Another Round of COVID Confusion

You heard: Breakthrough infections are uncommon.

What that means: Breakthrough infections are uncommon when you look at the totality of data spanning from when vaccines began to be rolled out in December 2020. The New York Times and other papers often cite a Kaiser Family Foundation report that states Almost all (more than 9 in 10) COVID-19 cases, hospitalizations, and deaths have occurred among people who are unvaccinated or not yet fully vaccinated, in those states reporting breakthrough data (see Figure 2). But data from last spring does not necessarily capture the current picture.

We expect breakthrough infections to become more frequent as more Americans get vaccinated.

We expect breakthrough infections to become more frequent as COVID cases rise, driven by explosive growth in unvaccinated people.

The US is beginning a major Delta wave.

Moreover, there appears to be a higher rate of breakthrough cases since Delta variants ripped across the country this summer, even controlling for the larger population of vaccinated people compared to last spring. See the figure below from Dane County, Wisconsin (yes, it would be useful to have this kind of figure for nationwide data but America has crippling data collection problems). The 7-day rate of infection for unvaccinated residents is almost 3x times higher than fully vaccinated residents (29.1 versus 10.5 per 100,000), showing that vaccines do work. Still, with 68% of the population vaccinated (including 79% of eligible people), this still means many of the cases will be breakthrough (43% breakthrough/57% unvaccinated).

But it’s important not to conflate rising breakthrough cases with reduced effectiveness of the vaccine. It’s always compared to what?

Data from Dane County, Wisconsin. Breakthrough cases per 100,000 of the vaccinated population surge following the emergence of Delta

You heard: Protection from the vaccine is waning and I need a third shot booster.

What that means: Israel was supposed to be the poster child for an effective vaccine campaign that beat back COVID. The country not only received an early supply of Pfizer vaccine but benefits from a highly monitored health system to track the vaccine’s impact. Over 78% of the eligible population was vaccinated by July 1, 2021 and COVID deaths had sunk to zero for the first time since the start of the pandemic. Data was showing that COVID-19 vaccines were not only effective in preventing hospitalization and death, but also in blocking infection and transmission. The feared spring wave of UK Alpha variants never materialized in Israel or the US the way it did in European countries with lower vaccine rates. Vaccine offered salvation. Until it didn’t.

There has been a lot of handwringing about vaccines not working anymore. It sounds bad when of the 515 patients currently hospitalized with severe cases in Israel nearly 60% are vaccinated. Media outlets have quoted this figure to suggest that vaccine effectiveness has waned and third shot boosters are needed.

A helpful COVID-19 Data Science post explains step-by-step how appropriately stratifying by age can change the interpretation of vaccine effectiveness (VE) data. If you’re reading oversimplified VE percentages in the media that are not age-stratified, you should just ignore them. Here’s why:

  1. Nearly all older people were vaccinated (>90% of residents >50yr) while the vast majority of unvaccinated are younger people (>85% of unvaccinated <50yr)
  2. Older people are orders of magnitude more likely to be hospitalized than young people. Those >50yr are >20x more likely to be hospitalized compared to <50yr and for 90+ are the difference is >1600x more. These are enormous confounders.
Israeli data on severe hospitalized COVID cases split into crude age groups (below and over 50 years)

If you estimate VE without taking into account age you get 67.5%, which means 2/3 of severe cases are prevented by vaccine. Pretty good, but not as good as the previously touted 90-95% range.

But….if you take into consideration the fact that more vaccinated people are old and much more likely to get hospitalized in the first place (91.9 versus 3.9 in unvaccinated group = 23x more likely) things start to look a lot better. VE for younger people is 91% (1 – 0.3/3.9) and VE for older than 50 is 85% (1 – 13.6/91.9). VE is expected to be lower for older people who don’t mount as good immune responses. In fact, VE might drop quite a bit for 70+ and 80+ if you further stratify by age (bumping up the VE for 50-59). But overall these are good numbers and the vaccine is performing well against Delta in protecting people against severe disease. It may seem statistically impossible that 85% VE + 91% VE = 67% VE (combined), but that just shows how important the age-stratification is.

How well the vaccine protects against mild infection with Delta is another question that requires deeper data.

Later in September the FDA is expected to approve third shot boosters of mRNA vaccines for everyone and the shots will be available 8 months from the date of your second dose (since I got my second shot in May, the third shot would not be until January). In the mean time I recognize that vaccines are not 100% effective and do not give me license to party like it’s 2019. I am grateful that I live in a country where vaccine supply is plentiful and all the adults in my family are well protected against severe disease, allowing grandparents to see their grandchildren. I have no problem wearing a mask inside public spaces for as long as it takes for COVID to become managed. Personally, unless there is irrefutable data that vaccine effectiveness has plummeted I would rather give my booster shot to someone at high risk in a developing country who hasn’t even gotten one dose. Beating COVID in America requires altruist behavior: people acting not just in immediate self-interest but making sacrifices for the larger community, including the vulnerable and children. How can we expect Americans to behave altruistically when the country itself is not acting altruistically towards other countries? When will we begin modeling the behavior we desperately need to promote? Moreover, helping other countries is not just altruistic; containing COVID in other countries will reduce the likelihood of new variants emerging overseas. The more viruses circulating, the more opportunity for new mutants to arise. Not only are SARS-CoV-2 viruses capable of evolving by mutation, but they can swap entire stretches of genetic material with each other through recombination (a version of viral “mating”).

Delta is the most recent variant to takeover globally but other alarming variants are already circulating. So far nothing has emerged that outpaces Delta, but it could be a matter of time.

You heard: Delta variants are as contagious as chickenpox.

What that means: The Delta variant is estimated to have a higher R (reproductive number) than prior COVID strains, which means each infected persons pass on the virus to more people. The SARS-CoV-2 virus has been evolving rapidly since it emerged in humans into progressively fitter and more contagious forms. Prior to Delta, Alpha was considered the most transmissible variant, but has now been displaced by Delta.

Keep in mind that R is an average. Since SARS-CoV-2 is a good superspreader there will be a lot of variation in transmission. Many infected people will pass the virus on to no one. A small number will infect dozens. That’s why large gatherings are so problematic. If the infected person was capped out at passing the virus to only 7 people there would not be such a problem. But when a person who happens to be a superspreader (some people just shed a lot of virus) finds themselves in a densely packed gathering, the virus can rip through and infect numbers much, much larger than 7.

Being an average, R can also vary geographically based on local contact patterns. R in rural farm country where no mass gatherings occur will be a lot lower than in urban neighborhoods or tourist destinations that get densely packed. It is an open question the extent to which the elevated estimations of R for Delta reflect intrinsic properties of the virus versus sudden changes in human contact patterns in July and August when Americans loosened social distancing and stopped wearing masks.

You heard: Viral loads are similar in vaccinated and unvaccinated people.

What that means: Viral loads represent the amount of replicating virus. Higher viral loads can lead to more symptomatic disease and/or higher likelihood of transmitting the virus to another person.

There is data showing similar viral loads in vaccinated and unvaccinated people.

But you get a more complete picture when you look at the time course of viral load. There are similar loads early in the infection when transmission occurs. But eventually an immune system primed by a vaccine is able to bring down the viral load much faster than a naive immune response, reducing the risk of severe disease and curtailing the period of infectiousness to other people. There is still a lot we need to learn about Delta, vaccines, and transmission, but in the mean time vaccinated people should recognize that the vaccine is good at protecting you but does not necessarily remove the risk of infecting others. That is why it is particularly important for vaccinated people to continue distancing when possible and wearing masks in dense or poorly ventilated spaces.

You heard: The Delta wave is primarily a problem in the South.

What that means: The Delta wave has spread everywhere. This summer’s epicenter in Southern states mirrors what happened last summer when COVID defied the expectation of being a winter disease that would fade as temperatures warmed, instead during in hot states where people crowd into air-conditioned buildings and spend less time outdoors during summer months. Lower vaccination rates and less social distancing in the South exacerbates the problem, but we saw this same pattern last year when vaccine was not a factor. Wildfire and smoke that keep people indoors in Western states could also drive up transmission in those areas.

The top-10 states with most new daily confirmed COVID cases per 100k population are all located in the South

The surge appears driven by younger people who tend to have lower and more variable vaccination rates across US states.

Highest rates of infection are in young adults.
Vaccination rates are generally high in older people in every state, but gulfs emerge in younger people.

You heard: The current wave is not a big deal because old people are protected so it’s just mild infections.

What that means: Louisiana, Florida and Oregon have reported record hospitalizations in recent weeks as the Delta variant spreads. Recall that hospitalization and death are lagging indicators which means that we won’t observe the real toll of the current surge in cases for several weeks.

Delta wave in Oregon (blue is hospitalizations)

COVID becomes even more lethal when heart attack and car accident victims can’t get a hospital bed. Even pediatric wards are filling up. I challenge anyone who doesn’t think COVID is a big deal right now to volunteer one hour’s time in an over-crowded ICU. Our doctors, nurses, and staff were already seriously burned out going into the summer. August is supposed to be the quiet before the storm when flu season hits in the fall. Exhausted medical staff are more likely to make mistakes. Overtaxing our medical systems has serious knock-on effects.

Oregon’s hospitals are reaching capacity

You heard: Mild cases are okay. In fact, mild infections in vaccinated people could serve as a natural booster.

What that means: There is a tendency in the press to downplay “mild” COVID cases. Yes, a week or two fevering in bed is something we can all tough out. But we all know healthy people who have had seemingly mild cases turn into long-running complications, either cardiovascular, neurological, or pulmonary. Mild breakthrough infections also appear to be able to cause “long COVID” but of course we need better longitudinal data for Delta. Our health tracking systems are not well designed to study long-term COVID complications so methodologically there is a lot we still don’t know.

You heard: Delta is sending more kids to the hospital.

What that means: The rate of hospitalization of kids with COVID is increasing, but the overall risk is still low. But kids are more susceptible to a range of respiratory viruses, including RSV and flu. RSV and flu were both suppressed by school closures last year and there is a risk when school starts of kicking off outbreaks of other respiratory infections in kids whose immune systems have been dormant for a year. A big concern that pediatric wards filled with kids with other respiratory infections might not have capacity for the additional kids that enter with COVID. Even more reason for schools not to be complacent prepared this year. A lot of schools are drawing on last year’s experience to assume that transmission will be low in kids. But Delta is more transmissible and strategies that worked last year may be less effective this year. We owe it to our kids to bring our A game this fall. That means routine testing in schools (pooled if necessary), intensive contact tracing, tents for outdoor lunches, extra teachers for smaller class sizes, mandatory vaccination of teachers and staff, extra staff for facilitating online learning for kids that have to be temporarily isolated at home (any kid with a sniffle could miss school until they get a negative COVID test — just wait until cold season hits).

Why is it taking so long for vaccine to become available for kids <12? The clinical trials for young kids are much smaller, enrolling one-tenth the number as were in the adult trials, which means they require a longer period of data-gathering to achieve sufficient power. Contrary to widespread perception that COVID trials in adults were “rushed”, the trials simply benefited from “blank check” cash influxes that allowed enormous numbers of volunteers to be enrolled to power the study. Not having to wait around for people to get infected also sped up the trials (the *one* benefit of letting COVID rip through the globe).

You heard: COVID vaccines cause sterility.

What that means: You get your news from the wrong sources.

Here’s an example of a rare side effect of the COVID vaccine in children that legitimately occurs and has received attention. An outsized number of vaccinated people (particularly boys ages 18-24) experienced myocarditis (inflammation of the heart). However, the rate of myocarditis is still very rare even in the highest risk category (219 out of >4 million) and the condition generally recedes after a few months. Media headlines about heart inflammation in kids naturally cause anxiety in parents, but this is an exceedingly small risk compared to getting naturally infected with COVID.

You heard: CDC recently changed its guidance on mask wearing for vaccinated people.

What that means: Effectively, that Americans now have no idea when they are supposed to wear masks.

What prompted the change? The CDC changed the mask guidance for vaccinated people after seeing the data from an outbreak in Provincetown, Massachusetts during Fourth of July festivities. The vast majority (74%) of the 469 COVID-19 cases from the Provincetown outbreak were in fully vaccinated people. Most of this population was adult males (average age 40). Almost all the viruses were Delta (90%). Overall, 274 (79%) vaccinated patients with breakthrough infection were symptomatic (although asymptomatic cases were likely missed). Measures of viral load in vaccinated people who got infected were similar to those who were unvaccinated (viral load is often used as a proxy for contagiousness). Five COVID-19 patients were hospitalized, four who were fully vaccinated; no deaths were reported. The data was difficult to interpret because it was not age-stratified.

What are the changes for fully vaccinated people?

CDC addition: Wear a mask in public indoor settings in areas of “substantial or high transmission”.

My translation: At first I thought this meant “settings with high transmission” like bars, restaurants, buses, but if you click the link it means US counties with high COVID activity. Which includes almost all counties, even in Vermont. So really this is just: “Wear a mask in all public indoor settings“. What does “public” encompass? My interpretation includes any place you encounter strangers, including private businesses.


CDC addition: Wear a mask regardless of the level of transmission, particularly if they are immunocompromised or at increased risk for severe disease from COVID-19, or if they have someone in their household who is immunocompromised, at increased risk of severe disease or not fully vaccinated.

My translation: You should already be doing this (see above)


CDC addition: Fully vaccinated people who have come into close contact with someone with suspected or confirmed COVID-19 to be tested 3-5 days after exposure, and to wear a mask in public indoor settings for 14 days or until they receive a negative test result.

My translation: You should already be doing this (see above).


CDC addition: CDC recommends universal indoor masking for all teachers, staff, students, and visitors to schools, regardless of vaccination status.

My translation: You should already be doing this (see above).

The Day I Got Harassed For Jogging Without a Mask

“Wear a mask!”

I stopped running and wheeled around to face the voice. “Pardon me?” A middle-aged woman ambled towards me on DC’s Glover-Archibald hiking trail. She was alone and walked with a long stick.

“Wear a mask!” she shouted again, closing to within five yards of me.

My arm hairs went erect and my heart pounded, but I stood my ground. “Don’t. Judge. Me,” I glowered.  

“I’m not judging you, I just want you to wear a mask,” she prattled on, continuing to approach me. She was overweight and did not walk easily. “What are you, a Trumpie?”

“You know nothing about me.” I stared into her dull grey eyes, buried beneath a sagging forehead.

“I know you’re the reason 300,00 people are dead. Selfish people like you who don’t care.”

“You don’t think I care?”

“No! You’re selfish.” She caught up to me on the trail and we now walked side-by-side. It was a brisk November day, and my running sweat was already giving me a chill.

I smiled. “I thought you weren’t judging me.”

“I AM judging you!” she decided. “You deserved to be judged.”

I began to describe what she could not see: that I was the least likely person to transmit COVID to her, that I rarely left my house except to jog outside, and that I rarely wore a mask because I was rarely indoors or around people. I did not even go to the grocery store and my family bubble was tight. Moreover, I was an infectious disease epidemiologist working every day for the nation’s premier research center to save the world from COVID and other pandemic threats, just to keep people like her safe. I spent nights writing my COVID blog to help people navigate confusing times without losing their minds, even after I got a concussion after falling off a horse. I answered readers’ COVID questions until my headaches made it impossible. But not wearing a mask on a jog turned me into the bad guy. How simple people wanted the world to be.  

But the trail was narrowing and we had lost our physical distance and sudden I became the one who felt unsafe, realizing I was in the “spew radius” of an unhinged stranger who was spitting as she yelled, not paying attention to her physical distance, and not wearing her mask properly. I wanted to say more about her misunderstandings, but I decided it was best to move on. I offered a cheerful “Well, have a good day!” over my shoulder as I trotted away, adding “Try not to judge people!”

I had been running in those woods for twenty years; she looked like she had never hiked a day in her life. Her harsh words could not sting me on my turf, under my oaks. But as I trotted home I knew our country was fucked. The mask issue had gone too far. People were no longer being rational. I understood why the woman yelled at me; she was scared. The pandemic was ripping through America, gunning for older, overweight people like her. She wanted to feel safe and my naked face seemed threatening. She was terrified by the image of invisible bugs emanating from my breath, carried along thermals into her nose. A mask had become a short-cut barometer for evaluating who was safe and who was not. America had found a new dividing line between sinner and saints. Only it had strayed too far from science.  

The Coming COVID-19 War: Vaccinating Children

If you thought controversies over masks and lab-leaks were fever pitched, just hold your hats until the COVID-19 vaccine is licensed for kids under 12 this fall. Nothing gets Americans lathered up like policies that affect the safety of their kids. The diversity of opinions on this matter is about to skyrocket because the cost-benefits of vaccinating America’s 50 million kids ages 0-11 for COVID-19 is not nearly as straightforwards as it would be for pandemic influenza, for which kids are one of the highest risk groups for severe disease. Here’s a sneak peak of what’s to come.

Universal recommendation for vaccinating kids with underlying conditions. There will be scientific consensus on vaccinating kids with underlying conditions (asthma, obesity, diabetes, autoimmune disorders, etc.) who are at higher risk for hospitalization and death. This is not a small group of kids. Obesity has been surging in children for decades and BMI is over the 95th percentile in age/sex-specific growth charts for 13.4% of 2- to 5-year-olds and 20.3% of 6- to 11-year-olds.

Percentage of US children obese. Obesity is body mass index (BMI) at or above the 95th percentile from the sex-specific BMI-for-age 2000 CDC Growth Charts.
SOURCES: National Center for Health Statistics, National Health Examination Surveys II (ages 6–11), III (ages 12–17); and National Health and Nutrition Examination Surveys (NHANES) I–III, and NHANES 1999–2000, 2001–2002, 2003–2004, 2005–2006, 2007–2008, 2009–2010, 2011–2012, 2013–2014, 2015–2016, and 2017–2018.

Should healthy US kids get vaccine before high-risk adults in countries with low vaccine supply? Honestly, I don’t know what my answer would be if given the option to voluntarily donate my child’s COVID-19 to an at-risk adult in an African country being ravaged by COVID-19 and desperately in need of vaccine. If I put on my economist hat and weigh costs and benefits, of course I should rationally and ethically donate the vaccine. There is a vanishingly small chance of COVID-19 killing my two-year old. Moreover, controlling SARS-CoV-2 overseas makes it less likely that an even more dangerous variant will evolve and make its way to America, just as India’s Delta variant is now. But wearing my mom hat I do everything in my power to ensure my son’s safety, even if it means setting aside high-minded principles. The long-term sequelae of infection in kids (“long-haul COVID”) is unknown and voluntarily leaving him exposed presents an ethical conundrum. As his parent I have also observed that making toddlers wear masks is particularly disruptive at a vulnerable stage of development where children are just learning to read peers’ social cues. Foregoing vaccine with the reasoning that kids can just continue wearing masks at school under-recognizes those developmental costs. And of course there is the issue of herd immunity. Kids have not been the community superspreaders for COVID-19 to the same extent as flu, but they still transmit (particularly for more transmissible delta variants) and the more unvaccinated kids there are in America the longer it will take for the country to fully reopen and normalize.

Washington Post op-ed from May 12, 2021

Mixed messaging around kids, COVID-19 risk, and vaccines will reduce rates of vaccination in kids and waste precious vaccine doses. My prediction is that America will get the worst scenario possible. No politician has the nerve to tell his constituency that American kids are being bypassed for vaccine to save people in other countries. But the mixed messaging from reputable scientific sources is going to scare parents and reduce vaccine uptake in kids under 12. The end result will be large volumes of wasted doses, continued mask-wearing in schools, not reaching herd immunity thresholds in most communities, and ongoing outbreaks. Score one for the Yanks!

How to Weigh COVID-19 Risks in a Brave New (Vaccinated) World

TL;DR: Everything is in place for the COVID-19 pandemic to end in America. The vaccines are working beautifully, even against new variants. But vaccine hesitancy remains a stubborn barrier to full normalcy, putting American on course to reach equilibrium, not eradication.

Ahead of last summer I was telling everyone they were fools for declaring the pandemic over and reopening too soon. Not this time. Unless new variants emerge that reduce vaccine effectiveness, the US trajectory is in good shape to continue a steady process of normalization. I’m bullish about the future.

The mRNA vaccines are rockstars. The data just gets better and better for the mRNA vaccines (Moderna and Pfizer). In a large study of breakthrough infections in vaccinated healthcare workers, only 1% got infected after one dose, and only 0.05% got infected after two doses*. The vaccines perform well against variants. No vaccine for any disease manages to protect everyone, but the COVID vaccines are similarly effective as the smallpox vaccine, which managed to eradicate the disease not just from America, but from the entire planet. In theory, if we could vaccinate enough people, we could eradicate SARS-CoV-2 not just from America but from the entire world, and never have to think about it again.

We won’t even reach herd immunity in America. For reasons that I explained last year, plenty of America is simply not interested in taking the COVID-19 vaccine, even with bribery. We all have friends and family who have explained to us why they are not getting vaccinated. Vaccine hesitancy is likely to be even stronger for kids. My son will get vaccinated as soon as it is available for his 2-year old age group, barring any new questionable data coming out of ongoing clinical trials. But a lot of parents are going to want to wait and see. I doubt school administrators will have the spine to require COVID vaccination for public schoolchildren the way they do for vaccines for other diseases like measles, mumps, rotavirus, and chickenpox. This could delay a return to normalcy for kids at school and potentially extend the wearing of masks and elements of social distancing. It is a tragedy that children continue to be the ones paying the biggest price for the mistakes of adults in mishandling the pandemic response and forgoing vaccination.

Kids do not need to wear masks playing outdoors. Given the delay in vaccine availability for young of schoolchildren, we need to begin seriously weighing risks of disease against normal freedoms to be kids. The time has come for kids to stop wearing masks when they play outdoors. The risk of COVID transmission is so low in outdoor settings AND kids are at low risk for symptomatic COVID infections. We have to get over our natural tendency to err on the side of maximum caution with children. It could be another six months or more before COVID vaccines are available for all kids over two. For those of us who live in Washington, DC where July humidity makes it suffocating to breathe under normal conditions, we cannot keep children bubble wrapped out of an undue abundance of parental caution.

As context, there were 279 reported COVID-19 deaths in US kids over the last year (5/21/20-5/20/21). Most were in teenagers.

Keep wearing masks indoors in public places even if vaccinated. No, vaccine was not the get-out-of-jail-free card some expected. You still have to wear a mask when you buy your groceries, ride public transit, go to work, or take your dog to the vet. It’s not a bait and switch, it’s just that practically speaking businesses have no way to tell who is vaccinated or not and have no option other than to enforce mask wearing among everyone that comes through the door. This is the reality: as long as large swathes of the country’s adults remain unvaccinated business owners have no other choice.

What happens if we do not reach herd immunity? Strictly speaking, herd immunity is a number. But population immunity operates on a spectrum. Even if America does not meet the magical herd immunity threshold that will completely eradicate COVID within our borders, each additional person who is vaccinated helps cut off possible paths of COVID transmission and brings community cases down. Already we can see the impact of vaccination on the rapid fall of COVID cases nationwide, resulting in fewer opportunities for transmission to the individuals who remain vulnerable. We may never vaccinate enough people to exterminate COVID, but we can aim for an equilibrium where the virus percolates at such low levels that most American life is unaffected and spontaneous outbreaks are rapidly dealt with. Getting vaccinated is not just about protecting yourself, but the entire community. Americans who decide whether to get vaccinated based purely on cost-benefits to themselves are either missing the big picture or don’t particularly care for their neighbors.

Technically this is not showing ‘herd immunity’, which is the precise threshold at which a high enough proportion of people are immunized (yellow people in the left column) that there are zero infected people (red people in the right column). But the general concept here is that vaccinated people serve as firewalls that block transmission within a community so fewer people get sick.

Variants present a threat to unvaccinated people. New variants emerging globally transmit at high rates, exploiting pockets of low vaccination. This has been evident in the UK where the India B.1.617.2 variant is currently exploding despite vaccination driving down cases of the previously circulating lineage B.1.1.7. This new epidemic is being driven by unvaccinated people and could threaten the country’s return to normalcy. The India variant has only begun to reach the US, but it has the potential to similarly exploit pockets with unvaccinated people.

Courtesy John Burn-Murdoch
https://twitter.com/jburnmurdoch/status/1397995388267810818

Are there any activities vaccinated people should still avoid? The risk of breakthrough infection is so low (particularly for the 2-dose vaccines) that the path to normalization for vaccinated people is really a matter of personal comfort. That said, as the country begins to normalize there is a need to be respectful of friends and family re-socializing at different rates. Some vaccinated people will be ready to party like it’s 1999 and others will barely change their lifestyle. Neither group is crazy. We’re entering a new phase where the most important act of social responsibility is simply to get vaccinated. What people do after that is largely up to their own weighting of personal risk and proclivities. I happen to be an outdoors person who is in no hurry to return to indoor dining, museums, cinema, or shopping malls. Even if I know the risk of breakthrough infection is small, I know that the CDC is primarily tracking breakthroughs associated with hospitalizations and deaths. I’m acutely aware that a ‘mild’ COVID infection is still nothing to trivialize. The other day I ran with a friend who had a mild COVID infection six months ago and still is struggling to run normally. It is unknown how long it will take for lung function to recover. I derive so much happiness from outdoor activities that I am more than willing to forego most indoor exposures to eliminate even a small risk. But I openly accepted that others whose enjoyment derives from indoor sources will make entirely different risk calculations that better suit their proclivities. Given the natural variability in risk tolerances, it is best to ask direct questions, explicitly request permissions, and avoid assumptions. Can I get a hug? Have you been vaccinated? Just for the record, asking colleagues, associates, or friends about vaccination status is not an invasion of privacy or protected by HIPAA. It is a valid question in a society experiencing a deadly pandemic for which there are strictly different protocols for vaccinated and non-vaccinated persons.

There is still plenty of COVID-19 going around (Pennsylvania shown here, for example), more daily cases than during the first wave last April. The pandemic is not ‘over’.

When can I hold my 200-person indoor wedding? It is not crazy to expect life to continue to improve and normalize as more Americans get vaccinated and COVID levels recede. I encourage vaccinated people to be bullish about planning events and travel. At the same time, there is a need to be realistic. The path to normalcy is underway, but without reaching herd immunity there will be no flip of the switch. COVID will still be around in 2022 and lots of people will still be unvaccinated. Even if I am personally vaccinated, along with my family, would I invite 200 people of unknown vaccination status to a densely packed indoor event? How confident would I be that enough people would be vaccinated to prevent a superspreading event? Will the city even permit an indoor event that size? How much COVID will be circulating at that time? Would I be uncomfortable mixing unvaccinated guests from across the country with my elderly relatives who may not respond to vaccine as well? Will antibodies from vaccine have waned by next spring? Would it not be better to hold the event outdoors so the bride has one less thing to worry about?

What about the rest of the world? The world is being divided into tiers of rich countries with access to vaccine and many countries, rich and poor, without access to vaccine. While the top tier speeds towards normalcy, the lower tier burns. Even Japan is not on track to host the Summer Olympics in Tokyo. I cannot emphasize how important it is to get vaccine to every country as fast as possible. That is why it is doubly infuriating that millions of Americans are foregoing vaccines and precious doses are increasingly going to waste. If we could get America to herd immunity quickly we could turn our attention to other countries in need of supply. The longer Americans stubbornly hold out, the longer it will be before we can get vaccine to countries that desperately need it.

* These data should be interpreted within the context that a lot of COVID was circulating at the time of the study, but on the other hand this was a young population that tends to mount a strong antibody response following vaccination and less prone to breakthroughs.

Why We Will Never Know the Real Origins of SARS-CoV-2

COVID-19 slashed red tape and poured in government funding to spark giant leaps forward in scientific innovation, most prominently in vaccinology but also behind-the-scenes in genetic sequencing to track a fast-evolving virus generating new variants. These developments set the stage for promising new strategies for a range of infectious disease threats, from malaria to influenza. In contrast, it should be lost on no one what minuscule progress has been made in figuring where the virus came from in the first place — and why.

Decades from now, when we sit the dinner table, regaling our grandchildren with sordid tales of the great Pandemic of 2020, we will recount the fear of touching doorknobs, the great run on toilet paper, and finally the joy of receiving the miracle vaccine that saved everyone and let kids go back to classrooms. But when our descendants ask where the virus came from and how it got into people, we will just have to take a long, slow swig of beer and admit that some things, like who shot JFK, are just never known.

We will list the various theories that got batted around, filling the airwaves with media fodder. Pangolin soup. Lab accidents in Wuhan. In contrast to other unsolved mysteries of science – why did the dinosaurs vanish? – the absence of a proven COVID-19 origins story presents a real practical problem going forward. The next pandemic virus is already out there, somewhere, circulating in an animal. The next global pandemic could blow in twenty years, or twenty months. Any global strategy for preventing future pandemics hinges on knowing whether to invest in shoring up lab vulnerabilities worldwide or massively expanding disease surveillance of ‘viral chatter’, which refers to the thousands of viruses that pass between animals and humans every year but in most cases never establish in humans. The absence of a resolved origins story saps the political will to do either.

As a scientist with a decade of experience studying how pathogens transmit between animals and humans I have a strong hunch about where SARS-CoV-2 came from, at least in principle. Strong enough to bet my career on. But science is not about hunches, and there is no point dissecting the conjectures, coincidences, and scraps of evidence that provide little more than tea leaves at the moment.

Tragically, it need not be this way. Conspiracy theories about global pandemics caused by scientists mishandling pathogens rise and recede every time an outbreak occurs, like a tide. When the 2009 H1N1 pandemic broke an Australian scientist propagated a theory that the virus contained genetic signatures that suggested it arose during an error in commercial production of influenza vaccines for US swine. A decade earlier, a Rolling Stone article outlined the evidence that HIV jumped to humans by way of a contaminated oral polio vaccine campaign in central Africa in the 1950s. The theory was researched in more detail in another journalist’s compelling 1000-page book. The page-turner was eloquent and a great read. The only problem: it was dead wrong. After a period of capturing the media’s attention, the theories were eventually put to rest by accruing scientific evidence.

It is a great deal easier to draw together a compelling lab origins theory based on conjectures and coincidences than it is to debunk one with hard scientific evidence. Tracking down the real source of HIV required arduous expeditions deep into Congolese jungles to sample viruses from apes. The team of Oxford researchers had to navigate rebel forces and swarms of mosquitoes (one famous professor died of malaria) during a needle-in-a-haystack search for simian viruses related to HIV. The search for the origins of the 2009 H1N1 pandemic in Mexico’s swine herds was tame by comparison. But my collaborators and I spent seven years painstakingly swabbing the noses of tens of thousands of pigs from farms to extract and sequence the genetic material of disease-causing pathogens to resolve the virus’s perplexing origins. An unusual amount of detective work was required to trace how swift globalization of swine farming in the 1990s led to pigs being moved across continents via commercial air travel that spread influenza viruses found in pigs in Europe, Asia, and the United States into Mexican farms, creating a new hotspot for influenza virus evolution and eventually a virus that could jump to humans.

The fact that the lab origins theories of the 2009 H1N1 pandemic and HIV did not hold up does not mean that human error never plays a role in disease outbreaks. One of my first scientific papers as a graduate student included genetic evidence that the 1977 H1N1 ‘Russian flu’ pandemic had been a lab escape (although it was not the focus of the paper). The H1N1 virus had circulated in humans from 1918 – 1957 before vanishing, only to surprisingly reappear twenty years later and cause a pandemic that mostly infected children, since most adults had already been infected when they were younger. The 1977 pandemic virus was nearly genetically identical to the virus that had circulated in the 1950s, a pattern that would not be seen if the virus had just been circulating in nature unobserved in humans or an animal reservoir.  Combined with knowledge that Soviets had been conducting experiments with a vaccine that included a live H1N1 virus that may not have been properly attenuated, we concluded that the 1977 pandemic was caused by human error and was a lab virus, which was supported by subsequent analyses. The lab-escaped virus caused recurring epidemics worldwide for forty years before it vanished a second time, replaced by a newer strain during the 2009 pandemic.

Despite technological revolutions in disease surveillance driven by advances in genomic sequencing and mobile phones, it is possible that we will know even less about the origins of SARS-CoV-2 than we know about influenza pandemics that occurred 10-40 years ago, or even a HIV pandemic that began a century ago. It is obviously not a a question of scientific capacity, but of access to samples. And not just samples from the Huanan Seafood Market where the pandemic was first detected in humans. The lack of SARS-CoV-2 virus detected in animals at the seafood market has been cited as evidence for a lab leak, but the argument is specious. The market is not where the original animal-to-human transfer occurred. The market merely amplified transmission in humans because many people congregate there, providing easy routes of human-to-human transmission. Certainly, a wet market presents an environment that is conducive to zoonotic transmission because humans and densely packed animals intermingle. But the first human case of SARS-CoV-2 was detected weeks before the major Huanan market outbreak. The original jump from animals to humans likely occurred 1-2 months before the Wuhan outbreak. Sampling from animals from a larger swathe of China would be helpful in piecing together where the virus traveled prior to the Wuhan explosion.

There is a long history of sensitivity about specific countries being blamed for pandemic pathogens that emerged within their borders. For that reason the 2009 H1N1 pandemic was termed ‘Swine Flu’ instead of ‘Mexican Flu’, breaking a centuries-old tradition of naming ‘Spanish Flu’, ‘Russian Flu’, and ‘Hong Kong Flu’ after the locations of origin (although there was equal backlash from swine farmers after a panicking public stopped buying bacon). During COVID-19 there has also been resistance against naming variants after the country where they are first detected (e.g., South Africa variant, India variant), which disincentivizes countries from performing rigorous surveillance so another country detects the variant earlier. Early references to the COVID-19 pandemic as ‘China flu’ had the same scapegoating effect that incentivizes plausible deniability when it comes to whether the pandemic originated in a specific country. Heroically brave Chinese scientists released early SARS-CoV-2 genome data in January 2020 to alert the international community when the pandemic was rapidly unfolding and authorities were still scrambling. The Chinese government is no longer on its heels.

Chinese authorities seized control of the COVID-19 outbreak in a way no Western government could, extinguishing the spiraling epidemic with a lockdown of fabled intensity. By February 2020, just as the Wuhan outbreak was winding down, the Chinese government turned its attention to the practice of farming of wildlife for food. Farming exotic wildlife had been promoted by the government for decades to advance the economy of the country’s southern rural regions. In a single edict the authorities wiped out the $70 billion industry and transferred the 14 million employees to new ventures. The destruction of all wildlife on the farms eliminated the potential for pathogen exchange between animals and humans that could spawn future pandemics. Tangentially, it also eliminated an entire vast ecosystem of hosts and pathogens that might have left a valuable paper trail of clues into the origins of SARS-CoV-2. Modern methods of genetic analysis can powerfully reconstruct decades of transmission and evolutionary events in the past from present-day data, as shown by our studies of pandemic H1N1 evolving on Mexican swine farms using data collected 4-5 years following the pandemic. There is no need for a time machine, but there is a need for live animals to sample. The lack of answers about SARS-CoV-2’s origins is no shortcoming of science, only a lack of access to samples in an age where it can be politically expedient to leave some scientific questions unanswered. It is clear by now that China answers to no one on the international stage.  

Agnosticism on the question of where SARS-CoV-2 came from seems logical in the absence of irrefutable scientific evidence to the contrary. But the overwhelming human predilection towards lab origins stories, as observed repeatedly over the history of pathogen outbreaks, particularly for HIV but also for the 2009 H1N1 pandemic, makes pure agnosticism a fiction. It is worth pointing out the enormous public health costs when people believe false lab origins theories. The contaminated oral polio vaccine theory for HIV set back the global campaign to eradicate polio by decades. America is at a juncture where the country desperately needs to shore up confidence in the COVID-19 vaccine, particularly as the campaign expands to younger children. The COVID-19 lab origins theory may seem unconnected to vaccine uptake, but it’s not. They all trace to a deep-rooted fear of government cover-ups, corruption, and arrogant scientists who ignore risks and take advantage of people’s blind trust. Being agnostic on the origins of COVID-19 may seem innocuous, but it’s not. I wish I had the data to prove otherwise. Sadly, I don’t think I ever will. And I dread the day I have to explain that to my grandchildren.

The Smoking Bat: The Quest To Uncover the Origins of SARS-CoV-2

The World Health Organization’s recent probe into the origins of COVID-19 in Wuhan has renewed interest in piecing together when, where, and how the virus jumped from animals to humans during the fall of 2019. The Wuhan Seafood Market outbreak appears to be a red herring, serving as an early amplifier of a simmering outbreak in December 2019, but not the original source of the animal virus, which jumped to humans weeks, or possibly months, earlier (1). The pangolin’s brief moment of fame also appears to have been a red herring, as the pangolin viruses were only distantly related to the human viruses (2). Then again, we know previous little about coronavirus diversity in pangolins and other species. As attention focuses on the first human cases in China, including the unreleased raw data, there has been a notable lack of public interest in what the virus was doing before its grand entrance in humans and how little coronavirus data is available from animals.

Contagion got many things right about outbreak investigations, but the film oversimplified how scientists trace a pandemic’s origins back to animals. At no time in history has an outbreak’s zoonotic source been solved using security camera footage. Anyone who has searched for the animal origins of Ebola outbreaks in bats in West Africa knows how painstakingly laborious the task of sampling wildlife is. Theoretically livestock are easier because at least we know where they are housed. But the politics of getting access to samples can be equally daunting when a wrong bug found in a herd could cost a farmer their lifesavings.

But as humans grapple with the current COVID-19 crisis, the ancestor of the next pandemic virus is already lurking in an animal host somewhere. It could be in a bat in China, a primate in sub-Saharan Africa, or a pig in the Americas. The virus could be a decade away from acquiring the properties needed to transmit to humans, or it could be weeks. Despite the disruptions caused by COVID-19, humans continue to create conditions for zoonotic transfer of viruses from animals to humans, consuming millions of animals every day, congregating in live animal markets, and even holding pig shows. Imagine another pandemic on top of COVID-19.

How can we learn more about a zoonotic event that occurred over a year ago? For approximately the same price tag as what the UK government is currently investing to characterize several thousand SARS-CoV-2 viruses a week (3), researchers could at least begin a sweeping survey of the genetic composition of hundreds of thousands of coronaviruses circulating in wildlife, livestock, and live animal markets across east Asia. A region-wide survey conducted a year following the original animal-to-human transmission event is not guaranteed to produce the ‘smoking gun’ virus or pinpoint which market or farm was responsible. But the descendants of the virus that jumped to humans continue to circulate in animals in China and other Asian countries, and the genetic material of each virus provides important clues about its grandparents. Scientists can reconstruct decades of evolutionary history from gene sequence alone.

Mexico’s response to the 2009 H1N1 influenza pandemic proves how decoding viruses in animals even years after the event can resolve the mysteries of a pandemic’s origins and provide the global community clues for how to prevent the next one. At first, scientists thought the virus that caused the global pandemic in 2009 came from pigs in China, where the most closely related animal flu viruses were found (4). China seemed a logical source, given that the last two influenza pandemics originated in China and the country is home to half of the world’s pigs. Although the first signs of the virus transmitting in humans occurred in Mexico (5), Mexican pigs seemed like an unlikely source because the virus contained genetic material that had never been seen in pigs in any country in the Americas. For seven years it remained a mystery how a virus that seemed to come from Chinese pigs presumably sparked its first human outbreak in Mexico. Had Chinese pigs been smuggled into Mexico? Or had Chinese pig farmers vacationed in Cancun just after acquiring the virus?

Imports of live hogs into Mexico
(Mena I, et al., 2016)

To its credit, Mexico resolved the mystery by embarking after the pandemic on new surveillance of influenza in its swine herds scattered across the northern, central, and far eastern regions of the country. By working with Mexican swine veterinarians our research team uncovered a surprising find: viruses similar in important ways to those in Chinese pigs (6). The story told how Mexico’s rapid modernization of swine production in the 1990s allowed viruses from different continents to be imported and hybridize with each other to create a pandemic in a country assumed to be low risk. While swine farmers care a great deal about keeping deadly pathogens like African swine fever from crossing borders, influenza is already in pigs in every country and newly imported strains are not perceived as a problem worthy of testing or quarantine from an animal health perspective.

Altering food production is economically costly and socially disruptive. Just as COVID-19 lockdowns have become less blunt as key vectors of community transmission were identified, changing how we operate live animal markets, wild animal trade, or bushmeat needs to be grounded in data. Two centuries ago, the grandfather of modern epidemiology John Snow was successful because he used rigorously collected data to pinpoint a single contaminated water pump that was causing the bulk of cholera deaths, and did not ask authorities to disengage every pump in the city. But scientists need a great deal more data to track disease transmission in animals at anything approaching the levels we achieve in humans. We can uncover how coronaviruses get shuttled between countries and continents by trade of wildlife and livestock, as well as by movements of wildlife displaced by habitat loss, and how this relates to human coronavirus outbreaks. Although viruses similar to SARS-CoV-1 in 2003 were identified in civet cats in a live animal market in China (7), we do not know how those viruses wound up in civets in the first place. Are pangolins or other traded wildlife species an important permanent reservoir for coronaviruses connected to human outbreaks? Where did the four coronaviruses that cause common colds in humans come from? Again, the limiting factor is data.

How viruses get shuttled between species and continents. Phylogenetic trees show how influenza viruses sampled from different types of animals and countries are related. We worked with small animal veterinarians in China to show how viruses jump between birds, dogs, and cats and moved from Asia to the US (8)

With over two million COVID-19 deaths it may seem pointless to figure out where the virus came from originally. But fundamental insights into disease systems can have impacts far beyond a single disease event. Although John Snow only asked authorities to turn off a single water pump, the insight that cholera epidemics might be vanquished by cleaning up water supplies transformed the 19th century. The construction of modern sewer systems turned the Industrial Revolution’s squalid, disease-ridden cities in Europe and America into modern economic centers capable of supporting skyrocketing densities. Some day we may back look at the dark ages of 2020 with the same curiosity as ‘night soil men’ pushing carts of human feces and horse dung down Broadway.

TL;DR. Half the world thinks SARS-CoV-2 came from a lab escape. The other half thinks someone ate a bat. Scientists can do a great deal better, and avert future pandemics, but they need data from animals.

References

  1. Pekar J, Worobey M, Moshiri N, Scheffler K, Wertheim JO. Timing the SARS-CoV-2 Index Case in Hubei Province. bioRxiv [Preprint]. 2020 Nov 24:2020.11.20.392126.
  2. Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, Tong YG, Shi YX, Ni XB, Liao YS, Li WJ, Jiang BG, Wei W, Yuan TT, Zheng K, Cui XM, Li J, Pei GQ, Qiang X, Cheung WY, Li LF, Sun FF, Qin S, Huang JC, Leung GM, Holmes EC, Hu YL, Guan Y, Cao WC. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature. 2020 Jul;583(7815):282-285. 
  3. Nelson MI. 2021. Tracking the UK SARS-CoV-2 outbreak. Science. 371(6530):680-681.
  4. Grantz KH, Meredith HR, Cummings DAT, Metcalf CJE, Grenfell BT, Giles JR, Mehta S, Solomon S, Labrique A, Kishore N, Buckee CO, Wesolowski A. The use of mobile phone data to inform analysis of COVID-19 pandemic epidemiology. Nat Commun. 2020 Sep 30;11(1):4961.
  5. Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, Miller MA. 2009. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med. 361(7):674-9.
  6. Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, Ma SK, Cheung CL, Raghwani J, Bhatt S, Peiris JS, Guan Y, Rambaut A. 2009. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 459 (7250): 1122-5.
  7. Mena I, Nelson MI, Quezada-Monroy F, Dutta J, Cortes-Fernández R, Lara-Puente JH, Castro-Peralta F, Cunha L, Trovao NS, Lozano-Dubernard B, Rambaut A, van Bakel H, García-Sastre A. 2016. Origins of the 2009 H1N1 influenza pandemic in swine in Mexico. eLife 5: e16777. 
  8. Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, Luo SW, Li PH, Zhang LJ, Guan YJ, Butt KM, Wong KL, Chan KW, Lim W, Shortridge KF, Yuen KY, Peiris JS, Poon LL. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003 Oct 10;302(5643):276-8. 
  9. Chen Y, Trovão NS, Wang G, Zhao W, He P, Zhou H, Mo Y, Wei Z, Ouyang K, Huang W, García-Sastre A, Nelson MI. Emergence and Evolution of Novel Reassortant Influenza A Viruses in Canines in Southern China. mBio. 2018 Jun 5;9(3):e00909-18

Mutants on the Rise

TL;DR: New variants cropping up globally are headed to America and threaten to overwhelm hospitals. Our highly potent vaccines still protect pretty well against new strains, but we are not rolling out vaccine fast enough to prevent new epidemic spikes.

November’s announcement of highly effective COVID-19 vaccines brought a refreshing break in the otherwise bleak pandemic news cycle. New threats are on the rise, however, as a new contagious UK variant has already made landfall in a dozen US states and could soon lead to new epidemic spikes and overcrowded hospitals. The Brazil and South Africa variants could evade some immune defenses and are headed our way as well. Allowing virus populations to explode globally opened the door to evolution. Each of the 100 million confirmed global COVID-19 cases provides another opportunity for the virus to grow and morph into deadlier, more transmissible forms. Bullets are deadly, but at least they do not use each victim as a personal petri dish.

Fortunately, all is not lost. The COVID-19 vaccines were so good to begin with, inducing such a broad antibody response, they can still protect against a variant capable of evading a certain subset of antibodies. So please tell your grandmother to keep hammering her local vaccination registration page, no matter how many times it loses her data. With mass vaccination still the only option for achieving herd immunity, perhaps by mid-2021, the last thing we need is another news cycle fanning America’s enormous problem with vaccine hesitancy.

As you roll up your sleeve for the syringe, be aware that the COVID-19 vaccine is designed to elicit a large, broad immune response potent enough to protect old people with weak immune systems. In the interest of speeding through clinical trials and vaccine distribution, different formulations were not tested for seniors versus young adults, as they are for influenza jabs. As a result, some young adults may have unusually strong immune responses to the vaccine, particularly to their second dose or if they were naturally infected with COVID-19 previously. Most people will have no reactions to the vaccine, but for those who get a fever or a goose egg-sized swelling on their arm, I’m afraid it is simply the price of admission for protection against the deadliest pandemic in over a century. As more variants emerge that evade certain antibodies, we will be grateful that these potent vaccines activate multiple lines of defense.

Note that more people reported muscle pain who received the placebo (vertical black line) than the Moderna vaccine. People get surprised by new medical problems all the time. As millions (billions!) more people get the COVID-19 vaccines, expect an untick in the number of odd strokes, seizures, and deaths that occur right after vaccination by chance. Merely a coincidence of timing in a giant numbers game. Responsible media will not report such events before scientists have time to figure out if they are related to the vaccine or not. Clickbait media will.

Minor vaccine reactions can be a good sign. I exclaimed Perfect! in response to my son’s three days of snotty nose and malaise after receiving a FluMist vaccine I fought to get this winter instead of the intramuscular version. There are are no clinical studies showing that a two-year old going a year without major immune system challenges because of pandemic isolation is damaging. Just intuition from a evolutionary biologist who did not have to wait for pediatricians to finally update their disastrous advice on early exposure to peanuts.

There is still a lot of uncertainty about these variants, including whether they cause more severe disease in people who get infected and how well they evade detection by the body’s immune defenses. Preliminary data from South Africa indicates that its variant can evade certain antibodies elicited by vaccines, reducing their effectiveness. The UK variant (B.1.1.7) appears to transmit more efficiently between people and has quickly become the dominant virus in the UK and is causing epidemics so severe they must ration oxygen in hospitals. The UK variant has already made landfall in a dozen US states and is will likely become the dominant virus in a matter of months, depending on the particular city or state. High vaccination rates in nursing homes and other vulnerable populations can blunt the mortality rates of epidemic spikes, but as of now we have only vaccinated 17% of the prioritized population. That still leaves a lot of vulnerable people, including those with medical conditions who are not currently in the vaccine queue. COVID-19 cases are beginning to come down after the holiday surge in most states, but a more contagious virus is exactly the kind of tinder on the fire America does not need as it tries to reopen schools. After keeping UK schools open all fall, the variant forced classrooms to shutter again.

Buss et al., Science (2021): Three-quarters of residents in Manaus, Brazil have antibodies to SARS-CoV-2 viruses by October 2020

Why are variants suddenly emerging now? This is all highly speculative, but it may not be a coincidence that South Africa had one of the highest attack rates during the first wave of the pandemic. People with residual immunity from a first infection may now be getting second infections. When a person gets infected a second time, the virus is attacked with primed antibodies, exerting new Darwinian selection pressure on the virus to evolve as a matter of survival. The emergence of a new variant in Brazil could also relate to the extremely high attack rates in the Amazonian city of Manaus, where an uncontrolled virus swept through three-quarters of the population earlier in 2020. Virus evolution may seem random and unexpected, but it is encouraged by human activities. One way to spur the virus to evolve is during repeated treatments of long-term chronic infections in patients with weakened immune systems who are unable to clear the virus. Frankly, if you wanted to design an experiment to spur the virus to evolve, bombarding the virus with one antibody cocktail after another would be a good way to go about it.

Viruses Evolve A Million Times Faster Than Humans. This is the problem: Every time a SARS-CoV-2 virus infects person it replicates. What begins as a family of virus particles in your body explodes into a swarm of viruses, which includes thousands of clones and as well as variants that have new mutations and are slightly different. Since the SARS-CoV-2 virus was already superb at infecting and transmitting between human bodies, most tweaks in its offspring will not be particularly helpful and those mutants will die off. The virus has so many offspring, it can afford to lose most of them, like a kamikaze army. But every now and then, one of the offspring will have a special change that actually makes the virus fitter. Maybe the virus attaches to human cells better. Maybe it escapes cells better to infect more cells. There are a dozen or more steps a virus has to accomplish to successfully invade a human body, replicate en mass, and invade another person. An improvement at any one of those steps makes will make a virus fitter than its brethren.

Evolution is Hard Even For Viruses. In theory, these kamikaze armies of viruses should be evolving like gangbusters. But it’s more complicated than that. Imagine you’re a virus, spreading like wildfire in your poor human’s body, replicating quickly, and you manage to hit the jackpot and one of your offspring lands on a helpful mutation. The problem is that most of the virus swarm does not have a roundtrip ticket. Only a relatively small proportion of offspring will spring from the upper airways to a second unwitting host. Another problem is called epistasis, which is really just a fancy word for bad baggage. Mammals take great care to replicate their DNA with fidelity to avoid costly errors. Even creatures as prolific as rabbits don’t want grotesque mutated offspring and have protein machinery to check for errors in DNA replication. With thousands of progeny, viruses don’t care if some turn out to be the equivalent of a three-headed rabbit. But such levels of sloppiness carry a cost. A good mutation can occur in one of the viruses in the swarm that happens to have a second unhelpful mutation, say the equivalent of the three-headed rabbit mutation. Since beneficial mutations are extremely rare and most mutations make life worse for the virus, it can be difficult to land a good mutation in a problem-free genetic background. Good mutations can get taken down by a faulty ship.

Evolution in one direction incurs tradeoffs in other ways. Just ask the giraffe trying to awkwardly bend down to drink from a river. Coronavirus evolution also incurs tradeoffs. Jailbreaking into human cells is not easy and requires fine-tuned configurations of the virus’s spike protein to attach to cell receptors. Spike proteins that jut out of the virus also happens to be the target of most human antibodies. So the same spike protein mutations that help the virus evade antibodies could impede cell attachment and other functions. The virus may need a second mutation to compensate. Evolution is not necessarily easy for a coronavirus, but we encourage it by creating enormous virus populations across the globe, letting viruses blast through specific populations to create pockets with higher selective pressures, and administer series of therapies to chronically infected patients, creating human petri dishes for evolution. Human cannot necessarily predict how or when the virus will evolve, but we have a degree of control over the conditions that drive it.

Going forward, making a vaccine is a giant leap forward, but there are still hurdles. Vaccine distribution and hesitancy are two big ones. Attaining herd immunity assumes that the vaccine not only protects against illness but also reduces virus shedding and transmission, which is likely but still being assessed. And the virus is a moving target, particularly when we give it plenty of runway and incentive to evolve. The emergence of new variants is also a wakeup call to the global community that we are in this mess together. We can theoretically vaccinate the entire US population, but vaccine escape variants can still emerge in other parts of the world where the virus is not controlled. Funding vaccine efforts in developing countries is not only ethical but in our self-interest.

The take-home message is that viral evolution has constraints, and coronavirus is not going to suddenly turn into Ebola. Still, three new variants serve as a reminder that the SARS-CoV-2 virus capitalizes on our past blunders and is not going gently into the night.

Can Americans Win at Game Theory?

From childhood, I was determined not to become an economist. My father was an economics professor. So was his father, sister, and brother-in-law. I don’t know what other families talk about at the dinner table. My family talked about airline deregulation. My father was conservative, his relatives were liberal, and the same circular arguments about private sector versus government-led policies fell along predictable partisan lines with no one ever convincing the other of anything. Resolution was not the point. It was just politics for sport.

I rebelled and became a scientist, a novel career choice among five generations of Wechslers, Daums, Nelsons, and Palonens. RNA viruses had nothing to do with politics. I studied the genetic code of microbes found in humans and animals around the world to figure out how pandemics arise. On occasion when my father tried to rope my scientific opinion into a family debate on climate change, I would wander off into another room to find a cat willing to be pet.

Then in January 2020 the COVID-19 pandemic began. I tried for nine months to stick to science and medicine. But I found myself unable to fully explain America’s COVID situation without drawing on economics. Because as the COVID-19 pandemic wears on, America has become trapped in a very real prisoner’s dilemma. Until all Americans understand how the game works, everyone loses.

For those uninitiated with game theory, the prisoner’s dilemma is a situation in which individuals have an incentive to make a choice that does not produce the optimal result for the group.

Two members of a criminal gang are arrested and imprisoned. They cannot communicate. The authorities cannot convict them on the main charge (20 years jail time), but they can on a minor charge (6 months jail time). If they both stay silent they get they both get the lesser 6 month sentence charge, the optimal result between the two of them. 

But, if one speaks out then that person is released, and the other person is put away for 20 years. The incentive is for both to betray the other, in the hope of getting a reduced sentence, but which results in them both getting a medium sentence (8 years jail time). The implication is that two individuals acting in their own interest reach a suboptimal outcome.

Suboptimal outcomes occur all the time because individuals and countries are prone to acting in what appears to be self-interest, whether in missile defense, NASCAR racing, auction bidding, or in business. Cooperation can halt arms races and achieve the most optimal outcome for all, but requires international treaties, state laws, or industry-wide agreements that create rules or systems that incentivize cooperative behaviors.

For example, a fisherman has an incentive to harvest as many tuna as possible each year. But if every fisherman overfishes, the entire stock becomes depleted and everyone loses money in subsequent years. Instead, if every fisherman agrees to limit their annual catch, the tuna population thrives and everyone earns more money in the long run. A collective strategy is needed, either by industry self-regulating or by government setting catchment limits, to produce the highest earnings for everyone.

How is the COVID-19 pandemic an example of prisoner’s dilemma? Because most individuals do not have a high risk of dying. A young individual with no underlying health conditions could reasonably look at the odds of severe disease and conclude that they accept the risks and wish to host parties, attend rallies, forego face masks, and travel to visit family over the holidays.

But if everyone ignores recommendations by public health officials, COVID-19 transmission would quickly skyrocket, large numbers would die, including younger people, and businesses and schools that were previously open would need to close. Presenting COVID-19 as a personal choice and an exercise in individual risk assessment produces a sub-optimal result for everyone. A better strategy would be if everyone collectively, like the fishermen, agreed to incur a reasonable limit on their behavior, even if it is not immediately in their self-interest, with the understanding that it would produce a higher return for everyone, including themselves in the long run, by containing virus transmission below a certain level and sustaining a national economy.

Certainly there are barriers to implementing such a strategy in the real world. For one, how do you induce Americans to act towards an optimal outcome when scientific information has been misconstrued and there is no nationwide agreement on the scale of the pandemic threat to begin with? You can’t expect the actors in the prisoner’s dilemma to cooperate if they believe jails are just a hoax designed to scare people.

But even if the optimal outcome cannot be realistically achieved in today’s political climate, there is still value in understanding the concept of prisoner’s dilemma and why a ‘personal choice’ approach to COVID fails everyone. Principles of game theory help explain why families should not travel over the Thanksgiving holidays, even if they accept the personal health risks. Or why everyone can enjoy more freedoms, such as participating in outdoor running events or in-person kindergarten, if everyone cooperates and accepts a reasonable set of limitations, such as refraining from mass indoor gatherings, to keep the virus in check.

Because of superspreading events, 20% of COVID cases contribute to 80% of transmission events. As a result, a realistic approach to COVID control may not be convincing 50% of the population to lockdown stringently (>80% change in behavior), but instead convincing >95% of the population to change their behavior 30%, focusing on avoiding large gatherings (e.g., rallies, weddings, funerals, church, parties) that spark superspreading events. In the context of game theory it makes sense that all individuals accept limitations on behaviors associated with superspreading events, regardless of their personal risk tolerance for other activities, such as riding motorcycles, skydiving, or smoking.

Risks can be compared using “micromorts,” which measures a one-in-a-million chance of dying. The average American endures about one micromort of risk per day, or one in a million chance of dying from nonnatural causes. From March 15 to May 9, New Yorkers experienced roughly 50 additional micromorts of risk per day because of COVID-19. which translates to being 2x as likely to die as US servicemen in Afghanistan in the deadly year of 2010. Last spring Marylanders experienced the same risk as skydiving every day (7 micromorts per jump). These risks are aggregated over age groups and a more meaningful measure would be stratified by age.

A game theory framework does not require people to ignore individual risk altogether. Seniors and those with underlying conditions may opt to limit their exposure even more stringently. The key point is that individuals should not behave only according to their personal risk. A little knowledge of game theory could help people reconcile seemingly conflicting messages of COVID is a risk I’m willing to accept with But it is still in my interest to cooperate with reasonable public health recommendations.

Understanding how COVID relates to game theory also explains why face masks may be just as important for promoting societal cooperation as in reducing disease transmission. In a pure prisoner’s dilemma situation, the prisoners cannot communicate with each other or telegraph any intention to cooperate. However, in the real world people openly communicate their COVID decisions. Wearing face masks has become a powerful way for an individual to telegraph their adherence to public health guidance and reinforce cooperation across a community. Sustaining motivation to limit behavior can be difficult without ongoing reinforcement and confidence that others are also making similar sacrifices.

Admittedly, a face mask is not a perfect indicator of an individual’s COVID behavior. A person could wear a face mask in public and hold large transmission-friendly gatherings at home. But the face mask has become an important way to signal to community members that others are sacrificing for the greater good. I have to acknowledge that as a hard-numbered scientist I have focused on face masks purely from a disease transmission perspective. At times I have undervalued their societal importance in promoting cooperative behavior. As I said, I’m a scientist, not an economist. But I am accepting that it will take more than science to save America from COVID.

Understanding game theory may also help understand why America has more COVID deaths than any other country. Americans value a form of rugged individualism that is great for cinema and entrepreneurship, but a major disadvantage in controlling COVID. Globally, we have ongoing natural experiments in how countries with different cultures and governments succeed or fail against COVID. Countries that have successfully contained COVID tend to have deeper cultures of cooperation and deference to authority, such as Canada, Denmark, Rwanda, Singapore, South Korea, and China.

But game theory should give Americans hope. With the awful 2020 election finally in our rearview mirror, now is the time to reset. Right now many Americans, particularly conservative-leaning, still view COVID public health recommendations as intrusive and paternalistic. Public health officials focused on averting deaths still find themselves pitted against economists focused on preserving jobs and avoiding the costs of lockdowns. Public officials must offer a more coherent and persuasive strategy than media-inflamed fear tactics. We must find new ways to incentivize people to incur a degree of inconvenience and delayed gratification, even if it’s not in their immediate self-interest, because they understand why.

Another way to understand game theory involves jellybeans. Four people sit at a table with a bowl in the center and every minute the number of jellybeans in the bowl doubles. Anyone is free to take jellybeans from the bowl at any time. After a certain time period (which the players do not know) whoever has the most jellybeans wins. Doesn’t sound like a complicated game, right? But there are multiple conflicting incentives. Every time a person takes a jellybean they (a) incentivize others to take jellybeans and (b) reduce the total number of available jellybeans. Instead, if players all refrain from taking jellybeans while they double and double, then a huge number will start to overflow in the bowl that everyone can indulge in. Perhaps elected officials should have to play the jellybean game before they are allowed to take America out of international nuclear arms treaties.

The jellybean game is similar to COVID because both systems involve exponentially growing populations that require discipline early on, with reward coming later. Instead of refraining from jellybeans, if Americans could refrain from bars, parties, and other gatherings during early signs of the virus taking off in a community, everyone could indulge later. So how do we convince Americans to refrain from grabbing the jellybeans during that critical early window so they can feast later on? I don’t know. I’m tapped out. Ask a real social scientist.

A Marmot’s Survival Guide for the Fall of 2020 (i.e., it’s better to know if we’re screwed and plan for it)

Dear America,

By now, six months into the COVID pandemic, you’re probably ready to punch someone in the face. Maybe you lost your job. Maybe your local school district just told you they’re not offering in-person school this fall. What the bleep am I going to do with my children?? Maybe you’d like to sucker punch one those guys who still won’t wear masks at the grocery store. Or young people taking selfies at bars. Or just Floridians in general.

But this is not where your anger should be directed. Many people aren’t helping the COVID situation. But they’re not the crux of the problem. You know what you should really be angry about? Testing.

America’s testing capacity has greatly expanded since March. America currently produces more tests than any other country. We even have fun saliva tests you can ship from your home directly to the lab. But the volume of tests is not the most important measure of success. It’s speed.

This data is from March but the trend has persisted (Source: MIT Technology Review)

Atlanta Mayor Keisha Lance Bottoms was recently a victim of America’s Great Testing Failure. Bottoms had her entire family tested for COVID on June 29 as a precaution after attending the funeral for Rayshard Brooks, a 27-year-old African American man who was fatally shot by Atlanta Police Department (APD) officer Garrett Rolfe.

Mayor Bottoms consoles Tomika Miller, the wife of Rayshard Brooks, at his funeral in Ebenezer Baptist Church

A week later her test results still hadn’t come back. With her husband starting to feel ill the family went to Emory University to get a different rapid test. Within hours, Bottoms learned that she, her husband and one of her four children were positive.

The results from the initial test finally arrived the next day (8 days after the swabs were sent). They showed that when the family first got tested, only one child was positive. Either Bottoms and her husband had gotten false-negative results, which is possible if the funeral had been the source of the virus and the Bottoms family was tested too soon after exposure, when false-negatives are common. Or the child had possibly passed it to his parents while they waited for their test results.

Either way, this example shows how long delays in test results help spread COVID. During the week when Mayor Bottoms was waiting for her results she didn’t have any symptoms. So she followed a normal mayoral routine, including holding a press conference and meeting with staff, potentially infecting other people.

It’s also worth noting that even the mayor of one of America’s largest cities had difficulty figuring out how to get a quick test in America’s tangled network of private and public laboratories. FDA has authorized rapid tests that can give a COVID result in hours. But first you have to find a place that has them. And maybe pay out of pocket. Vault’s at-home saliva test costs $150. And even if you can find a test that produces a result quickly, you’re in the dark about whether that test performs well or gives high rates of false results.

Common message these days.

Ultimately, the longer the delays in test results, the longer asymptomatic people will be floating through society infecting other people. Which, by the way, happens to lead to more sick people, heavier demand on already stretched testing capacities, and, that’s right, even longer delays in testing. Welcome to the wonderful COVID Feedback Loop of Death!

Line for COVID testing in Portland

The problem is that testing is only worthwhile if it is actionable. Test, trace, isolate does work in other countries like South Korea where you get a test result back in a day. When someone in a family tests positive (a) that person is isolated from other family members to reduce household transmission, (b) the family as a unit stays home to minimize the risk of infecting others in the community, (c) other family members immediately get tested, and (d) other friends or coworkers that the index case may have had contact with get immediately informed so they can get tested and isolate until they get the test result back to protect their own family. None of those actions to stop COVID spread happen if it takes a week to get a result back.

You can see how an American society that takes 8+ days to get test results back either (a) grinds to halt economically because staff and business can’t go back to work until test results come back or (b) spreads a lot of COVID around because asymptomatically infected people won’t know they’re positive until they’ve already spent a week infecting other people. The longer it takes for test results to get back, the higher the risk of asymptomatic people spreading COVID to their families and the community.

My overall point is this: we are asking Americans to battle COVID with everything they got: masks, social distancing, isolation. But we are not giving them a fighting chance if we don’t have rapid testing available. We are not giving schools a fighting chance. Or daycares. Or restaurants. Or even MLB.

Americans are determined to get back to business this fall. To open colleges, go back to the office, send kids off to school, even have some NFL games. We’ve been told to just write plans. Major League Baseball’s COVID plan alone runs 101 pages. My son’s preschool’s plan includes a schedule of when three-year old classes can use their designated bathroom. Dammit Jimmy you’re going to have to hold it until 3pm. Right now is the grasshoppers’ shift. Anyone who’s not impressed by the grueling effort to develop COVID plans and the sheer commitment of staff to perform the impossible should see how far they get trying to get a two-year old to hold their bladder for more than ten minutes.

But we’ve already seen glimpses of how quickly plans derail when even a single positive case occurs within a poorly functioning COVID testing infrastructure. This is not complex math. A lot of COVID in the community + of lot of asymptomatic carriers means an organization is likely to experience sporadic positive cases. Most of these cases will be isolated and not spread to others in the organization. But the operation is paralyzed until test results come back for all the COVID case’s contacts. The longer the wait for the test results, the longer the other employees/staff/students are stranded at home in limbo. With test results taking up to 8 or more days to come back, you can imagine it doesn’t take a whole lot of cases before people are spending as much time waiting at home as on site. You can get around this to some degree by siloing groups and limiting contacts and the number of people that need to quarantine (hence the miraculous rotational bathroom schedule at my son’s preschool). But many buildings are simply not constructed in a way in which groups will never share space. Especially when you include the ventilation system.

So while we’ve laid the burden of planning for COVID squarely on individual businesses and local governments, someone should start the waving the white flag around and point out that all these plans are useless if there’s no larger plan to make testing available for those that need it and to shorten the turnaround time between test and result. Just a couple weeks in, even the MLB practice schedule has been derailed by testing delays.

It’s not entirely clear why there is no national plan to develop testing capacity. A dire need for more testing happens to be the only thing economists and epidemiologists can actually agree on. Testing helps open the economy and keep people safe. It should be a bipartisan slam dunk.

We even have the nifty Defense Production Act (DPA) that can be wielded to get American companies to direct their resources towards producing materials critical to national security. Reagents and testing materials would certainly qualify.

But we don’t just need a plan for how to make more tests. We need a plan for how to shorten the turnaround time and deliver results quicker. To get tests to areas with critical shortages. We need a defined pipeline of new rapid test development, similar to what we have for vaccines and therapeutics. And we need reliable tests. Dozens of different tests have been granted Emergency Use Authorizations (EUA) by FDA. Including an in-home saliva test you ship directly to a lab that promises 48-72 hour results. But EUAs are evaluated on a rolling basis of submitted data and many could turn out to be unreliable. It’s tough to tell a 60-year old teacher to risk their life by showing up to class every day if students with suspected COVID cases can’t get a test result back in within a day or so. Or if a negative result has a high probability of actually being positive.

We also need to recognize that even with the DPA tests are not an unlimited resource. I know baseball is important, but there are 750 players plus a large entourage of managers, medics and staff that are being tested every other day. While ordinary Americans sit in hours-long waits. I’m not saying baseball isn’t worth it. I’m just saying that people in a positions of power should be debating this and not leave questions of access to whoever has the deepest pockets.

Pooling tests sounds like a simple way to improve efficiency. But that approach only works efficiently at lower levels of COVID positivity.

How hard would it be to develop a national plan for COVID testing? Well, a simple start would be to reappoint someone as the national testing czar, a position that was disbanded during earlier this summer. Remember that honeymoon period in May when everyone thought COVID had been kicked? Someone didn’t get the memo that the honeymoon is over.

But testing is an enormous logistical challenge that is beyond the capacity of any single czar. I certainly don’t fancy that improving testing is easy. But we haven’t really tried. We don’t have a testing task force. Or clearly stated goals. For not just the quantity of tests, but turnaround time, a robust pipeline of new tests in development, and rapid analysis of data to quickly determine which tests are crap and should be pulled from the market and which have promise and should be scaled up in production. Poor FDA was overstretched and underfunded even before COVID. And expect testing capacity to become even more strained in autumn and winter when cold and flu seasons begin and doctors need to distinguish COVID from other suspected respiratory virus infections.

Ultimately, what does it mean that we have no national testing plan? It means that all those plans written for schools and businesses are in a tight spot. Their success clings to the hope that COVID levels are so low in the community that they won’t have to deal with many positive cases. Maybe in Vermont. Not in Miami.

And in the end that means that a lot of places in America are going to need to brace for a rough fall. Because their plans have deep vulnerabilities that have nothing to do with a teacher’s ability to enforce pediatric bladder control. If you live in a place where COVID is still circulating uncontrolled in the community it is not too soon to start thinking about contingency plans for when schools close. Or daycares shutter. Or flights cancel. Or universities send kids home. Won’t it be fun to relive all those fun nostalgic memories from March 2020? Although six months into the pandemic it will be less scary and more infuriating. Because we had so much runway to get our act together. And just totally dropped the ball on the single most important thing.

Given this reality, how can a practical person try to prepare? First, if you’re a parent living in a state with rising COVID cases and low testing capacity, you should consider the real possibility that in-person schooling will shut down again this fall. Some large school districts have already announced that they’re not offering in-person education this fall. I have no perfect solutions for America’s impending wave of societal upheaval. But here’s my best advice: band together. Young children aren’t going to obediently follow online education for six hours a day. And parents need to get some work done. Consider creating pods of 2-3 families that are well-matched in the ages of their children that can have a rotation of designated parents across the week to supervise a mix of in-person and online learning.

Sure, this introduces a level of COVID risk. It’s accepting another family or two into your circle of trust. And it could be hard to find a family that is matched in terms of kids’ ability to sit still plus parents’ ability to supervise learning. Not to mention finding a family with similar thinking about masks, hygiene, etc. But we need to craft new systems and makeshift markets. Try outdoor education to minimize COVID risk. Maybe one parent focuses on music, another on outdoor play, another on history. Maybe one parent ends up doing more supervision than others and gets compensated financially for their time. We’re in the middle of a global catastrophe, so try to be flexible and keep the expectations low. A round of Haagen-dazs if the kids happen to learn anything.

TL;DR: America has made more COVID tests than any other country. But until we cut down the time it takes to get a test result our plans for opening schools, offices, and even baseball are threatened.

Primer on COVID Testing

PCR (virus detection): For people who think they have an active infection. Tests for virus genetic material in nasal passages or saliva. Highly specific (low rate of false positives). But potential for false-negatives, particularly for samples collected too soon after a person is exposed. [Note that virus genetic material can sometimes be detected by PCR long after a person is no longer infectious.]

Serology (antibody detection): For people who may have been infected in the past but were unable to obtain a test. Tests for antibodies in blood (i.e., immune responses specific to COVID infection). Variable performance makes serology useful for estimating the proportion of people in a population that have been exposed to COVID, but unreliable as a diagnostic test for individuals.

Antigen (virus detection): For people who think they have an active infection. Detects viral proteins in saliva or tissue swabbed from the nasal cavity. Cheap, fast, but considered unreliable. Only one antigen test so far has a EUA.

False Negative: A test that incorrectly gives a negative result for a person infected with COVID.

False Positive: A test that incorrectly gives a positive result for a person who is not infected with COVID.

Sensitivity: Proportion of test results that are false negatives.

Specificity: Proportion of test results that are false positives.

Positive Predictive Value: Probability that a positive test result correctly reflects that a patient has COVID-19. Depends on the performance specifications of a test (sensitivity and specificity) and how widespread the disease is in a community — a situation that can change rapidly. 

Further reading:

Why some Covid-19 tests in the US take more than a week, MIT Technology Review

Individual EUAs for Molecular Diagnostic Tests for SARS-CoV-2

COVID 19 Testing – Guide for Physicians

Coronavirus antigen tests: quick and cheap, but too often wrong? Science

US test trends, Johns Hopkins University

COVID and Schools: Will It Work?

The social and economic benefits of opening schools are enormous. For kids. For parents. For parents’ employers.

Low COVID infection rates of children combined with other countries reopening schools have made US officials bullish about sending kids back to the classroom this fall.

But the question Should schools open? may not be as important as Will they stay open? Recurring outbreaks in a school district could mean a return to online learning exclusively. The hard truth is that no matter how determined parents, government officials, and administrators are right now to open classrooms this fall, schools will close if there are major outbreaks in schoolchildren and teachers, as has occurred in many countries.

Israel presents a cautionary tale. Two weeks after reopening schools in May, 116 students and 14 teachers were infected at a single middle school/high school, leading to the closing of all schools and a curtain call on the country’s jubilant reopening. It raises the question: What are the prospects of US schools actually staying open this fall?

South Korea responds to a COVID infection in a 6-year old in May, causing schools to close and setting back plans to enter phase 2.

The answer depends a lot on where you live. If you open two schools today with the exact same protocols in Vermont and Florida, the Vermont school will have a much higher likelihood of avoiding outbreaks and still being open two weeks later. It’s simply a numbers game. Vermont had 16 new COVID cases last week. Just 0.8% of VT tests returned positive for COVID. This rate is similar to countries in Europe and Asia that have been able to open schools (Denmark, Norway, Germany, UK), which all have less than 1% of COVID tests positive. In comparison almost one-fifth of tests in Florida are positive for COVID right now. A school in Florida that tries to open up right now will be bombarded with index cases coming in from the community. The more index cases, the higher the chance that one of those kids will turn out to be a superspreader.

COVID levels are much lower in Europe and Asia.

Can’t they keep COVID out of the school with daily screening? The problem is that kids tend to be asympatomic. If you’re not testing kids for live virus and only doing screening based on temperature checks and reported symptoms you’re going to miss a lot of silent cases. The problem is compounded when asymptomic kids transmit to other asymptomatic kids, creating chains of silent transmission that don’t get detected until someone (student or teacher) finally comes down with symptoms. A recent outbreak of COVID at a YMCA summer camp in Georgia, despite all counselors and campers passing all mandatory screenings, shows just how hard it is to keep the virus out of a group of kids.

Won’t face masks and social distancing keeping the virus from transmitting between kids at school? Schools will do everything in their power to keep viral transmission limited within their classrooms, including smaller class sizes, limited mixing, social distancing, and trying get kids to wear masks. For better or for worse, there will be an enormous amount of Lysol. But let’s be realistic: a COVID plan that rests on teachers keeping schoolchildren physically distanced from each other at all times and with their masks is a plan with a lot of holes. Summer camps have already closed after COVID outbreaks in Missouri, Texas, and Arkansas, despite social distancing, masks, and mandatory quarantines before arrival. You think we can keep COVID from transmitting in kids? We can’t even control COVID in military units.

What are we asking of teachers when we can’t even keep COVID out of US troops?

Ventilation in schools is also a vulnerability. Especially as there is growing concern by scientists that airborne transmission by fine aerosols has been underestimated, particularly in settings with close contact and poor ventilation. Notably CDC’s lengthy guidance for schools lacks any recommendations to move activities outdoors, which is logistically challenging but probably the most effective way to reduce transmission among schoolchildren, especially by aerosol.

Teachers also won’t have a potent weapon in the arsenal against COVID: testing. Professional athletes get routine COVID testing because it’s so important to catch index cases immediately before they spread. (Although there have been testing failures even for pro baseball players). US soldiers get tested before they go to bootcamp. Right now routine testing of schoolchildren in any capacity isn’t even on the table. Even in areas hardest hit by COVID.

This is terrifying. Maybe I shouldn’t send my kid to school after all. The overall health risks for children are low compared to the enormous benefits of in-person education. Kids are not at zero risk for severe COVID disease. The multisystem inflammatory syndrome (MIS-C) has appeared in dozens of US children infected with COVID. And if schools open and more kids get infected there are certain to be deaths, particularly among teenagers. It’s just a numbers game. But children (unlike adults) may be more likely to die from influenza and other diseases acquired at school than from COVID. According to CDC data there have been 21 confirmed COVID deaths in children ages 1-14 in the US so far. As comparison, 185 children (<18y) died of seasonal influenza last winter.

COVID is not the only disease that is more severe in adults than children. Measles, mumps, rubella, and chicken pox are also, for various reasons, more severe in adults than in children. Kids and adults may have different distributions of the ACE2 receptor that the SARS-CoV-2 virus attaches to on host cells. We have a long way to go in understanding how young people’s less-developed immune systems respond differently to COVID infections than adults. And this remains a critical area of ongoing research.

So what’s all the fuss about? There’s a lot we still don’t know about how kids fit into the bigger picture for COVID transmission. Will schoolchildren take the virus home and infect higher risk parents and grandparents? Will outbreaks in schools spill over into the community? Are we setting up schoolteachers to be sacrificial lambs, especially as a substantial number of teachers are older or with conditions that put them in COVID risk groups?

Preliminary data suggests that kids are about half as likely as adults to get infected in the first place. And far less likely to get severe disease. But they a lot more contacts. And infected kids do shed virus at high levels and some studies suggest they transmit to other people efficiently, perhaps as well as adults. But scientists bemoan the lack of data needed to answer these big questions.

Sweden was a real missed opportunity to study COVID transmission in children. The country kept schools open all spring but never collected the data needed to study transmission chains. Preliminary findings in Sweden suggest that around 5% of kids 0-19 had antibodies to COVID, compared to 7% of adults 20-64.

New data on kids and COVID could also come out of the US this summer. Over 1700 staff and kids at daycares in Texas have been infected with COVID since the state’s reopening in late spring, representing a 759% increase since June 15. But we still don’t know the direction of transmission and whether the index cases tended to be staff or kids.

But we should be realistic about what we’re asking of teachers. School administrators and teachers will be working all summer to redesign schools for COVID, following detailed CDC and state and local guidance. But there are enormous logistical hurdles. Even just getting kids to the school is a challenge, especially in cities where school kids take public transit.

It’s critical to recognize that the success of in-person schooling does not fall on the teachers, but the entire community. If we want schools to succeed, we can’t just focus on what happens within a school’s wall. Americans understood the need to social distance to flatten the curve to keep hospitals running. Will they rally around a national strategy to get kids to school? Will Americans start connecting the dots? And recognize that individual decisions about going to a party or wearing a mask impact the downstream likelihood of a five-year old being able to attend kindergarten.

Many US school districts can’t realistically get COVID down to European levels (<1%) by August. What happens in school districts with higher COVID levels will be a grand national experiment. But a collective failing to control COVID this summer means that teachers in areas with high COVID levels may not have a fighting chance this fall. Even magical fairy teachers that can somehow get teenagers to faithfully wear masks and keep 8-year olds six feet apart.

We also need to flexible. Parents may object to a hybrid model of in-person and online education, but this may more realistic in schools districts with higher levels of COVID. Demanding that all schools provide only full-time in-person schooling could backfire by increasing the risk that school outbreaks shutter classrooms entirely. The geographical heterogeneity of COVID in the US means that we need to be particularly flexible and tailor educational strategies specifically to local COVID risk levels. Levels of COVID in a community can change dramatically from week to week, and school districts also need the flexibility to adapt quickly to changing conditions, sometimes preemptively and before the need for change is universally recognized by all members of the community.

TL;DR: America’s grand experiment with opening schools in the middle of a COVID pandemic begins in August. Parents can’t wait. Teachers are wetting themselves. But the experiment could fail quickly if we don’t bring COVID levels down far enough in our communities to avoid school outbreaks and closures.