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.

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?

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.

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”).

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

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.

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.

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).

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.

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.

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.

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.

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.

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.

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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.

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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?

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.

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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.

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.

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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

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.

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.

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?

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.

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.

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.