolate to keep the virus from spreading.

Q&A for 10/8:

#Airborne Transmission #Plexiglass

Question: Is plexiglass actually effective in deterring COVID-19? While it may protect against direct spray, isn’t one of the big issues virus traveling due to air circulation, which means that unless you’re quite literally encased in a box, you’re still facing exposure?

Answer: You’re right; in the context of last night’s debate, plexiglass probably did nothing. Where plexiglass comes in handy is for limiting droplet transmission in close quarters (like a pharmacist giving you your prescription). However, since the two people on stage were seated 12 feet apart, it’s unlikely that the plexiglass would have served as a barrier to droplet transmission — the droplets just wouldn’t have been propelled that far. So now what we’re talking about is whether plexiglass helps prevent airborne transmission. And in that case, plexiglass as used in last night’s debate was ineffective — it would not have stopped tiny droplets that float through the air. Mind you, to cause infection, these tiny droplets would have needed to accumulate, which is where ventilation comes into play. Indeed, the airborne transmission events we’ve observed have generally included the following factors: indoors, poorly ventilated, prolonged exposure (>15 minutes), and oftentimes loud (incl. people shouting/singing). If you want to read more, here are a few resources and articles you might find informative:

• CDC’s recent scientific update that “Airborne transmission of SARS-CoV-2 can occur under special circumstances.”
• American College of Occupational and Environmental Medicine plexiglass overview
• Quartz article from 10/7, “What do plexiglass dividers do to stop Covid-19?”
• NY Times article from 10/7, “Plexiglass Barriers Won’t Stop the Virus at the Debate, Experts Warn”
• Reminder: for a bit more background on airborne transmission, see Q&A of 7/18 and 7/17 #Airborne Transmission.

Q&A for 10/7:

#Influenza #Flu #Vaccine #Deaths Averted

Question: This infographic from Politico got me to wondering, if it weren’t for the flu vaccine, how deadly would the flu be?

Answer: I added the Politico infographic below for ease of reference. Good news [for making my job answering this question easy!] is that CDC’s Influenza Division estimates the burden of flu illness and death averted by vaccination in the United States. As CDC reports, “during 2018–2019, flu vaccination prevented an estimated 4.4 million influenza illnesses, 2.3 million influenza-associated medical visits, 58,000 influenza-associated hospitalizations, and 3,500 influenza-associated deaths.”

The number of infections and deaths averted will change yearly, largely depending on a) the severity of the flu; b) the vaccine effectiveness; and c) vaccine coverage. For example, the seasonal flu had high severity in 2017–2018, with CDC finding that “an estimated 8000 (95% CrI, 1100–21 000) influenza-associated deaths were prevented by vaccination (9% of expected deaths, overall; 95% CrI, 1%–20%). Influenza vaccination prevented an estimated 39% (95% CrI, 30%–45%) of influenza-related mortality in children aged 6 months–4 years.” If you want to read more, this paper published last year in Clinical Infectious Disease gives an overview of how such estimates are made and provides more detail on the 2017–18 flu infections averted, “Effects of Influenza Vaccination in the United States During the 2017–2018 Influenza Season.”

I suppose the upshot here is that if we were to try to compare apples to apples (e.g. two viruses that don’t have vaccinations), we’d still find that COVID is far more lethal than seasonal influenza.

Figure 1. COVID-19 is more deadly than seasonal flu (from Politico)

Q&A for 10/6:

#Dexamethason #Treatment #Corticosteriods

Question: What is the story with dexamethasone?

Answer: Dexamethasone is making a lot of news as a component of the drug therapy recently given to the President. Dexamethasone is a potent, long-lasting (24 hours) corticosteroid that is approximately 25x more potent than hydrocortisone. The main mechanism that corticosteroids are thought to help reduce COVID severity is that they reduce inflammation by tamping down the immune system so that it doesn’t attack itself (a la the cytokine storm we’ve learned about). Many questions still abound with regard to dexamethasone, but two recent studies — a clinical trial out of the UK and a meta-analysis conducted by the WHO — both indicate that dexamethasone can improve outcomes for patients with severe COVID-19.

Based on current evidence, WHO strongly recommends “for systemic (i.e. intravenous or oral) corticosteroid therapy (e.g. 6 mg of dexamethasone orally or intravenously daily or 50 mg of hydrocortisone intravenously every 8 hours) for 7 to 10 days in patients with severe and critical COVID-19…” and WHO also makes a conditional recommendation “not to use corticosteroid therapy in patients with nonsevere COVID-19.” As to non-severe COVID-19, one of the major concerns is that if given corticosteroids too early, the immune system could be hampered from doing its job and the patient would have a harder time fighting the virus.

Finally, if you want to read more, this JAMA editorial gives a good, brief run-down of the evidence and outstanding questions; this piece published in The Conversation gives a good overview of corticosteroids and COVID-19; and this Q&A from WHO gives more bite-sized information.

Q&A for 10/5:

#Recovery

Question: Among those who recover, what proportion have long-term symptoms? How about by age — like the charts from Friday?

Answer: The problem with understanding long-term consequences is that it requires time. Given where we’re at the pandemic, it’s still a bit too early to know long-term consequences, especially broken down by age. That said, it does appear that younger age is protective against long-term symptoms. And as would be expected, long-term symptoms are associated with disease severity. Here’s a bit of an update on what we currently know:

• Recovery takes time. As published in CDC’s MMWR, based on data collected through a telephone survey of individuals who were COVID positive and symptomatic, researchers found that after 2–3 weeks of testing positive, “35% had not returned to their usual state of health…. Among persons aged 18–34 years with no chronic medical conditions, one in five had not returned to their usual state of health.” (Figure 1)
• Hospitalized patients may suffer long-term lung and heart damage. The European Respiratory Society reported preliminary results from an Austrian study of hospitalized patients (primarily older, men, more likely to be smokers) that found at 6-weeks post-discharge,” more than half of the patients had at least one persistent symptom, predominantly breathlessness and coughing, and CT scans still showed lung damage in 88% of patients. However, by the time of their next visit 12 weeks after discharge, the symptoms had improved and lung damage was reduced to 56%…. At the six-week visit, the echocardiograms showed that 48 patients (58.5%) had dysfunction of the left ventricle of the heart at the point when it is relaxing and dilating (diastole). Biological indicators of heart damage, blood clots and inflammation were all significantly elevated.” CDC describes both lung and heart problems in its public webpages on long-term effects of COVID-19.
• Chronic fatigue is increasingly reported. This article published a couple of weeks ago in Nature, “The lasting misery of coronavirus long-haulers” offers a great synthesis of what we know and don’t know. As reported, “One study of 143 people with COVID-19 discharged from a hospital in Rome found that 53% had reported fatigue and 43% had shortness of breath an average of 2 months after their symptoms started. A study of patients in China showed that 25% had abnormal lung function after 3 months, and that 16% were still fatigued.”
• Studies are in progress. A number of studies are in progress to follow COVID cases over time to understand long-term effects, some of which we described in our Q&A of 6/11 #Recovery.
• We’ve talked about #Recovery in previous posts, which have some useful information (see Q&A of 6/11, Q&A of 4/30, and Q&A of 3/18 #Recovery).

Figure 1. Recovery Takes Time (from CDC)

Q&A for 10/2:

#CFR #Case fatality rate #Age-specific

Note: I will be traveling this Saturday and Sunday, so no Q&A. Keep sending your questions and I’ll be back at it again on Monday!

Question: What is the death rate by age in the United States?

Answer: Figure 1 and Table 1 show the cumulative case fatality rate (CFR) in the United States by age based on CDC data on cases by age and deaths by age. What I’m presenting below is cumulative (e.g. since the pandemic began) and we know that CFR has declined over time, so the rates in the below table/chart are higher than what the current CFR estimate would be. Still, they show the enormous age gradient. Some of this gradient could very well be based on which age groups are most likely to get tested. For example, one might suspect that most people ages 85+ are likely to get tested if they have symptoms whereas someone in their 30s may be more likely to be tested on a regular basis as part of their work or as a check-up. I bring this up to say that while CFR differences by age are a reflection of greater mortality risk among older Americans, they are also a reflection of who is getting tested. If only sick people get tested, CFR will become inflated — sick people are more likely to have more severe outcomes, like death. If you’re interested in comparing these numbers with totals from other countries, check out ourworldindata. This article in Nature also gives a nice overview, and this article from the Center for Evidence-Based Medicine shows how age-specific CFR has greatly declined over time in Germany.

Figure 1. Cumulative Age-specific CFR in the USA

Table 1. Cumulative age-specific case fatality rates (ratios) in the United States

Q&A for 10/1:

#TN

Question: May I ask for TN charts/maps? Thanks.

Answer: Since we’re headed down to Tennessee this weekend, your question aligned with my curiosity. Here’s the same set of charts that I shared for VA, NYS, and DC earlier in the week, but this time for Tennessee. I made the charts with data from covidtracking.com. You can find data for each state and some nice visualizations on covidtracking.com if you’re ever curious (same goes for you readers who live in other states and want to see trends!). For Tennessee, you can find more local (county) data from the TN Department of Health, here. As to the charts below, what you’ll see is that things are not looking so good in Tennessee. Testing has plateaued with test positivity still above 5%. Cases have plateaued with a recent 7-day rolling average of 1,347 cases/day. The number of people currently hospitalized has been slowly declining, but the decline has tapered in the last week, with a 7-day rolling average of 864 people currently hospitalized. And average daily deaths have been slowly increasing with the current 7-day rolling average of 26 deaths/day. Tennessee needs to increase testing to find more cases, isolate them, and curb community-transmission if it’s going to get a handle on the virus.

Figure 1. Tennessee Cases, Hospitalizations, Deaths

Q&A for 9/30:

#School Safety

Question: Despite our protest, our superintendent [in Texas] is requiring teachers to report to school next week. What steps can I take to protect students and myself?

Answer: I’m sorry that teachers are being forced to do something they have protested. We talked about school reopening and risk a bit in previous posts, including Q&A of 7/28 #Private School and Q&A of 7/27 #School Reopening, and of course there’s more to be said. Two weeks ago, CDC released its “Indicators for Dynamic School Decision-Making,” which are aimed to help schools and communities plan and respond to COVID-19 (Table 1). As you’ll see, the key mitigation strategies for school reopening are those we’re already aware of (bullets are CDC’s suggestions; sub-bullets are my additional suggestions, most of which align with other CDC guidance). As much as possible, just have kids remember these key things: 1) Wear a Mask, 2) Keep your Distance, 3) Wash your Hands, and 4) Outside Gatherings are Safer than Inside Gatherings.

• Consistent mask wearing
• As possible, get N95 masks for yourself. They are even more effective than cloth masks. And if not possible, your cloth mask is still good!
• Consider keeping additional disposable masks on hand to provide to students if their own masks are ill-fitting or get gunky.
• Social distancing
• Keep desks 6+ feet apart.
• Keep students in small pods.
• Avoid large gatherings (like eating in the cafeteria).
• Stagger arrivals/departures.
• Have class outside as much as possible!
• Hand hygiene
• Make time for frequent hand washing.
• Keep hand sanitizer available for students to use.
• Teach students 20-second songs and the like to ensure that they spend enough time washing their hands.
• Remind kids to keep their hands out of their mouths. (no nail biting!)
• Cleaning and disinfection
• Keep disinfecting wipes in the classroom.
• Wipe down high-use surfaces regularly.
• Use gloves to wipe down high-use surfaces.
• Contact tracing
• Ask students and their parents to participate in contact tracing efforts.
• If available, ask students/parents/school personnel to use the Exposure Notification App (as discussed in Q&A of 9/22 #Apps)
• Students must stay home if they are sick!
• Please ask students/parents/school personnel to get tested if they are feeling unwell or have been around a COVID positive person so that contact tracing and be enacted.
• Madeleine’s additional suggestions (do not fit in above buckets)
• Since so much risk depends on local transmission trends, keep up with local transmission trends and consider integrating it into lessons. For state-trends, you can use covidtracking.com or this data visualization tool from Johns Hopkins or this rate of transmission (R0) estimate. For county-level data/trends, you can use data from the Texas Department of Health or from your county health department (probably most relevant).
• HHS is rolling out point-of-use covid rapid testing (discussed in Q&A of 9/16 #Antigen Tests). Talk with your school nurse about getting point-of-care rapid tests for your school.
• Remind kids not to yell or shout as it can propel the virus further (in case anyone is asymptomatic/pre-symptomatic).
• Keep windows open as much as possible and try to ensure that your classroom gets as much fresh air as possible.

Table 1. Indicators for School Reopening (from CDC)

Q&A for 9/29:

#Virgina #VA

Question: I really like the charts you shared on case/hospitalization/death trends in the USA and NYS the other day. Would you please do them for Virginia?

Answer: Sure thing! Please see Figure 1 below and know that you can always find updated Virginia information at covidtracking.com and the Virginia Department of Health. As Figure 1 shows, Virginia is on the right path (and still early into that right path after a long period of plateau at a relatively high level of transmission):

• Testing has again been increasing after plateauing in August and declining for the first half of September (we like to see testing increase!)
• Test positivity rate (rolling 7-day average) has been declining since mid-September and got below the 5% threshold on 24 September. At 4.2%, it’s currently the lowest it has ever been
• Cases have finally been on the decline since having virtually plateaued from mid-July through mid-September. 7-day rolling average of cases (779) is the lowest it’s been since 13 July.
• Hospitalizations have been slowly declining since their most recent peak in early August.
• Deaths have recently increased (7-day rolling average of 22/day). There does seem to be a reporting “fix” on 15 September that created a big bump, but deaths since then have also been higher than recent months.
• Case fatality rate has hovered slightly above 2% (currently 2.2%) since mid-August.

Figure 1. Virginia

Q&A for 9/27:

#Age-specific Case Fatality

Question: Back to Saturday’s Q&A, can you break down the August case fatality rate (1.6%) by age?

Answer: Alas, the covidtracking.com data I used to do that simple analysis does not include age data for cases or deaths, so I cannot run that analysis. I’d need to use a different dataset (and am with a couple of colleagues/friends also looking at race; will show you the analysis when it’s ready; in the meantime, I can tell you that our preliminary analyses show that case fatality rates are declining for every age group). We also know that COVID deaths are highly skewed towards older ages and that the risk of death increases with age, as discussed in many previous Q&As. To elaborate on that point, CDC offers several tables here and here you can check out, and I’ve copied one of CDC’s visualizations herein for ease of reference.

Figure 1. COVID-19 Hospitalization and Death by Age (from CDC)

Q&A for 9/27:

#Communication #Divides

Question: Do you believe fear and perception have played any role in people’s reaction to news about COVID? Both for anti-maskers and pro-maskers and everyone in between? How much role do you think fear and perception plays into people’s reactions to crisis? Whose job is it to think about those reactions, health data professionals or politicians?

Answer: I think there are many aspects of knowledge, attitudes, beliefs, and practices that play a role in how people — all people — are reacting to COVID, including fear. I think that here in the US, health experts and politicians have done a poor job of communicating risk, harm reduction, and the evolution of what we know. I also believe that we all have a role to play in health communication, and loads of present-day factors have made the work all the more difficult. Earlier this week, the New England Journal of Medicine published an article that tackles these issues so thoughtfully, “Tribal Truce — How Can We Bridge the Partisan Divide and Conquer Covid?” I highly recommend reading it. Here are a few of the key points, but again, please read the article — it’s so fascinating and well written and thoughtful. What I’ve included below is less than a shadow of the piece itself.

• Main point: “..communication strategies that bridge our partisan divide over science may prove as important as any novel therapeutic.” Communication/cultural challenges include:
• Absence of consistent communication from nonpartisan experts largely as a result of the sidelining, marginalization, and active underming of such experts by the administration. “The sidelining of all nonpartisan technical experts…has made it very hard for anyone to know what they should do.”
• Increasing distrust of science, especially among conservatives and most prominently among those highly educated conservatives — “greater scientific literacy enabled people to find the limitations in the data or to exploit inevitable uncertainties
• Growing strain of anti-intellectualism, “a generalized distrust of experts that is resistant to facts, though relatively independent of political ideology…. The pandemic, with its myriad uncertainties, well-publicized retractions and shifting recommendations, has most likely exacerbated this distrust. “
• Fusion of beliefs with personal identity (affective polarization). “Rejecting science has become a proxy for personal empowerment and autonomy… “Some people would rather die than wear a mask,” he said. “Once beliefs become fused to your sense of personal identity, they become very difficult to shake.”
• Amplification of conflict through social media. “…[O]ur current political divides are characterized not only by disagreement with the opposing party’s views, but also by frank contempt for the people espousing those views… Social media platforms, rather than facilitating exchanges of viewpoints, tend to thrive on these divisions and make reasoned debate impossible.”
• Exacerbating alienation. “ the pandemic may have further alienated the many Americans who already felt that the “expert” or “elite” class didn’t understand their lives…. What’s it like, he wonders, to be one of these 36 million jobless Americans and to turn on your TV only to hear “the medical experts, technocrats, journalists explain that we must keep the economy closed”? These experts who’ve advocated shutdowns, Zakaria points out, not only have jobs but have been in greater demand because of the pandemic. Emphasizing how worthless and scared the newly jobless might feel, he asks, “Is it so hard to understand why people like this might be skeptical of the experts?””
• Futility of shame for behavior change. “..although disgust is a natural response to blatant disregard for others’ well-being, the collective nature of the consequences doesn’t make contempt any more likely to inspire the behavioral changes we seek…. shaming may better serve our own reputations than the collective welfare.”
• Lack of empathy and harm reduction approaches to COVID messaging. “ …much Covid messaging has “failed to recognize how unrealistic it is to expect people to abstain from the pleasures of life.” Successful harm reduction, says Marcus, requires accepting some level of risk.”

Q&A for 9/26:

#Case Fatality Rates #Trends

Question: If you remove March and April from the death counts/percentages, can you please tell us the rate of death in America? Doctors and hospitals have learned a lot about how to prevent death since the early days of COVID infections and so it would be interesting to know what someone’s chance of death would be in today’s healthcare system vs early in infections.

Answer: Case fatality rates have been declining over time in the United States, which is fantastic news! Part of this decline is due to demographic shifts in the cases — especially changing age distribution of cases. With more and more cases among young people who are less likely to have severe outcomes, we’d expect to see a declining case fatality rate. Part of the decline is also due to increases in testing, which allow us to capture more mild and moderate cases than ever before. And part of the decline is surely due to improvements in treatment, enhanced provider experience, and health systems resilience (as discussed in previous Q&As, most recently Q&A of 7/30 #Mortality). I’ve got a side project going with a couple of colleagues on case fatality trends and hopefully I can share more on this in the coming days! In the meantime, I ran a very simple (overly simple) analysis of monthly case fatality rates using data from covidtracking.com (Table 1).

As you can see, in March we were not widely testing and most all cases identified were serious cases that resulted in hospitalizations and oftentimes death. Because of so much missing case data, the case fatality rate in March is nowhere close to “real”. As the months have progressed, case fatality rates have fallen even as the monthly number of deaths has increased. Note: because deaths lag cases, I compared monthly deaths to mid-month cases — ex: deaths in August are cumulative from August 1–31 while cases in August are cumulative from July 16-August 15.

Table 1. Case Fatality Rates Have Declined Each Month in the United States

Q&A for 9/25:

#USA #NYS #DC

Question: About a month has passed since we last looked at COVID case/hospitalization/death trends. What’s the update?

Answer: Yep, we last talked trends in our Q&A of 8/30 #USA. Below are charts for USA, NYS, and DC that I made using data from covidtracking.com. My friend, Dr. YJ Choi, just updated her Maryland charts and if you want a deep dive, please take a look!

Figure 1. USA: It’s a mixed bag, but still mostly bad. On the plus side, daily tests are on the rise and the daily number hospitalized is the lowest it’s been since late-June. On the negative side, cases are on the rise, the percentage of tests that is positive is still above 5%, and the 7-day rolling average of daily deaths has plateaued for the last two weeks.

Figure 2. NYS: Still looking good, especially with the increase in testing and very low test positivity rate. Go New York! One trend to be keep a watchful eye on — daily cases and hospitalizations have both slightly increased. We’d expect cases to increase because of increased testing, but that wouldn’t account for the slight increase in hospitalizations. A slight increase in hospitalizations would indicate a slight uptick in spread.

Figure 3. DC: Also looking good! Tests have increased while test positivity and daily cases have both decreased! Hospitalizations remain plateaued, but deaths are increasingly infrequent.

Figure 1. USA

Figure 2. NYS

Figure 3. DC

Q&A for 9/24:

#Farts #Gas #Analogy

Question: I thought of an analogy today and I wonder what you think of it. If I fart indoors and I’m 6 ft away from someone, they will still smell it. If I fart outdoors and I am 6 ft away, they likely won’t. Could this be a helpful way to explain the dissipating effects of being outdoors as well as the risks indoors? Heck, I wouldn’t fart indoors even if I was 20 feet away, but I might risk farting outdoors (depending on the breeze of course) even if I was 3 feet away. The same thing can be said for COVID. (and a mask will, of course, help in any of the situations)

Answer: Your analogy made me laugh, thanks! And if people are confused about why outdoors is safer than indoors then I think your analogy is great! There are two questions that may arise in making this analogy though, and I raise the questions and answers because the internet raised them earlier in the pandemic:

1. If you can still smell a fart through your mask, what good is the mask doing for you?: As Trevor Makal, chemistry professor at University of Virginia explains that farts smell because they contain methanethiol, which is about 0.4nanometers (nm) in diameter. Meanwhile, most viruses range from about 20 to 400 nm — and SARS-CoV-2 is 60 to 140 nm in size. “The difference in sizes of the COVID-19 virus and a common odorant in farts is 2–3 orders of magnitude (100–1000 times the diameter of the smaller methanethiol).” Most tight weave masks will block the virus, but because the odor molecule of a fart is so much smaller, the smell gets through. Masks== protect from virus, not from stink.
2. Can coronavirus be spread through farts?: No! Snopes did a factcheck on this one after online rumors were apparently flying and even Stephen Colbert did a bit (around minute 5:22). Basically, pants and other clothing keep the aerosol components of farts contained; it’s these aerosol components that carry wee bits of feces with them, which are the only components of farts that could be linked to disease; there’s evidence that the coronavirus can be found in feces, but as CDC writes, “it is unclear whether the virus found in feces may be capable of causing COVID-19. There has not been any confirmed report of the virus spreading from feces to a person.” Basically, as long as you wear pants when you fart and/or stay far away from other people when you fart, you will not spread any disease, including coronavirus. You’ll just spread some stink!

Q&A for 9/23:

#Sports

Question: Earlier in the summer, a number of Covid Risk Assessment Charts made the rounds, such as this one: https://www.businessinsider.com/how-to-decide-when-to-go-out-during-coronavirus-pandemic-2020-7 I’ve not seen any charts like these recently in general or new charts with updated information. I have been noticing many of the high risk activities (according to the various risk assessment charts) are now widely happening. In particular, team sports for both children and adults appear to be happening, and the start of the academic year seems to be a major factor. Have any of the risks associated with any of these activities changed, or is it that our society has decided these activities outweigh the risks?

Answer: I think people’s behavior has changed over the months for various reasons — risk perceptions have changed, risk/benefit calculations have changed, people have a more nuanced perception of risk, and some people are tired of minimizing risks. Some of the change is evidence-informed and some of it is just human behavior. Turning to sports, if you were looking for a yes/no or do/don’t answer, you’re unlikely to get it. On 18 September, the American Academy of Pediatrics (AAP) updated its clinical guidance on return to sports for children and adolescents. And CDC offers sports recommendations for youth and adults, as well as this colorful risk diagram (Figure 1) and helpful video. The upshot of all this guidance is== make your own determination based on your/your child’s circumstances and try to minimize as much risk as you can. Here are a few excerpts from AAP guidance:

• “Ultimately, the decision falls on parents/guardians to decide whether they will allow their children to participate in sports.”
• “Because prolonged, close contact with a person infected with SARS-CoV-2 is the main driver of transmission, the sport (number of players, spacing, and frequency and duration of contact) and setting (indoor versus outdoor, size and ventilation of facility) will likely influence risk of infection. Although it is not likely the main form of transmission, it is possible for SARS-CoV-2 to be transmitted on surfaces; therefore, sports with shared equipment, facilities, or common surfaces may pose additional risk.”
• “Weighing the risk versus benefit of return to sport is driven by the sport and setting, local disease activity, and individual circumstances, including underlying health conditions that place the athlete or household contacts at high risk of severe disease should they contract SARS-CoV-2 infection.”
• “Risk can be decreased but not eliminated by athletes, parents, coaches, and officials following safety protocols.” [Note: CDC and AAP offer many pieces of guidance for reducing risk for those who choose to play/coach/spectate.]

Figure 1. Low Risk to High Risk Continuum of Sports Competition (from CDC)

Q&A for 9/22:

#Exposure Notifications #Apps

Question: Have you turned on exposure notifications on your iPhone? Do you recommend doing so? If your region has an exposure notification app it directs you to download that state/regions app. Apps are currently available for a limited number of states, to include Virginia. Do you recommend downloading and using it?

Answer: Thanks to your question, I realized I had the option to turn exposure notifications on! (Clearly, I have not been paying attention to my iOS updates.) Anyway, after doing some reading, I did just attempt to turn the exposure notifications on. But… I live in Maryland and the state public health officials have not yet turned on exposure alerts. I can’t use the system yet, but that should soon change. Based on the news, it sounds like Maryland and DC are both soon (early October perhaps) deploying the “Exposure Notification Express” system. Upshot is — I do recommend downloading and using exposure notifications, including Covidwise if you live in VA (Figure 1).

I’ll elaborate a bit more in the bullets that follow, and if you’re interested in reading more, I found these articles from the Washington Post, Slate, and Vox especially helpful in coming to this recommendation. The exposure notification system:

• Was developed/built through an Apple/Google partnership and was first rolled out as an API that app developers could use to develop their own apps. In early September, Apple/Google modified the system so that state public health officials could use it off-the-shelf, thereby simplifying the process and minimizing additional cost outlays.
• Uses bluetooth signals to recognize whether you may have been exposed to coronavirus in the last 14 days (e.g. been in prolonged (15+ minutes) close contact with someone who tests positive)
• Does not spy on you. It does not collect any user data, even location data, except for 14-days worth of bluetooth beeps.
• Works like this: Basically, anytime your phone comes close to another phone using an iOS/Android operating system, it emits a series of bluetooth beeps that are random, but special to your phone. The app stores these beeps for 14 days. If a person you’ve met with over the last 14 days tests positive, the health department will give them a 6-digit code to enter into the app. The app then uses all the stored beeps to send out an alert to every phone that was in close proximity for 15+ minutes in the previous 14 days. No other information is shared. It’s basically a nudge to go get tested.

Since there’s no real privacy risk and a good benefit of receiving a nudge to get tested, it overall seems like a good thing to have and use. Plus the more of us who have and use it, the more helpful the app will be. As of 14 September, Virginia’s Covidwise app has been downloaded 515,824 times, with an estimated 12% of Virginians between the ages of 18 and 65 having downloaded it;155 Virginians have used the app to anonymously submit their positive test results.

Figure 1. Virginia’s Covidwise App

Q&A for 9/21:

#Fear #Deaths #Response

Question: Fascinating piece about the data. You’re a data person, what do you think?

Answer: You’ve shared a Medium piece written by an investment banker whose premise is that “Today we live in a nation where nearly half of all U.S. citizens deeply believe they will get the Covid virus and die. This fear is pervasive, and it is false.” If I understand his argument correctly, the idea is that: because of America’s media and social media platforms, we are a nation in fear; our fear has caused us to over-react; in our fearful overreaction, we have destroyed our economy; what we need is dispassionate review of the death data, which shows that we really shouldn’t be all that worried; and we should therefore stop lock-down or any phase thereof (ex: open indoor dining) to save our economy.

Personally, I disagree with this author’s premise and conclusions. First, even if your own personal risk of severe COVID outcomes (including death) is low, it doesn’t mean that the risk is low for everyone! Our country already has >200,000 excess deaths this year (see Q&A of 8/28 #Excess Mortality). Second, most of us fear that someone we love will be hit hard by COVID. In fact, half of Americans know someone who has been infected with COVID and 20% know someone who has died of COVID. Third, the idea of choosing one or the other — either health or economy — is a false dichotomy. If we can get the virus under control, we can fully reopen the economy (other cities/countries have done it, we can too!). We also know that if we try to fully open before we get the virus under control then we can expect to see cases rebound and deaths increase (as discussed in many previous posts, including more recently in Q&A of 9/10 and Q&A of 9/3). Finally, I’m highly skeptical of any broad-brush blaming of “the media.” Where’s the data showing that the media has caused an over-reaction? Here are a few more thoughts (note: I could write even more but am reeling it in!):

• Author’s Statement: “With the advent of 24-hour cable and social media news feeds, the infection and death count rolls on from 50,000 deaths to 150,000 and soon 200,000 — harrowing statistics bombarding Americans and inducing and reinforcing fear…”
• Response: The author does not present any data on the influence of “the media” and stoking COVID fear. Yes, we have many issues with American media, but making sweeping statements to support your given point of view is not evidence-informed or helpful. It’s also an unfair portrait of Americans. Axios-Ipsos polling found that as of early August, 50% of Americans know someone who has contracted COVID and 20% of Americans know someone who has died of COVID. As of late-June a Washington-Ipsos poll found that 31% of Black Americans report knowing someone who has died of COVID. Blaming media for fear when so many of us have direct experience discounts our lived reality.
• Author’s Statement: “Nearly half of all U.S. citizens deeply believe they will get the Covid virus and die.”
• Response: I have not seen any data point that aligns with this statement. Even the statistics the author shares in his post do not directly support his statement — “Polling by Gallup indicates approximately 45% of Americans are “very worried” or “Somewhat worried,” they will contract Covid. Pew Research reveals 51% of adults having “high” or “medium” psychological distress from their fear of Covid. The American Psychiatric Association’s research indicates that 40% of Americans believe they could become seriously ill and die from Covid.” Being worried, having some distress, and believing that you could become seriously ill and die from COVID are not equivalent to believing you will become seriously ill and die. The author cites American Psychiatric Association’s research, which also found that “far more Americans (62%) are anxious about the possibility of family and loved ones getting coronavirus.” If we want to talk about fear, this is the fear we should talk about.
• Author’s Statement: “We call this the ‘Data-Fear Gap,’ and it is reinforced by a relentless media barrage supporting fear-based policy reactions having far-reaching and long-lasting consequences more deadly than the virus itself on both people and our economy.”
• Response: The author does not describe in detail what “fear-based policy reactions” he is referring to, but he does mention earlier in the post that “Calls are loud to test universally, lockdown every business, close colleges, stadiums, and arenas, mandate masks even outdoors, and undertake a new Manhattan Project to find the vaccine.” Aside from locking down every business (which is hyperbole), I’d argue that the other policy reactions are evidence-based. We know that the virus more easily spreads in high congregant settings, including arenas and stadiums. We know that masks are highly protective, and we also want to support mask wearing broadly so it becomes the social norm.
• Author’s Statement: “The empty storefronts in New York, Boston, Chicago, San Francisco, and an increasing number of major cities will remain vacant until irrational fear is replaced with commerce.”
• Response: It’s not the fear that has destroyed our economy. It’s our ineffective response to the virus. If we can get the virus contained so that we stop community transmission, we can reopen the economy. This has been done elsewhere and it can be done here!
• Author’s Statement: “Data on who is infected, who becomes ill, and who has died from Covid isn’t subject to many questions; it is objective, available and knowable data.”
• Response: I wish data were this available and knowable. Even now we still don’t have race data for half of cases. We’re still having issues with hospitalization data completeness, making statistics like hospitalization rate more challenging to reliably compute. Another wrinkle here is that because we’re dealing with a new virus, we don’t know its long-term impacts. There is much that is still unknown, and much more work to be done to ensure data availability and completeness. Important caveat — the US does have a strong civil and vital registration system (see Q&A of 5/5 #Counting Deaths).
• Author’s Statement: “Until the 40% of Americans who currently believe Covid19 will kill them become informed that this is an exceedingly remote risk (again, the math is .01%), there will be a very tepid American recovery. The misery and deaths from that Data-Fear Gap are owned by America’s media and social media platforms, which could be a far more deadly affliction than the Coronavirus itself.”
• Response: Disagree with this premise and the “risk” math is overly simplistic and incorrect. The number of COVID deaths we experience will be proportional to our actions. There’s no “set number.” Just as there is no set “risk” — it depends on your own underlying health + your exposure + the healthcare you’re provided with. That said, as discussed in previous posts (more recently in Q&A of 9/17 #Children) it’s important to remember that deaths among young people are rare. Additionally, the current case fatality rate in the U.S. is on the decline at 2.9% (calculated using data from covidtracking.com).

Q&A for 9/20:

#Caregiving #Home

Question: Fingers stay crossed that neither me nor my husband come down with the virus. Planning ahead though…..if that happens, how does one care for the other in a small apartment with one bath? It’s possible to sleep apart, but total separation would be difficult. And, if our son gets it (he’s two hours away, lives alone), would it be prudent to bring him to our house where he can isolate in the basement but not be alone? Am I over-reacting? As always, thanks!

Answer: So many people are facing these questions! While I’m not nearly the planner you are, it does make me feel better to have a plan and to at least feel as though I have some agency. Fingers crossed, masks worn, and distance kept — you and yours stay healthy — but just in case, here’s the scoop, synthesized from CDC guidelines and for a more entertaining take, please check out this short video from Yale School of Medicine (Figure 1):

1. Help with basic needs. Provide food, drink, medicine, etc. (all from a distance)
2. Watch for warning signs. Have the doctor’s number handy and reach out if you have questions or concerns. Call 911 if you see emergency signs — trouble breathing, pain or pressure in the chest, confusion, inability to stay awake or to sleep, or blue lips/face.
3. Protect yourself.

• Keep physical distance. Be kind to your family member and emotionally supportive, but try to keep at least 6 feet away. This means sleeping in different areas, eating in different areas, leaving food and drink beside a person (or at their room’s door), keeping separate bedrooms and bathrooms (if possible) etc.
• Wear masks. When you are engaging with your family member, both of you should wear face masks.
• Keep airflow. If you have to share space, including a bathroom, keep a window open and fresh air circulating.
• Clean and disinfect. Frequently disinfect high touch surfaces. Use hot water and soap to wash dishes. Use gloves to wash dishes, clean bathrooms, do the laundry, and clean up after your sick family member as needed. Use trash can liners.
• Avoid sharing personal items. Use different dishes, towels and the like.
• Track your own health. Keep track of how you’re feeling and reach out to your healthcare provider.

4. Protect others.

• Self quarantine. Stay home for 14 days after your last exposure. This seems really challenging since the person who tests positive/is sick, is supposed to stay away from others for at least 10 days since the positive test (for asymptomatic folks) OR (for symptomatic folks) at least 10 days since symptoms first appeared + 24 hours since last fever + other symptoms are improving. If you’re the household caregiver, this means that you need to consider the last exposure to be the 10th day since your family member’s positive test/symptoms and then add 14 days.
• No visitors. Please ask for help from others, but please do not have them into your home.
• If you have to leave. Keep your distance, wear your mask, wash your hands, and avoid any interactions that could last >10–15 minutes and possibly expose others.

When it comes to taking care of your son, since he’s the youthful one and you and your husband are at greater risk of more severe outcomes, I think it’s best if you keep your distance. Personally, I wouldn’t recommend inviting him to stay in your home (even if it is your basement). Instead, I’d recommend having regular/frequent check-ins, sending food, getting your son’s healthcare provider information (just in case), etc.

Figure 1. Keep physical distance (screenshot from Yale video)

Q&A for 9/19:

#Eyes #Eyeglasses

Question: I thought this headline was a joke, “Does Wearing Glasses Protect You From Coronavirus?” Is there anything to it?

Answer: Ha! I was just reading that study, which was published in JAMA Ophthalmology earlier this week. Basically, the study authors were curious to know whether they could find an association between wearing eyeglasses (at least 8 hours/day) and COVID-19 infection risk, with the hypothesis being that because the eye may be an important route of COVID infection, people who wear glasses may have less exposure to the virus, and therefore less COVID-19 disease incidence. To test their hypothesis, study authors took a look at data from a group of 271 hospitalized patients in Suizhou, China and compared the proportion of eyeglass wearers among those hospitalized with the proportion of eyeglass wearers in the local population. As it turns out, the proportion of eyeglass wearers among those hospitalized was much lower than the general population. Study authors were quick not to draw conclusions about any causal relationship — and rightly so (this study is WEAK!) — instead focusing their conclusions on the need to pay more attention to the possible role of the eye in COVID-19 infection and prevention. I’m down with that conclusion, so in that respect there’s a bit of a “there there” to this study.

That said, I was also a bit surprised that this research brief was published since it is some very weak science. Perhaps the editorial board was ginger about it too, publishing alongside the study an invited commentary that dives further into the study’s limitations, concluding “The study by Zeng et al is provocative and raises the possibility that use of eye protection by the general public might offer some degree of protection from COVID-19. More retrospective and prospective studies are needed to confirm the association that was observed in this study and to determine whether there is any incremental benefit to wearing eyeglasses or other forms of eye protection in public settings, in addition to wearing a mask and physical distancing, to reduce the risk of acquiring SARS-CoV-2.” [Note: For more on COVID and eyes, see Q&A of 7/19 #Face Shields and Q&A of 4/4 #Eyeglasses]

Q&A for 9/18:

#Antigen Tests #False Positive #Widespread Testing

Question: Reflecting back on the Q&A of 9/16, I thought I remembered the governor of Ohio getting a false positive when he was set to greet the president at the airport. He then got tested two more times and tested negative, and he gave people a heads up about the rapid tests not being accurate. That being said, does it make sense to go once a week to get a rapid test? Or is it just a waste of time and resources?

Answer: Your memory is spot on. No test is perfect, and the likelihood of an antigen test giving a false positive depends on the prevalence of infection among the testing population. Personally, I support frequent, widespread use of the antigen tests AND I want to remind us all that we cannot rely on testing only. A negative test result does not give license to forgo other key public health measures, like social distancing, mask wearing, hand washing and the like. Read on for more detail and data!

The Abbott test we discussed in our Q&A of 9/16 #Antigen Tests, reportedly has a “sensitivity of 97.1% (positive percent agreement) and specificity of 98.5% (negative percent agreement) in patients suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.” As Table 1 shows, as overall prevalence increases, the possibility of false positives declines and the possibility of false negative increases. And as Figure 1 shows, antigen tests are only strong at identifying true positives when viral load is at its peak, relatively early on in infection. For these reasons, it’s especially important to work with your health provider to determine if you need another test (i.e. a PCR test) after having an antigen test, especially if you are asymptomatic and receive a positive antigen result or symptomatic and receive a negative antigen result.

When it comes to how frequently to test, a couple of days ago, Nature published a good overview, “Fast coronavirus tests: what they can and can’t do.” As described in the article, a couple of new pieces of research have shown the benefit of widespread rapid testing conducted frequently (even as often as 2x/week) to curb the spread of the epidemic. There’s no guidance (to my knowledge) on widespread population-based testing. Meanwhile, CDC suggests, “Rapid antigen tests can be used for screening testing in high-risk congregate settings in which repeat testing could quickly identify persons with a SARS-CoV-2 infection to inform infection prevention and control measures, thus preventing transmission.” CDC also offers guidelines for antigen testing in nursing homes. Others are pushing use of antigen testing to curb transmission in colleges and HHS recently suggested using antigen testing for use in schools (for more on #Universal Testing and schools, see Q&A of 9/1). While many folks have reservations about antigen tests in various scenarios (for more, see Nature article referenced above), public health experts agree that more widespread testing is absolutely necessary to curb the spread of the virus.

Table 1. Abbott Antigen Sensitivity/Specificity in Different Scenarios

Figure 1. Probability of Positive Result by Test Type (from Nature)

Q&A for 9/17:

#Infants #Children #Underlying Conditions #Heart

Question: My daughter was born in March and immediately diagnosed with a congenital heart defect. She has already had 2 open heart surgeries and needs another next month. She also has a feeding tube. If you haven’t already done one, could you do a daily Q&A on considerations for babies/ kids with underlying health conditions? Thanks!

Answer: You and your baby girl have been through such a challenging time these last six months. My hat’s off to you both. I’ve done several Q&As on COVID and kids (most recently Q&A of 9/2 #Kids and Q&A of 7/24 #Children), but there’s more data now and I don’t believe we’ve talked specifically about kids with underlying conditions. In short, while underlying conditions put infants/children at greater risk of severe COVID-19 outcomes, the risks are still very small.

• The good news is that severe COVID-19 outcomes among children are very rare. The COVKID Project tracks COVID-19 cases, hospitalizations, and deaths among children across the country. As of 14 September, among children and teens there were nearly 3.2 million total cases, 1,332 pediatric intensive care admissions, and 130 total deaths.
• The not so good news is that children with underlying medical conditions might be at increased risk of severe illness, and severe illness disproportionately affects Black, Hispanic, and American Indian children. Two days ago, CDC published a new report on COVID-19 deaths in children nationally, “SARS-CoV-2–Associated Deaths Among Persons Aged <21 Years — United States, February 12–July 31, 2020.” The report examined the demographic characteristics and underlying conditions of those who died. Of the 121 reported deaths as of 31 July, 75% (91) had 1 or more underlying medical conditions. Of all reported deaths, 78% (91) were among Black, Hispanic, and American Indian children. Focusing again more specifically on your circumstances, only 10% (12) of deaths were among infants, and of all 121 reported deaths only 2% (3) had congenital heart disease. So even among infants and children at greater risk, the risk is still very low but clearly not insignificant.
• Turning to pediatric congenital heart disease more specifically — another study out of Europe published in Lancet on pediatric COVID-19 found that of the entire cohort studied (585 children with COVID-19), 4% (25) had congenital heart disease, of whom only 5 needed intensive care. For more on pediatric congenital heart disease considerations, this article from several months ago published in the Journal of the American Heart Association and describes some of the potential vulnerabilities among pediatric patients and this article from June as well as this one from August published by the American Society of Echocardiography provide some specific guidelines for providers assisting pediatric congenital heart disease patients.

Q&A for 9/16:

#Antigen Tests #Rapid Tests

Question: I just got a text from an urgent care provider saying they are now offering “FDA authorized Covid-19 Rapid Testing, results in 15–20 minutes!” I’ve read previously that rapid tests can give a significant number of false positives and false negatives. Do you have current information to provide on this, and also any guidance on whether or not the rapid tests are useful even if not always accurate?

Answer: I think the test your urgent care provider is referring to is the new Abbott BinaxNow antigen test, which received FDA emergency use authorization in late August. We discussed different test types most recently in our Q&A of 9/4 #Test Types, and the table shared in that post provides an overview of the three test types — molecular (e.g. PCR), antigen, and antibody. Overall, antigen tests are a great addition to our testing menu because they:

• Are inexpensive (ex: Abbott is selling its new test for $5)
• Are simple for healthcare workers to use (ex: the Abbott test is the size of a credit card and requires no additional equipment like an analyzer)
• Provide results quickly (ex: new Abbott test provides results in 15 minutes)
• Are designed to detect active SARS-CoV-2 infection

In short, these new antigen tests allow us to make COVID-19 testing more widely available, with results provided more quickly than traditional molecular/PCR testing (yay!).

But it’s not all sunshine — you’re right to remember that different tests also have drawbacks. For antigen testing, positive results are generally very accurate (e.g. if the test tells you you’re positive, you’re really positive), but negative results are not as accurate (e.g. a negative antigen test cannot rule out active infection). Re-stated, with antigen tests, you’re unlikely to get a false positive, but there’s some chance of a false negative (and for a refresh on sensitivity/specificity see Q&A of 4/15 #Sensitivity). So if you and/or your healthcare provider believe that you may be infected with SARS-CoV-2 and an antigen test comes back negative, you’ll need to have a molecular/PCR test too.

Q&A for 9/15:

#Halloween #Dos and Don’ts

Question: What do you think about Halloween festivities this year, particularly trick or treating?

Answer: I love Halloween and I think as long as we implement a few additional safety measures, there are elements of it that we can keep doing, including trick or treating. First, let’s remember the current dos and don’ts of the strange times we’re living in (Table 1). Based on the “DO NOT” list, we should NOT be: hosting Halloween parties, visiting “haunted houses,” taking “haunted hay rides” or the like, bobbing for apples, joining parades…. But, based on the “DO” list, we can indeed keep trick-or-treating as long as we follow the “DOs”. What this might look like in practice is:

• Small, family-based trick-or-treater groups (e.g. siblings or parent + child(ren); no friend groups or extended family groups)
• Masks on everyone (and if your costume has a mask, add an appropriate facemask too)
• No jump scares that cause people to scream
• Ideally, no knocking on doors. Candy givers can instead sit on their porch or keep their doors open to greet trick-or-treaters from a distance.
• Ideally, candy should not be passed out, but should instead be located where the children can directly pick up each piece. Lots of examples on the internet abound, like hanging candy from trees or using a candy shoot. We’ll likely just line candy up on the path to our front door and ask kids to take a couple. I suppose we could also throw candy to kids, like we throw mardi gras beads. Be creative!
• Bring hand sanitizer to use as needed.

Table 1. Dos and Don’ts

Q&A for 9/14:

#Restaurants #Risk

Question: So how well done was this study that is garnering headlines? I have reservations. (Couldn’t resist the pun.)

Answer: You’re punny! Hehehehe…. le sigh. Good question too! Three days ago, CDC released results from a small study, “Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults ≥18 Years in 11 Outpatient Health Care Facilities — United States, July 2020.” Two of the study’s findings have made a lot of waves — dining at restaurants and going indoors to bars/coffee shops are both associated with increased odds of COVID infection. As with all studies, this one has strengths and limitations. In my opinion, it’s still too small and too limited to make definitive conclusions, so you’re right to have reservations. That said, we have evidence of transmission events occurring in both indoor restaurant and bar settings (see Q&A of 6/3), and this study adds to the evidence base. In fact, I think it’s the first (or one of the first) studies to look at exposures by outcome, which is a major strength of this study. My main take-away is to keep getting take-away (hahahaha!). Seriously, please keep minimizing risk.

Now a bit more on a few of the study’s limitations — Because this study did not differentiate between indoor/outdoor dining, it’s unclear what the level of risk is for the type of dining. We expect that indoor dining carries higher risk than outdoor dining (see Q&A of 5/20). Second, because the study lumped indoor visits to bars/coffee shops together in the questions asked, and did not differentiate by service delivery method, we cannot know whether the risk identified pertains only to bars, only to coffee shops, to both, and for what type of service delivery method. Furthermore, the number of individuals included in the bars/coffee shops analysis is so small (only 13 cases and 8 controls said yes to the question); really too small to draw conclusions. The same can be said for several other community exposures reported for which no association was found (e.g. gyms, church, public transport) — with so few cases/controls reporting these exposures, the study does not have the power to identify elevated risks. Finally, I wonder whether people who report dining at restaurants and/or going to indoor bars/coffee shops have other behaviors that are more risky and not measured in this study. Perhaps these behaviors are proxies for other risky behaviors — like more comfort/more exposure to sitting for prolonged periods with groups of people in myriad types of settings?

Study Overview

• Study question: Do community and close contact exposures differ by infection status (infected vs uninfected)?
• Methods: Symptomatic adults who recently tested positive for COVID-19 (cases) and symptomatic adults who recently tested negative for COVID-19 (controls) were recruited from 11 health care facility settings across 10 states to participate in the study. Both cases and controls were asked a series of questions about their activities in the 14 days before receiving a COVID-19 test (e.g. their community and close contact exposures). Researchers then compared exposures between cases and controls, adjusting for age, sex, race/ethnicity, and presence of one or more underlying chronic medical conditions.
• Results: Cases were far more likely to have been in close contact with a COVID-19 infected individuals, most of whom were infected family members (42% of cases vs. 14% of controls). For all measured community exposures, only one was statistically significantly higher among all cases — dining at a restaurant. Indeed, restaurant dining was found to be associated with an approximate two to three times increased odds of COVID infection (Figure 1). The study authors state, “case-patients were more likely to have reported dining at a restaurant ([adjusted odds ratio (aOR)] = 2.4, 95% CI = 1.5–3.8) in the 2 weeks before illness onset than were control-participants. Further, when the analysis was restricted to the 225 participants who did not report recent close contact with a person with known COVID-19, case-patients were more likely than were control-participants to have reported dining at a restaurant (aOR = 2.8, 95% CI = 1.9–4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5–10.1).
• Limitations: The study authors list five limitations of their study: 1) The controls may have had similar exposures to the cases since the controls were a group of symptomatic adults who tested negative (e.g. different from the general population), and a number of potential participants did not respond or refused to participate and they may be systematically different from those who agreed to participate; 2) Unmeasured confounding — reported behaviors might represent activities/behaviors not represented/asked about in the study. Especially limiting is that the study did not distinguish between indoor/outdoor dining; 3) Study participants were recruited from 11 health facilities and may not be representative of the broader US population; 4) Participants were aware of their COVID test result, which may have biased their reporting; 5) Case/control status may be misclassified because of imperfect sensitivity/specificity of PCR tests.

Figure 1. Adjusted Odds Ratio for Community Exposures (from CDC)

Q&A for 9/13:

#Flu #Revaccination

Question: So based on yesterday’s post, since I got the shot at the end of August when I knew I was going to be running around NY for work, should I get another shot in say February?

Answer: As you know, I’m not a medical doctor, so please consult your physician. Based on what I’ve read, it appears that revaccination is generally not recommended, but is also not actively discouraged (read more below). If you do choose to explore revaccination, it would probably be better to do it in December since influenza season is generally at its peak in January and February, and it takes about 2 weeks after vaccination for your body to develop protective antibodies.

• No revaccination recommendation. First, the chartered Federal Advisory Committee, Advisory Committee on Immunization Practices (ACIP), makes yearly recommendations on influenza vaccination. Those recommendations that CDC approves become codified as CDC guidelines that are published yearly in a special Morbidity and Mortality Weekly Report (MMWR). This year’s guidelines were published in August and state that “No recommendation is made for revaccination later in the season of persons who have already been fully vaccinated (i.e., providing a booster dose).” I take this to mean that ACIP neither endorses nor discourages revaccination. That’s another solid reason to consult your physician!
• Only one dose is actively recommended for adults. In its immunization FAQ, CDC writes, “Can vaccinating someone twice provide added immunity?: In adults, studies have not shown a benefit from getting more than one dose of vaccine during the same influenza season, even among elderly persons with weakened immune systems. Except for children getting vaccinated for the first time, only one dose of flu vaccine is recommended each season.”

Q&A for 9/12:

#Flu #Vaccination #Timing

Question: I remember hearing that there’s an ideal time to be vaccinated against the flu, and that vaccination too early can be a problem for later in the flu season. Is that true? Is there an ideal time to be vaccinated?

Answer: Thanks for asking, and everyone, please go get your flu vaccination! There is a lack of consensus as to the optimal timing of flu vaccination, but if there is an optimal time, it is right now (September) through the end of October! And you can get vaccinated in so many places — your local drug store, walk-in clinic, grocery store pharmacy, your primary care provider, even many workplaces offer flu shots. Don’t delay, do it today!

Now that you’ve read through my public service announcement, here’s the scoop on the timing question:

• Flu vaccination at any time is better than no vaccination. As CDC states, “everyone ages 6 months and older should get a flu vaccine every [flu] season with rare exceptions.”
• Evidence has been accumulating over the last decade indicating that influenza vaccine effectiveness diminishes more rapidly than anticipated. This means that folks who get vaccinated early (like in July) could be at risk much later in the flu season and at peak flu season (generally January/February). As stated in this year’s Influenza Recommendations published in CDC’s MMWR, “early vaccination (i.e., in July and August) is likely to be associated with suboptimal immunity before the end of the influenza season, particularly among older adults.”
• Some researchers working in this space suggest that the optimal flu vaccination time for most people is September/October.
• On the flip side, as stated in this year’s Influenza Recommendations, “Variable data concerning presence and rate of waning immunity after influenza vaccination, coupled with the unpredictable timing of the influenza season each year, prevent determination of an optimal time to vaccinate.”
• All that said, CDC recommends getting vaccinated before flu viruses begin spreading in your community (Figure 1).
• So again, please go get your flu shot! We want to avoid the double burden of COVID-19 + Influenza and we can help protect ourselves and our community against influenza by getting our yearly vaccination. All our other public health prevention activities — mask wearing, social distancing, hand washing, etc — will also help protect us against influenza, so keep at it!

Figure 1. When should I get vaccinated? (from CDC)

Q&A for 9/11:

#Ibuprofen

Question: Remember when there was commotion about ibuprofen and COVID-19? Any updates?

Answer: Yes, I remember! We talked about the hypothesis that ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) might aggravate COVID-19 infection way back in our Q&A of 3/28 #Ibuprofen. And now there’s a new study on the topic that was published in PLOS/Medicine just three days ago, “Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.” Some good news — study authors found that NSAIDs were NOT associated with any increased risk of death, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy; NSAIDs do not lead to more severe COVID-19 outcomes! Here’s a very brief synthesis of the study:

Study authors used data from the Danish administrative and health registries to identify people who tested positive for SARS-CoV-2 between late-February and late-April. Of the individuals who tested positive, the researchers identified those who were NSAID users (defined as having filled a NSAID prescription in the 30 days before a positive test). Researchers then matched NSAID to up to 4 non-users based on propensity score matching (i.e. matched according to similar characteristics like age, race, sex, other comorbidities, and use of other prescription drugs) to compare outcomes over a follow-up period of 30 days (for death) and 14 days (for all other outcomes listed above, including hospitalization). The authors found, “In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (Relative Risk (RR) 1.02, 95% CI 0.57 to 1.82, p = 0.95; Risk Difference (RD) 0.1%, 95% CI −3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI −3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI −3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI −2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD −0.2%, 95% CI −2.0% to 1.6%, p = 0.81).”

Q&A for 9/10:

#Preventable Deaths #Models

Question: I’ve seen in the news that if the US had responded to COVID-19 just two weeks more quickly, as many as 84% of deaths could have been prevented. Can you explain why that is?

Answer: I think the study you’re referring to, which made waves a few months ago, is this one from three researchers with Columbia University, “Differential Effects of Intervention Timing on COVID-19 Spread in the United States.” I assume that it’s making waves again given the revelations revealed yesterday that the President knew of the severe danger COVID-19 posed at least as early as Feb. 7 when he stated in a call with Bob Woodward that “You just breathe the air and that’s how it’s passed, and so that’s a very tricky one. That’s a very delicate one. It’s also more deadly than even your strenuous flus… This is more deadly. This is 5 percent versus 1 percent and less than 1 percent. This is deadly stuff.” Given that backdrop, I’ll share an overview of the study and discuss how actions (and lack of action) can impact the trajectory of the pandemic.

• Study Overview. This study, published in late-May on a pre-print server, has not been peer-reviewed. The authors used an SEIR (susceptible, exposed, infectious, recovered) model to estimate the impact of the non-pharmaceutical interventions (NPIs, e.g. social distancing; limited population movement) implemented between March 15-May 3rd on rates of transmission, new cases, and deaths. The authors then re-ran the model to examine the impacts on new cases and deaths of earlier applications of NPIs — 1 week earlier and 2 weeks earlier. In doing so, they estimate that had the US adopted NPIs 2 weeks earlier, more than 1 million cases and 58,000 deaths would have been averted. At that time, this would have been equivalent to an 89% reduction in deaths (95% confidence interval: 84%-94%) Note: for overview of models see Q&A of 4/5 and Q&A of 5/4 #Models.
• Similar Findings Elsewhere. Referring to the UK’s response, Prof. Neil Ferguson of the Imperial College of London testified during a House of Commons committee meeting in June, “Had we introduced lockdown a week earlier we’d have reduced the final death toll by at least half.” This comment, to my knowledge, stems from analyses using the Imperial College’s COVID-19 model. I highlight it here to show that researchers around the world have come to similar conclusions about the timing and efficacy of NPIs for curbing the spread of COVID-19 and saving lives. A couple of writers from Harvard wrote an opinion piece in June published in STATNews that used the University of Oxford’s stringency index to estimate how many lives would have been saved had the US taken a faster and more holistic approach responding to the COVID threat, finding that had the US acted as effectively as Germany, at least 70% of US deaths may have been averted.
• Why? Exponential growth is a difficult thing to wrap your mind around. In just a short time, you can go from having 15 cases to having >100,000 cases and beyond. Because of the speed at which SARS-CoV-2 travels through a population (plus its ability to travel undetected for some time among asymptomatic and pre-symptomatic people), any delayed action gives the virus time and space to grow. In just 30 days between end-Feb and end-March, we went from ~40 cases/day to 25,000 cases/day! Because NPIs are so effective at curbing the virus’s spread, widespread implementation of them has sweeping impacts on the virus’s reproductive rate. This has sweeping impacts on the number of people who become infected, the ability of our health system to respond, the ability of our residential facilities (like nursing homes) to keep their residents safe, and the number of people who become seriously ill and who ultimately die.

Q&A for 9/9:

#Vaccines #DSMB

Question: What do you make of the AstraZeneka vaccine trial pause?

Answer: STATNews, which you cite in your question, broke this story yesterday and offers a good description of the issue. The AP’s reporting published this morning is also quite insightful. For those of you who haven’t read the reports, here’s a brief synthesis — AstraZeneka just paused its phase 3 clinical trial of its candidate vaccine because of a serious adverse reaction experienced by one of the participants. The Data Safety Monitoring Board (DSMB) is reviewing to make a determination. Bulleted below is a bit more information about the AstraZeneka candidate vaccine and about how DSMBs work.

As to my own thoughts — optimistic me thinks this is a good thing because: a) it shows that the scientific process is working as it should and that politics aren’t overriding safety protocols; b) it reminds us why clinical trials are so important before widespread roll out of any vaccine (or treatment); and c) it gives us some grounding by reminding us that vaccine development is challenging and that expedited timelines represent best-case scenarios. For those of you who may be more pessimistic, I’d remind you that at this stage, it’s unclear whether the adverse event was caused by or related to the vaccine; it could be a spurious association. We’ll know more after the DSMB reviews the data and makes a determination. In the meantime, don’t despair! This is the scientific process at work.

More Information on the Candidate Vaccine

• AstraZeneka and the University of Oxford have partnered to develop a new vaccine, known as AZD1222. The type of vaccine is called a viral vector vaccine. It uses a harmless virus with pieces of SARS-CoV-2 DNA to teach/prime the immune system to attack SARS-CoV-2 if it ever enters the body.
• Data from phase 1/2 clinical trial were recently shared in the Lancet. Results showed that the candidate vaccine produced intended antibody response and that mild/moderate side effects were reported among 60% of participants, but none were severe.
• AstraZeneka is in phase 3 clinical trial for its candidate vaccine, and has been aiming to recruit 300,000 participants in the US, as well as participants in the UK. Two other phase 3 clinical trials are also underway for Moderna and BioNTech/Pfizer.
• The US Government has invested at least $1.2 billion to help speed the development of AZD1222 and to reserve 400 million doses of the vaccine if/when it is ready.

More information on Data Safety Monitoring Boards (DSMBs)

• The National Institutes of Health offers an overview of DSMBs here, but it’s not the most reader friendly description. The HIV advocacy group, AVAC, offers a more reader-friendly version here.
• DSMBs are composed of independent experts, ethicists, and oftentimes community members who are not affiliated with the clinical trial and have no financial or other conflicts of interest. They review data from the clinical trial as it progresses to ensure that it is ethical to continue. This is extremely important because most clinical trials are double-blind meaning neither the participant nor the researcher knows what intervention (in this case, vaccine or placebo) they are receiving.
• We need the DSMB to review as the study progresses whether a) there is an overwhelming positive effect that would cause the study to end early because it would be unethical to continue giving participants the inferior intervention; b) there is harm caused to the participants receiving the intervention that outweighs the benefits of the intervention, which would cause the study to end early because it would be unethical to proceed (the DSMB must make a risk/benefit calculation); c) futility of continuing, meaning that the trial as designed will not answer the study question.

Q&A for 9/8:

#Number Infectious #School Reopening

Question: I only hear about the number of cases, but do we have an estimate of the number of contagious people at any time? Wouldn’t that be a helpful estimate to decide to open schools?

Answer: To my knowledge, we do not have an estimate of the number of people contagious at any given time. Instead, we generally rely on the number of daily cases, test positivity rate, and in some cases, the reproduction rate (R0) to understand whether the virus spread is growing or contracting. If we wanted to try to estimate the number of people who are infectious at any given time, we’d need to make several assumptions, including:

• At what stage of infection a person is when they are tested. Using data described in our Q&A of 9/4 #Infectivity, I suppose a fair assumption would be an infectious period of 10 days after a positive test.
• What proportion of infectious people are getting tested. To be confident that we are identifying most symptomatic and asymptomatic people, we need to be sure that we have widespread, easily accessible testing with test positivity rates <5%. If test positivity rates are higher, it means that we’re only seeing the tip of the iceberg and are not capturing the full extent of community transmission. For example, earlier in the pandemic, CDC found through seroprevalence surveys in March-May that “it is likely that greater than 10 times more SARS-CoV-2 infections occurred than the number of reported COVID-19 cases.” With testing more widespread, but test positivity still above 5% in the US as a whole (currently 5.4% 7 day rolling average), I’m not sure what the best estimate would be… For the sake of this post, I’ll make the estimate that for every positive test, there’s 1 more positive case (e.g. 1x higher than we’re finding).
• Number of people who recently tested positive. Here we want to see new daily cases.

For the US as a whole, we had 391,821 positive cases in the last 10 days. If we assume another 391,821 people are infected but not tested, then we have 783,642 infectious people in the country. You could then break this down further by smaller and smaller geographic units to get at the more community-specific estimate you’re interested in seeing. All that said, I’m not sure that this is all that helpful, because what matters SO MUCH is the degree to which these 780K+ individuals are interacting with others, how well these presumably infectious individuals are following public health protective measures, and how well non-infectious people are following public health protective measures. We know that some super-spreader events — like this recent wedding in Maine — can quickly and widely spread the virus. But how quickly the virus moves through a community is really very much about how people are interacting. This is where estimates of reproduction rates are so important!

In that vein, and as we discussed in our Q&A of 7/30 #Teachers, the school reopening indicators proposed by the American Federation of Teachers are 1) test positivity <5% and 2) reproduction rate (R0) <1. Back in late July, only 6 states met reopening criteria. I re-ran the numbers and 10 states plus DC now meet the criteria (Table 1) — California, Colorado, Connecticut, DC, Hawaii, Illinois, Maine, Massachusetts, Oregon, Rhode Island, and Vermont. Interestingly, of the 6 states that met the criteria end-July — Delaware, Maine, Michigan, New York, Ohio, and Vermont — only Main and Vermont still meet the criteria. So what does this say about schools ability to stay open if/when they do open?!

Table 1. American Federation of Teachers School Reopening

Q&A for 9/6:

#BCG

Note: No Q&A tomorrow. Happy Labor Day!

Question: Yesterday’s post on Vitamin D reminded me of another (relatively simple) approach that’s hypothesized to offer protection against infection — recent vaccine for other diseases. I think you’ve written about this in previous posts. Any updates?

Answer: Yes! We’ve discussed the hypothesis that other vaccinations — like MMR, BCG, and polio — could prove protective against COVID-19 infection (see Q&A of 6/24 #Polio and Q&A of 4/27 #TB). Now there’s a bit more research out on BCG, and here’s the scoop:

• Last week, Cell published “ACTIVATE: RCT of BCG Vaccination against Infection in the Elderly.” The study, though not focused on COVID-19, found promising results that very much relate to COVID-19. Specifically, analyzing data from their prospective, randomized control trial that included individuals ages 65+, authors found that recent BCG vaccination increased time to first infection (11 weeks among placebo vs. 16 weeks among BCG intervention), decreased the incidence of new infection (42% among placebo vs. 25% among intervention), was especially protective against viral respiratory tract infections (79% reduction in risk among BCG intervention compared with placebo), with no difference in the frequency of adverse events (i.e. it’s safe among the elderly!).
• Two weeks ago, Clinical Infectious Diseases published, “BCG vaccination in infancy does not protect against COVID-19. Evidence from a natural experiment in Sweden.” Using birth cohort data from just before and just after BCG vaccination at infancy was introduced in Sweden (i.e. around 1975), the authors tested whether BCG vaccination at birth proved protective against COVID-19 infection, hospitalization, or death in middle age. Alas, they found no such protective effect. These findings diminish the hypothesis put forward by some scientists that cross-country differences in COVID-19 incidence and severity can be attributed to BCG vaccination policy. This study cannot, however, tell us anything about the immunity benefit of recent BCG vaccination on COVID-19 incidence and outcomes.

Q&A for 9/5:

#Vitamin D

Question: It seems like Vitamin D is back in the news again. What’s the word?

Answer: Two days ago, JAMA Infectious Diseases published a new observational study, “Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results” that found statistically significant relationship between Vitamin D deficiency and COVID-19 infection (i.e. testing positive for the virus). These findings point to the need for more robust study — ideally randomized control trials (RCTs). On that front, the good news is that a number of RCTs examining Vitamin D and COVID-19 are already recruiting! Study findings also support the notion that we should be soaking up more sun and taking Vitamin D supplements to help protect against COVID-19 and other respiratory infections (in addition to protecting our bone health). So go on, follow the advice of multiple medical societies by letting some sun shine on your face every day, eating food with Vitamin D (like fatty fish, egg yolks, or foods fortified with D), and/or start taking those daily supplements! Read on for more information on the study’s findings…

We talked about Vitamin D way back in our Q&A of 4/24 (#Vitamin D), and there’s been some research published since then, including this observational study, “Vitamin D concentrations and COVID-19 infection in UK Biobank” that found no relationship between Vitamin D and susceptibility to COVID-19 infection. In contrast, this new study overcame two key limitations of the UK study — 1) it focused on Vit D levels as measured within the period 2 weeks to 12 months before positive COVID test, thereby ensuring temporal consistency (the UK study used Vit D measures from 10–14 years prior); 2) it controlled for Vit D treatment, thereby ensuring that the measure of deficiency was more precise. The new study also controlled for a host of factors, including age, sex, race, ethnicity, body mass, and a host of comorbidities including but not limited to hypertension and diabetes. In so doing, study authors found that patients with likely Vitamin D deficiency “had an increased relative risk of testing positive for COVID-19 (relative risk, 1.77; 95% CI, 1.12–2.81; P = .02) compared with patients with likely sufficient status at the time of COVID-19 testing.” Put another way, this study found that people who are likely Vitamin D deficient have a risk of testing positive for COVID-19 that is 77% higher than the risk of people who are likely Vitamin D sufficient. Now, because of the design of this study and the fact that Vitamin D deficiency could be a consequence associated with other health conditions and behaviors that increase COVID susceptibility, it’s not possible to determine a causative relationship. This is why RCTs are so important. In the meantime, because Vitamin D is safe (as long as you don’t overdo the supplements and you don’t get sunburnt), these findings add to the chorus encouraging us to boost our Vitamin D levels.

Q&A for 9/4:

#Infectivity #Test Types #Stigma

Question: Yesterday, I had to have some x-rays done at our local hospital. I told the tech that I had two negative antibody tests; he declared he’d had a positive antibody test three months ago, having had no symptoms. I asked him if he was able to transmit the virus, having had a positive result and his answer “Nobody knows!” Should I worry or hope that the hospital protocol of screening employees is appropriate? Thank you!

Answer: No need to worry! Here’s why:

• Current evidence shows that a person is infectious generally no more than 10 days after symptom onset. For a small proportion of individuals, the duration of infectivity may extend to 20 days after symptom onset (synthesized by CDC here and further described by CDC here). And we discussed the period of infectivity among asymptomatic people in our Q&A of 7/4, with evidence showing that asymptomatic people are generally infectious no more than 10 days after a positive test.
• Having antibodies does NOT mean that you have the virus or are able to transmit the virus! Testing positive for antibodies is different from testing positive for the virus; antibody tests tell you whether your body has circulating antibodies indicating previous infection while PCR/molecular tests identify active infection (Table 1).

Finally, growing stigma against people who have recovered from COVID-19 is yet another challenge we must confront. Such stigma hurts individuals, groups, and society as a whole. Among the many negative impacts of stigma, it can make curbing the pandemic much more difficult — it can make people more likely to hide symptoms, less likely to participate in contact tracing efforts, more likely to avoid seeking health care, and more! One of the key ways to confront stigma is to increase education and reduce misinformation. So please keep sharing this type of information with others!

Table 1. Different Types of COVID-19 Tests — Molecular, Antibody, and Antigen (from FDA)

Q&A for 9/3:

#Second Lockdown #Debate

Question: On Monday, Politico published excerpts of an interview with Harvard economist, James Stock, who argues that a second national lockdown would be a bad idea. What do you think about these Harvard professor’s views on the need for another lockdown?

Answer: This is an important debate going on in the country (and around the world) about whether a second lockdown is required. I’m going to describe both sides of the argument and then tell you where I land, for what it’s worth.

Argument A: We Need a Second Lockdown

A number of health professionals have been calling for a second national lockdown to contain the virus. Perhaps the largest push has been through the collective effort of U.S. PIRG through an open letter to President Trump, which has been signed by >1,000 health professionals. The letter was released on 29 July. The basic argument is:

1. Background: Our original national lockdown prevented millions of cases and saved hundreds of thousands of lives. For example, this article published in Nature shows that lockdown resulted in 4.8 million fewer cases in the US as of 6 April.
2. Problem statement: Lockdown was lifted too quickly in favor of reopening, and was done so before necessary public health infrastructure and policies were in place to further contain viral spread. We cannot restore the economy until we contain the virus. Without national mask mandates and with numerous states allowing for non-essential activities that carry greater risk (like drinking at indoor bars), the country is on track to suffer an estimated 300,000 deaths by the start of December.
3. Solution: If we are going to get COVID-19 under control and thereby get our economy going, we must have a stringent national lockdown. As described by U.S. PIRG, this means that non-essential businesses should be closed with restaurant service limited to take-out. People should stay home, going out only to get food and medicine or to exercise and get fresh air. Masks should be mandatory in all situations, indoors and outdoors, where we interact with others. And non-essential interstate travel should be barred. Reopening should then only be done in the context where we have 1) Enough testing; 2) Sufficient contact tracing; 3) Sufficient personal protective equipment (Figure 1).

Argument B: Shutdown Is Neither Necessary Nor Desirable

As described in the Politico article you cite as well as this Brookings article, “Policies for a Second Wave,” here the basic argument is:

1. Background: Economic shutdown, combined with non-pharmaceutical interventions (NPIs, e.g. mask wearing, keeping 6-feet distance, etc.) did lead to reductions in cases, deaths, and the viral reproductive rate. However, the national lockdown also triggered the sharpest and deepest recession since the Great Depression.
2. Problem statement: National lockdown would bring increased economic misery. It would also mean that the government has learned nothing over the last six months and is not taking responsibility for effective action (e.g. shutdown allows the government to be “off the hook” for mandating masks, providing millions of dollars to fund testing, and the like). We cannot restore the economy until we contain the virus, however “there is strong evidence that much of the decline in economic activity was the result of self-protective behavior by individuals, not government shutdown orders, so simply reversing those orders will not by itself revive the economy.”
3. Solution: A second wave can be prevented or reversed “through the adoption of non-economic NPIs, without needing to close either schools or the economy.” As described by David Baquaee, James Stock and colleagues in this conference paper, “non-economic non-pharmaceutical interventions, such as reintroducing restrictions on social and recreational gatherings, stressing wearing masks and personal distancing, increasing testing and quarantine, and enhancing protections for the elderly and the most vulnerable, together can mitigate a second wave while leaving room for an economic recovery.” Here the virus is contained and lives are saved, and businesses remain open under CDC guidelines AND with strict precautions carried out outside of work, including widespread masking, testing, isolation, social distancing, enhanced protections for the elderly, and prohibitions on high-contact economic activity (like theaters, sporting events, bars).

Where I Stand

What I hope you’ll see after reading these descriptions is that the two arguments actually aren’t all that different. Both call for widespread masking, testing, contact tracing, social distancing, and the like. Argument A positions that the virus is too out of control for testing, contact tracing, and isolation to work, thereby requiring a second lockdown. Argument B positions that a second lockdown would give too much political cover for effective policies — including masking, testing, contact tracing — to be promoted, funded, and implemented. Moreover, a second lockdown would only bring more economic misery. Writing this post today (which means that my prerogative might change next week or next month or next year), I lean to Argument B. We squandered so much of time that the original national lockdown gave us (see Q&A of 6/25, Q&A of 4/19, and Q&A of 3/24); I don’t think that a second national lockdown would have a different result. That said, I absolutely agree with both arguments that we need enough testing, contact tracing, support for isolation, personal protective equipment, as well as mask mandates and implementation of strict precautions in businesses and schools, enhanced protections for high-risk populations (like older people) and prohibitions on high-contact economic activities. These needs are costly and aren’t fun, but they are necessary and they will allow us to curb the virus so that we can prevent infections, save lives, restore our economy, and ultimately get back to all the people and activities we love.

Figure 1. Excerpt from U.S. PIRG Open Letter (here)

Q&A for 9/2:

#Kids #Testing #Cases

Question: Here’s a question that I’ve had for a few weeks, but I held back from asking since you were on vacation. :) So I was reading news reports that in the last two weeks of July, ~100,000 children tested positive for COVID-19. Is this true?

Answer: Thanks for remembering your question and still asking! Short answer to your question is yes, these estimates are true, subject to the limitations of the underlying data used to conduct the analysis. And now the longer answer.

Cases, particularly cases among children, dramatically increased in mid/late July

In August, the American Academy of Pediatrics and the Children’s Hospital Association conducted an analysis to understand the scope of COVID-19 infections, hospitalizations, and deaths among children in the United States (where state-level age-specific data were available). Findings are summarized in Figure 1. One of the findings that generated a lot of news interest is that COVID-19 cases among children increased 40% in just 15 days — rising from a total 241,904 as of 7/15 to 338,982 as of 7/30.

When I read this astounding figure, I wondered how this compared to the rise in overall cases, regardless of age. So I ran a quick analysis using data from covidtracking.com and found that over the same 15 day period in mid/late July, total cases in the US increased 28%! To put that in perspective — the US has been reporting COVID cases every day since February 28th; so in just 15 days, we saw a nearly 30% increase in cases from the cumulative total of the previous 139 days! Whew! That’s exponential growth for you. What this also means is that cases among children were growing at a faster rate than cases among adults.

Cases among children are likely an underestimate

What’s also important to recognize is that the number of cases among children is likely an underestimate. Data presented last week in an article published in JAMA Pediatrics, “Clinical Characteristics and Viral RNA Detection in Children With Coronavirus Disease 2019 in the Republic of Korea” and further described in this accompanying editorial show that “not all infected children have symptoms, and even those with symptoms are not necessarily recognized in a timely fashion… This highlights the concept that infected children may be more likely to go unnoticed either with or without symptoms and continue on with their usual activities, which may contribute to viral circulation within their community.”

We have no national system for monitoring testing

One thing this analysis highlights is that the study authors had to laboriously collect testing data by age on a state-by-state basis with states reporting age distribution in different ways, using different definitions, and some states not reporting age distributions at all. Why should it be so difficult?! This lack of national testing data is unacceptable — it precludes other important analyses and insights. For example, we know that COVID disproportionately impacts Blacks, Hispanics, and American Indians. It would therefore be important to observe testing not only by age or race, but by age AND race. Data availability and completeness (not just for testing, but for cases and hospitalizations) in the US makes this type of analysis a shockingly challenging undertaking.

Figure 1. Children and COVID-19 as of 30 July (from AAP report)

Q&A for 9/1:

#School #Universal Testing

Question: I read an article about Rochester Institute of Technology in NY requiring students to get tested before they showed up at college and to bring their negative test result as proof to get onto campus. Why aren’t all schools doing that? Seems like a best practice to prevent spread in the first place?

Answer: We talked about school reopening in our Q&As of 7/30 (#Teachers), 7/28 (#Private School) and 7/27 (#School Reopening), but haven’t directly talked about universal testing. I’m afraid there’s not a straightforward answer to your question…

On the one hand, contrary to your suggestion that universal testing would be a best practice, CDC’s considerations for testing in K-12 schools states, “CDC does not recommend universal testing of all students and staff.” Figure 1 is a screenshot of the full paragraph. Here, the issue is lack of evidence supporting universal testing coupled with implementation challenges. Because testing limitations abound — including time to receive results and the possibility of false negative results (more on false negatives, see Q&A of 7/3 #False Negative) — universal testing would still be insufficient to curtail the spread. Other key interventions — like mask wearing, classroom cohorting, improved ventilation, expanded cleaning/disinfection, daily health checks — would need to continue to be followed. Indeed, as reported last week in CDC’s Morbidity and Mortality Weekly Report, Rhode Island Child Care Centers were able to curtail secondary transmission without using universal testing. Rather, cohorting in small class groups, universal mask wearing by all adults, daily symptom screening of adults and children, and enhanced cleaning and disinfection according to CDC guidelines kept secondary transmission at bay. The authors concluded,”Possible secondary transmission was identified in four of the 666 programs that had been allowed to reopen, all in the last 2 weeks of July, when community transmission in Rhode Island increased. The apparent absence of secondary transmission within the other 662 child care programs was likely the result of RIDOH response efforts to contain transmission and child care programs’ adherence to RIDHS requirements, in particular maximum class sizes and use of face masks for adults.”

On the other hand, when it comes to keeping kids and young adults safe in residential learning facilities like sleep-away camps and residential colleges, the recent experiences of summer camps in Maine offer some important guidance for the way forward. As reported just a few days ago in CDC’s Morbidity and Mortality Weekly Report, the experiences of four different camps in Maine DO point to the utility of universal testing as part of a multifaceted prevention and mitigation strategy (Figure 2). This multifaceted approach included “precamp quarantine, pre- and post-arrival testing and symptom screening, cohorting, and physical distancing between cohorts. In addition, camps required use of face coverings, enhanced hygiene measures, enhanced cleaning and disinfecting, maximal outdoor programming, and early and rapid identification of infection and isolation.” And thanks to these measures, the camps were “successful in identifying and isolating three asymptomatic COVID-19 cases and preventing secondary transmission.” Here testing before arrival was a key component of the strategy and it did have utility.

Figure 1. CDC Recommends Against Universal Testing in K-12 Schools (from CDC)

Figure 2. Multifaceted COVID Prevention and Mitigation in 4 Maine Sleepaway Camps (from CDC)

Q&A for 8/31:

#Vaccines #Antibodies #Lasting Immunity

Question: Follow-up question to Saturday’s post — If having antibodies doesn’t confer immunity, then what would be the point of a vaccine? And if you can get it over and over again, are we doomed to socially distance forever?

Answer: Take heart, we are not doomed to socially distance forever! And thanks for this question, which gives me the opportunity to clarify a few things from our Q&A of 8/29:

Antibodies and immunity. To my knowledge the majority of health experts believe that antibodies do confer some degree of protection. What remains unclear is the strength of the protection afforded and how long such protection lasts. Second, because the immune system is complex, even if antibodies quickly dissipate, evidence is mounting that the protection conferred by T-cells is long-lasting (see Q&A of 5/17 and Q&A of 8/6 #Immunity). This means that even if tests do not detect any antibodies, a person may still have lasting protection — either from previous infection or from vaccination — thanks to their T-cells (for refresh on immune system, see Q&A of 5/9 #Immune Response).

Vaccines. We discussed similar questions in our Q&A of 4/25 (#Vaccines) and further discussed vaccine effectiveness in our Q&A of 7/8 (#Vaccination Effectiveness). So far, evidence that has been made publicly available on vaccination trials underway indicates that vaccinations in clinical trials are eliciting an immune response (yay!) and as summarized recently by scientists at Johns Hopkins, “Evidence from these clinical trials, and from preclinical studies in rhesus macaques, suggests that this inactivated vaccine is not associated with antibody-dependent enhancement (ADE) or vaccine-associated enhanced respiratory disease (VAERD)” (double yay!). Even if protection does wane over time, we would likely take booster shots in response. And even if we were to get infected after vaccination, we would likely become sick with a less severe form of disease (including asymptomatic infection). This article published a few days ago in STAT News, “Four scenarios on how we might develop immunity to Covid-19”, offers a nice synthesis of the lasting immunity unknowns and hypotheses. The upshot is — accumulating evidence coupled with historic experience indicates that vaccines will offer protection!

Waiting for a vaccine. As a reminder, plenty of places in the world, including New York State, have managed to get the virus under control without a vaccine. If we could get community transmission under control, we could then rely on testing, contact tracing, and isolation to monitor and curtail spread without widespread lock-down measures. This requires public health investment, community trust, and individual and social engagement (including mask wearing).

Q&A for 8/30:

#USA #NYS #DC #MD

Question: It’s been a while since we checked in on trends in COVID cases, hospitalizations, and deaths. How are things looking in NYS and elsewhere?

Answer: It has been some time since we looked at trends. Below are charts I made using data from covidtracking.com for USA, New York State, DC, and Maryland. Here’s the upshot for each of the charts:

Figure 1. USA: Cases, hospitalizations, and test positivity are trending down since their most recent peak in late-July, which is a good thing. That said, cases are still high with a 7-day rolling average of ~41,000/day and test positivity is still high with a 7-day rolling average of 5.9%. Meanwhile, testing is still below its peak of late-July. The United States has much work to do to get the pandemic under control. And can take a lot of learning from New York(!), which is my segue to Figure 2.

Figure 2. NYS: Very impressive. Since getting the pandemic under control, New York has so far managed to prevent a second wave. This is exactly what we want to see!

Figure 3. DC: DC is looking pretty good. Test positivity is low and cases have once again fallen since they started to rise in July. That said, cases are still below their low of late-June/early-July and hospitalizations have plateaued. There’s still work to be done even in light of these successes.

Figure 4: MD: Maryland’s experience more mirrors the country’s. Like the county as a whole, testing has decreased (not good), but cases, hospitalizations, and test positivity are on the right downward trajectory. Although cases and hospitalizations are still higher than their late-June lows, test positivity is 4.5%, which is about as low as it has ever been. Clearly, there is still much work to be done, but it is nonetheless heartening to see that the end of August is looking better than its start.

Figure 1. USA

Figure 2. NYS

Figure 3. DC

Figure 4. MD

Q&A for 8/29:

#Antibody Tests #T-cells

Question: I know you’ve already talked about antibodies and antibody tests before, but the recent NYTimes article, “Why Antibody Tests Won’t Help You Much,” made me want to know what an effective antibody test would look like. What should they be testing for if they want to know if you’ve actually had it (assuming that having had it confer immunity for at least a couple of years)?

Answer: Yes, we have talked a good deal about antibody testing over the months (see Q&As of 4/13 #Antibody, 4/15 #Specificity, 5/21 #Monitoring, and 8/7 #Immunity), but there’s always more to write because we’re always learning more! To summarize the Times article for those who haven’t read it — the Infectious Disease Society of America released guidelines on antibody (serologic) testing earlier this month, which concluded with 8 recommendations, including:

1. Don’t use antibody tests to make individual-level decisions about risk. “Based on the available evidence at this time, serologic tests should not be used to determine immunity or risk of re-infection. Thus, anti-SARS-CoV-2 antibody detection cannot inform decisions to discontinue physical distancing or lessen the use of personal protective equipment.”
2. Do use antibody tests for population-based epidemiologic studies and in 2 clinical scenarios. “In addition to use in epidemiologic studies, the panel identified two clinical scenarios where antibody testing was felt to have potential utility for diagnosis…[1] Serologic testing may be helpful in the evaluation of individual patients with a high clinical suspicion for COVID-19 when the results of molecular diagnostic testing are repeatedly negative or such testing was not performed…[2] Detection of anti-SARS-CoV-2 antibodies is also useful for assessments of suspected multisystem inflammatory syndrome in children.” Now to get back to your question…

What should they be testing for if they want to know if you’ve actually had it (assuming that having had it confer immunity for at least a couple of years)?

Here the challenge is that we still don’t know how long after infection immunity lasts, how robust our immune response would be in response to potential reinfection, and whether immune response would differ by a/symptomatic status. The assumption underlying your question — which is the major assumption underlying the purpose of individual-level antibody testing — is still just an assumption. In fact, we have accumulating evidence that antibodies decline quite rapidly after COVID-19 infection, especially among asymptomatic individuals. For example, this small study out of China published in Nature found that 40% of asymptomatic patients became seronegative within 8 weeks of hospital discharge. This article from GAVI gives a nice overview of the issues. So even if we had the perfect antibody test, it still might not be telling us individually anything of significance. Here, we need more information on lasting immunity, reinfection, and the like. Since antibodies are only one component of our complex immune systems, we also need more information on whether immunity lasts regardless of presence/absence of antibodies. Here is another promising avenue for research — the study of T-cells.

Testing for T-cells

Since T-cell immunity may last longer than B-cell immunity (B-cell antibodies are detected in current antibody tests), a bigger push of late has been to study T-cell immunity (as discussed in Q&A of 8/6 #T-cells). For example, a study out of Sweden published in Cell a couple of weeks ago found among other interesting results, that “memory T cell responses were elicited in the absence or presence of circulating antibodies.” This seems very promising. However(!), we still don’t know what degree of immunity lasting T-cell response confers. And as described in the aforementioned GAVI article, “as T cells only respond to the virus once it has already invaded host cells, there is a possibility that people may still be able to transmit the virus even if they do not themselves develop disease.” Finally, T-cells are harder to measure than antibodies, but there are tests that do allow for it.

Q&A for 8/28:

#Excess Mortality

Question: Going back to the excess mortality post from earlier in the week, if I remember correctly, and judging by these data on U.S. mortality changes over time, mortality in the United States has been increasing since ~2013. How do the increases in mortality over the COVID period compare with increases in mortality over the last several years? More specifically, I’m thinking that since the UN projected (pre-pandemic) that deaths in the United States in 2020 would be higher than those in 2019, are we really seeing increases that are much bigger than projected?

Answer: We talked about excess deaths in our Q&A of 8/24 (#Excess Mortality), and your question allows us to dig deeper, so let’s do it! Using data from CDC’s National Center for Health Statistics, which collects mortality data for the country, we see that deaths are increasing MUCH faster than in previous years — even with incomplete reports for the first 32 weeks of 2020, deaths are 13% higher than the first 32 weeks of 2019 (Table 1). If we were to use UN World Population Prospects 2019 estimates for the US (which were published in mid-2019, pre-pandemic and use US official estimates of 2016 and 2017 to extrapolate), we would assume the following for 2020:

• Crude death rate: 8.8 per 1,000 individuals
• Total population estimate: 331,003,000
• Total expected deaths for 2020 (52 weeks): 2,912,826
• Total expected deaths for 2020 (32 weeks): 1,792,509
• Difference between expected and realized deaths: 204,550

Table 1. Yearly Deaths in the United States

Q&A for 8/27:

#Face masks #Decisions

Question: What kind of mask should my child wear to school? Which adult mask do you recommend? What are some things I should look for when purchasing a mask? Every vendor appears to be selling a mask (from Nordstrom to Nike), but they come with a host of warnings such as “not meant as barrier protection.” I have decision fatigue and just want someone knowledgeable to give me some recommendations.

Answer: I was faced with this same issue the other day when I was online, saw a set of masks on sale, and then spent too much time trying to figure out what material they were made of, ultimately ending up exhausted and just turning off the computer. But it doesn’t need to be that hard! Here is the very simple guidance: just look for 2+ layer cotton masks *without* a valve and you’ll be good. And here’s more detail:

First, we need to keep with cloth masks for the time being as we’re still reserving surgical masks and N95s for healthcare workers. Second, per CDC, you want your cloth mask to be: ideally made of cotton; at least two layers thick; and with NO valve. When it comes to kids ages 2+ (and adults too for that matter), it’s best to find them a mask that they are happy(ier) to wear and that is comfy enough that they aren’t all the time adjusting it. For that reason, I suggest buying/trying a few different types of masks (e.g. brands, ear loops/ear ties, pleated/flat; with/without bendable border at the top to accommodate glasses) and choosing patterns or colors that your kids like. If your kid is up for it, invite them to participate in choosing their masks. This article from NBC offers some advice for kids masks and this one from the NY Times offers some advice for adult masks, though both articles seem to be a bit sales-pitchy. When it comes to my own mask wearing, I have an awesome neighbor that made us a few simple cloth masks that I really like. And we have a family friend, Judy DePalma, a clothing designer who turned to making cloth masks earlier this year; I often use her masks too.