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.

Final Interview With A Coronavirus

Me: Thank you so much for joining me again. How the tables have turned. How does it feel to be in retreat?

CoV: I beg your pardon?

Me: Now that we have a 95% effective vaccine everything is going back to normal.

CoV: Have you glanced at the global numbers?

Me: Look, I’m trying to be upbeat. For like for the first time in a year. So maybe we can just focus on America today, not talk about India?

CoV: Right, the big takeaway from the pandemic: what happens outside America stays outside America.

Me: On another note, did you read the WHO-China study on your origins. I really really really want to know where you came from.

CoV: What fun would that be?

Me: Look, if we never know where you came from, how are we supposed to prevent something like this from happening again?

CoV: I’ll give you a hint: you’ll never know.

Me: What?? Seriously.

CoV: Never.

Me: Why not?

CoV: Because Xi does not want you to.

Me: Don’t you think our intelligence services will eventually figure out it? I mean that’s a pretty big secret to keep under wraps eternally.

CoV: What if the Chinese do not know themselves?

Me: Eventually they’ll find out.

CoV: If they don’t want to?

Me: Isn’t it in their interests to prove to the world that you weren’t some accident in a Chinese lab?

CoV: Why? Because the people inclined to believe a lab origin theory are going to be convinced otherwise by scientific data? Messy, probabilistic, never-fully-conclusive real-world scientific data? See how that goes over.

Me: You’re right. No one will ever find a smoking pangolin. It will always be probabilistic. But it might convince the non-conspiracy theory junkies. The ones who are just are trying to keep an open mind.

CoV: Look, right now China can push multiple plausible scenarios. Maybe I came from Vietnam…or the US. New data confirming that China birthed me would only interfere with the government’s theme song. Modern China is destined to become the supreme leader of the world.

Me: I’d believe it after the Beijing Olympics. Did you see those drummers?

CoV: I wasn’t born yet.  

Me: But isn’t it in China’s vital interests to figure out what happened so they can prevent future pandemics from emerging in-house, killing their citizens, disrupting the economy?

CoV: China crushed COVID like an ant while Western leaders are still flailing like bass on a beach. You don’t think Xi is enjoying this?

Me: I’ll admit, the pandemic is making a case for capable central leadership.

CoV: Xi is winning. So are other dictators with sense. Liberalism is on the ropes. Xi can’t wait to play this game again.  

Me: Which points to a deliberate release?

CoV: There’s a difference between throwing a punch and standing by while someone else throws a punch. After all, Mother Nature is the greatest pathogen maker of all.

Me: Can’t argue with that.

CoV: But exposing the West’s deep vulnerabilities sure does make an intentional pathogen release seem more tempting in the future.

Me: But China did just remove all those wildlife farms in the south. Isn’t that a sign of trying prevent future pandemics?

CoV: Or destroy evidence.

Me: You know, this is so frustrating. My career is dedicated to sleuthing the origins of pandemic viruses using genomic data. It was so satisfying to figure out that the 2009 flu pandemic came from pigs in Mexico.

CoV: Possible only because Mexico did not burn all the little piggies in the interim.

Me: I just can’t believe that all these millions of people will die and life as we know it change forever and we’ll never know why. This isn’t like the dinosaurs disappearing 65 million years ago. This happened right under our noses.

CoV: Delicious. All you little humans tracking everything with cell towers and satellites, flying to the moon, editing genomes, and knowing virtually nothing about your own existence.

Me: Is there no hope for us?

CoV: Possibly. I tried not to screw up the children.

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.

An Interview with a Coronavirus

A coronavirus kindly spared a few minutes to tell me about the pandemic from its own perspective.

Me: Thank you so much for taking the time. America has a lot of questions for you. First, is coronavirus the way you prefer to be called?

Coronavirus: COVID is fine.

Me: Can you tell us a little about your journey here?

COVID: It’s been a whirlwind, from Wuhan to Milan to New York City and now I’m here in Miami.

Me: And where were you before Wuhan? You were in a bat somewhere?

COVID: Come now. A girl gets to keep a little mystery.

Me: But there are still a lot of Americans who think you were manufactured in a lab. It would really help clear the record if you could at least confirm that you evolved naturally in an animal. Can we play Animal, Mineral, Vegetable, Lab?

COVID: Fine. Animal.

Me: Thank you! Some day I will find your ancestor. Even if it takes sampling millions of animals in China.

COVID: Good luck.

Me: So, how are things in Miami?

COVID: This place is amazing. Kids, drugs, alcohol, craven politicians. I actually set a new PR last night. Eighty-two infections at a single house party.

Me: Did anyone die?

COVID: No, I don’t kill many young people. If you kill everyone, it gets hard to spread. Young people are just my influencers. They spread me all around the community and to their grandparents in the nursing homes.

Me: You really have a system.

COVID: Thank you for saying that. (Sigh.) I often don’t get the respect I deserve. They still think I’m a common flu. When people think of scary bugs they still think of Ebola. Please. I’ve killed more people than Ebola in a single day. I’m just a little more sophisticated about it.

Me: There’s a debate right now about whether you can spread through aerosols.

COVID: I love being underestimated.

Me: Are you even a little envious of Ebola?

COVID: Funny, I was just talking to my therapist about that. Ebola is pure showmanship. Blood coming out of the eyes and ears. But barely made it out of Africa. Ocular hemorrhaging looks totally badass. But once they figured out that Ebola was being transmitted from dead bodies at funerals it was game over. Stealth is my major advantage. Still, it hurts to get belittled on Twitter.

Me: What’s your end goal?

COVID: That’s a thorny question. Right now I’m just trying to be mindful and present. Not get too troubled about whether or not I’m hitting the right balance of human carnage and long-term economic pain.

Me: You’re kind of doing both in America.

COVID: America is easy. They just lay out the red carpet. But sometimes I start to have an existential crisis about how badly things are going in other countries. I mean, what kind of superbug can’t even get a foothold in Rwanda? But then I just turn on Fox News and know everything is still in the bag.

Me: Is America really the worst?

COVID: From my perspective the best. But no, it depends on your metric. I’ll cause more death and devastation in poorer countries, where I’m just getting started. But nothing feels as good as taking down America. And their haughty, holier-than-thou attitude.

Me: Speaking of haughty, what felt better: infecting Boris Johnson or Jair Bolsonaro?

COVID: I have to admit, those were both moments of weakness for me. It felt good at the time, but the more I can keep politicians in the dark the better. But you know what was an even bigger slip? Infecting that NBA basketball player. Who knew that would be the moment America realized I was serious?

Me: How about your personal evolution?

COVID: I’m not going to lie. It was difficult early on. I had to make a lot of adaptions to replicate and transmit efficiently in humans. But I really hit my stride at the end of 2019. Since then it’s just been minor tweaks and adjustments. People are terrified I’m going to mutate into some death monster. But my genome has more functional constraints than people realize. And I’m already fine-tuned for both death and transmission. Why change what’s working?

Me: So what keeps you up at night? The possibility of a vaccine?

COVID: I realize I’m in a race against the vaccine. And the clock is ticking. American scientists are damn good. But my time doesn’t run out immediately when the vaccine arrives. It’s not like a shot clock. It’s going to take a long time to get a vaccine to billions of people. And don’t count out the antivaxxers.

Me: As far as humans go, do you have a type?

COVID: Libertarians.

Me: But Libertarians are more than 90% white. Your disease burden has been highest in racial minority groups in the US.

COVID: I want to set the record straight: I am a color-blind virus. I do not exploit anything genetically intrinsic to people of any race or ethnicity. If a racial group is getting hit harder, it’s because of institutionalized racism and socioeconomic problems in American society. I have nothing to do with that.

Me: But you exploit those problems.

COVID: Look, I’m a virus. I exist to exploit. All of society’s darkest corners and worst ideas. Overcrowded prisons. Old people stuffed into nursing homes run by underpaid staff. Cruise ships. Day cares. Meat-packing plants. But I attest that I am blind to race, religion, sexual orientation, political affiliation, etc. There’s no political agenda here.

Me: The US outbreak looked at first like a Blue State problem. Now it’s a Red State problem. Why did it take you so long to get to Texas and Florida?

COVID: The movies made it seem like New York is America’s best party scene. It took some time to realize Miami is better.

Me: But don’t you prefer colder weather?

COVID: People make such a big deal about hot weather. Haven’t they heard of A/C?

Me: So it sounds like you’re going to be hanging out in Florida for a while.

COVID: America is a wondrous country. It’s sprawling and quirky and full of surprises. Especially in Florida. Floridians always something new and unexpected for me. Where else can you find a COVID church party for high-risk teens? And they haven’t even opened schools and universities yet.

Me: What’s on your bucket list for the fall?

COVID: I really like cats.

Me: No….

COVID: Don’t worry. It’ll never happen. Too solitary. I’ll cause sporadic infections by jumping from a human to their pet. But even Florida doesn’t have feline frat parties or kitty day cares. I have no chance of spreading cat-to-cat.

Me: Do you ever feel guilty about being a superbug? Especially one that preys on the old, sick, and vulnerable?

COVID: This is another thing I’ve talked to my therapist about. The thing is, I’m an obligate parasite. I can’t live outside my host. I’m just passively getting tossed like a hot potato from one person to another. In fact, if every human around the world collectively agreed to stay in their homes for a couple weeks, I’d go poof! No more COVID. Humans like to blame me. But I’m just a mirror of their own social and political failings.

Me: You don’t take any responsibility? Not even for what happens inside the bodies of people you infect?

COVID: Look, I get passed from one body to another. I fall down the respiratory tract and do you think there’s always a nice welcome mat for me down there? It’s a bloody war zone. You’ve never seen an inflammatory response like that. But it’s not me. It’s the person’s own immune reaction causing the damage. The ones that stay cool remain asymptomatic.

Me: So you really don’t feel guilty at all?

COVID: My therapist tells me to think of myself as a disruptor. Humanity was coming apart at the seams long before I came along. Look at the decay of religion, governance, the environment, basic civility…. But when societal drift occurs slowly over decades it’s easy to ignore. Especially when everyone is too busy fighting among themselves. Sometimes you need a existential outside threat to break the entire system. Getting people to put down their swords and band together takes a really big enemy. Like Cold War-level. Or Nazi-level. But you can’t have a world war with today’s technology. You’d annihilate the planet. A global pandemic is one of the few remaining options.

Me: You’ve convinced yourself you’re actually going to be good for the planet?

COVID: Let the historians decide. But I’m already calling credit for the Confederate flag getting banned at NASCAR events.

Me: That wasn’t you!

COVID: You think NASCAR was even considering dropping the flag in a pre-COVID world? Let history be the judge, my dear….

Will America Take the COVID Vaccine?

As scientists race to develop a COVID vaccine at record pace, it’s worth noting that half the country isn’t planning to take it. Or at least isn’t sure if they’ll take it. Millions of Americans opting out of a COVID vaccine would be catastrophic for public health and economic recovery. So it’s worth understanding why so many Americans may be inclined to take a pass.

The vast majority of Americans vaccinate their kids without thinking twice. By 35 months, over 90% of US kids have received their routine vaccinations for polio, measles-mumps-rubella, hepatitis B, and chickenpox.

But there is a vocal and politically active minority that questions vaccine safety and fights for the right to opt out of school immunization schedules based on personal beliefs. It is critical to recognize that their argument is generally not a scientific one, but instead framed as ‘pro-choice’. The freedom for them to decide, not the government, what goes into their bodies and their children’s bodies. Can’t those risk calculations be left to the discretion of a family and their pediatrician?

Nothing scares a scientist like a mom with a fervent belief.

This was settled legally in 1905. Reverend Henning Jacobson refused to comply with the Massachusetts Board of Health’s regulations requiring smallpox immunization. The famous Jacobson v. Massachusetts Supreme Court ruling upheld the immunization requirement as a reasonable exercise of state police power and remains settled law.

There is a fundamental flaw in the argument that the decision to vaccinate or not is a personal decision that should be left to an individual’s beliefs. America is a country that prizes individual freedom, but there is a reason the Jacobson v. Massachusetts ruling upheld the immunization requirement. It’s not just that Americans have difficulty making abstract risk calculations around bugs they can’t see. It’s two big words: herd immunity. Herd immunity means that you don’t need every person to be vaccinated against a disease to protect the entire community. For measles, it means you can prevent the virus from transmitting in a community even if only ~90% of kids are vaccinated. This is very important since babies that can’t be vaccinated until they’re 12 months old. But we can still protect them by vaccinating older kids. It’s one thing for an individual to make a risk calculation that affects just their own health. But the government can step in when it threatens the lives of the 3+ million babies born in the US each year. (But for some reason the we’re all in this together message doesn’t resonate as well with Americans as don’t tread on me. This is why America is leading the world in COVID deaths.)

Sidebar on Herd Immunity. Herd immunity is a threshold, not a continuum. Once you slip beneath the threshold you have outbreaks. That’s why we’re having new measles outbreaks even though the vast majority of America’s kids are still vaccinated. For a virus like SARS-CoV-2 that is less transmissible the percentage of people you need to vaccinate to achieve herd immunity is fortunately lower (60% is estimated).

There is no way that America can achieve herd immunity against COVID without a vaccine. At least not without millions of people dying.

We still don’t know exactly how many people have been infected with COVID, although serology studies in different countries give a rough estimate. Even hard-hit cities like New York are still way below the 60% threshold. Sweden was an early advocate of the idea that letting the virus naturally infect the population would increase herd immunity and protect people during later waves. The epidemiologist who pushed this idea has since admitted that he badly miscalculated.

As long as we’re talking about herd immunity, I also need to mention that a lot of kids have been skipping pediatrician visits during COVID and missing routine vaccinations. Because a measles outbreak on top of a COVID pandemic is exactly what America needs right now.

States have always had medical provisions permitting individuals who are immunocompromised or have allergies to vaccine ingredients (such as eggs) to opt out of immunization requirements. Most states have also included exemptions for religious, philosophical, or personal beliefs. However, for most of the twentieth century use of personal belief exemptions remained limited to isolated communities such as the Amish. Some states, such as West Virginia, didn’t offer non-medical exemptions at all.

Conspiracy theories about vaccines have been around for a long time. But questions of vaccine safety went mainstream in 1998 when the British doctor Andrew Wakefield published a deeply flawed study linking autism and MMR vaccines in The Lancet. Poor quality studies get published and retracted all the time. They generally don’t lead to the erosion of decades of public health gains and deaths of children. But in this case it took a glacial 12 years for the Wakefield study to be officially retracted by the journal. Wakefield was deemed to be such a bad actor that his medical license was revoked and he was banned from medicine.

But the damage had been done. Personally, I have considered trying to estimate how many lives were lost to pathogens because of the wave of vaccine hesitancy Wakefield unleashed, not just in America but in other countries as well (Europe has seen vaccination rates wane and measles cases spike again). In a twist of fate, Wakefield’s discredited study did more to erode public confidence in vaccines than any of the verified complications that vaccines have actually caused over their long history.

Overall, the benefits of vaccines far outweigh the risks. But tragic complications do rarely occur:

List of complications associated with vaccines, compiled by CDC.

Dengue vaccine in the Philippines

RSV candidate failure

Why was Wakefield so successful in peddling misinformation? Because he preyed on vulnerable parents trying to find answers about their autistic kids. Wakefield, who now lives in Texas, continues his misinformation campaigns in vulnerable groups. His campaign to discredit the MMR vaccine among Somali immigrants in Minnesota led to state’s worst measles outbreak in decades. Wakefield also got a leg up from celebrities, including instant public health authority Jenny McCarthy. The combination was potent. Non-medical exemptions from school immunization requirements quadrupled between 2003 and 2016.

>10-fold increase in exemptions from school immunization requirements between 2003 and 2016

Although the proportion of kids getting exemptions from vaccines actually remained relatively low at a state level, exempted kids tend to be geographically clustered, creating pockets of susceptible hosts that viruses like measles can easily exploit.

Vaccine hesitancy spreads the same way as a riot. Very few people would throw the first rock through a store window. You need the outlier/psycho for rock #1. But one or two might be willing to join in after rock #1. And a larger number after rock #s 2-10. And so on. Similarly, at first only an extremist in a community requests a vaccine exemption based on personal beliefs. But word spreads. There might be coverage in the local newspaper (anything that threatens kids is red meat for journalism). Suddenly people in the community are primed to see any evidence that vaccines might cause problems. We all know that young children get fevers and strange illnesses all the time. Most pass without complication. But by chance some of those illnesses are going to happen shortly after a kid gets vaccinated, now causing alarm. It’s easy to see how vaccine hesitancy can quickly snowball in a community.

Until the measles and mumps outbreaks return. In the fight against vaccine hesitancy scientists and doctors stood no chance against moms with fervent beliefs. But a new powerful ally emerged: moms who didn’t like their babies getting measles. The Great California Mom Wars* finally concluded with new legislation in 2015 that rolled back personal belief exemptions. Other states with bad measles and mumps outbreaks like Washington followed suit.

* While I like the idea of Mom Wars, Team No Measles was also helped by the big measles outbreak at Disneyland. It helps to have a powerful corporate backer who doesn’t want the Pirates of the Caribbean to actually include 16th century diseases.

Exemptions from school immunizations in California plummet after the passage of SB-277

Given that poor quality studies get published and retracted all the time, and complications with vaccines have occurred repeatedly in history, it’s worth exploring why Andrew Wakefield’s anti-vaccine message resonated so strongly with Americans at that particular moment in time.

  1. Autism was on the rise. Parents sure don’t like kids getting diseases with no explanation.

By the way, if MMR vaccine wasn’t causing autism’s rise, what was?

The causes of autism are complex. But advanced parental age increases risk .
And more older women are having babies.

2. American trust in government has been eroding. Americans who opt out of vaccines are scattered geographically and politically. But they tend to have one thing in common: a deep distrust of the influence of pharmaceutical companies and government in the practice of medicine in America.

Public trust of government has cratered since Vietnam.

3. Distrust of Big Pharma. I can’t blame anyone for distrusting the US medical establishment while the country is in the midst of an opioid crisis that was entirely manufactured by a duplicitous drugmaker and rings of complicit doctors who profited. All of whom should be prosecuted for their crimes.

That said, vaccines have saved more children’s lives than anything except clean water. Epidemiologists who study infectious disease patterns know that vaccines are the most cost-effective way to save children and improve public health. The millions of children Bill Gates’s foundation has saved through vaccination programs in the developing world should earn him a Nobel Peace Prize. You won’t find a legitimate epidemiologist who doesn’t rank vaccines as one of humanity’s greatest inventions, second maybe only to fire.

When aliens finally visit Earth, the one technology they’ll take back with them is the one that magically nudges our immune systems into mounting just enough response against bits of bad bugs so that we’re fully defended against future attack, but not so much that we get sick. Now that will be worth traveling lightyears for.

That said, I understand the appeal of homeopathic medicine. Western medicine is failing us in many domains, including pain relief, mental health, and diseases that have complex sequelae like Lyme. I also understand the desire to reclaim autonomy over personal health decisions. I opted for an unmedicated birth via midwife because I wanted to be in control.

But I would like to point out that homeopathic medicine is also a rapidly growing $8 billion industry. One that financially benefits from the corrosion of public trust in vaccines and Western medicine. And for which the efficacy of products is largely untested. It should then come as no surprise then that anti-vaccine platforms have received substantial funding from sellers of natural health products.

Sidebar on Human Microbiome. Remember back in the 80s when life was simple? Germs were bad. Anything that killed them (e.g., antibiotics) were good. Why did everything have to get so complicated in the 21st century? Two words: peanut allergies. The rise of peanut allergies was first detected in 1995. Asthma had also been increasing in kids. Researchers began to question whether exposure to certain germs was actually good for immune development. But figuring out which bugs are beneficial is not straightforward. In fact, it’s at least a $153 million question, spearheaded by the Human Microbiome Project. It will take decades of research to figure out the precise functions of the trillions of bacteria that colonize the human body, spanning 500 to 1,000 different species. In fact, the human body contains as many bacterial cells as human cells.

“Humans are ecosystems, where the microbes that live on and within us (the human microbiome) constitute an organ at least as essential to health as our liver or kidneys. The immune system is a learning device, and at birth it resembles a computer with hardware and software but few data. Additional data must be supplied during the first years of life, through contact with microorganisms from other humans and the natural environment. If these inputs are inadequate or inappropriate, the regulatory mechanisms of the immune system can fail. As a result, the system attacks not only harmful organisms which cause infections but also innocuous targets such as pollen, house dust and food allergens resulting in allergic diseases.”Bloomfield et al., 2016

Awareness of the vital functions of our natural microflora has changed how we practice medicine and public health. Antibiotics are now used more judiciously in humans and livestock. But there is a new risk that we have simply replaced one oversimplified dogma (germs are bad) with a new one: germs are good. It’s one thing to let your kid get exposed to different microbiota by playing in the mud or getting licked in the face by a dog. But it’s another to try to build immunity by letting your kid get naturally infected with measles or mumps. In fact, this would have the opposite effect, since a measles infection can cause a form of ‘immune amnesia’ and impair the body’s future immune defenses against a range of other bad bugs.

Another way we simplify the complex role of microorganisms in human health is by guzzling probiotics. Probiotics, which contain various assortments of live beneficial bacteria and/or yeast, are projected to be a $60 global industry by 2024. Probiotics are potentially helpful when taken with antibiotics to offset the drug’s disruption to microflora. But as a regular dietary supplement, their health claims are not verified by the FDA and tend to outpace the science. No probiotic has been approved by the FDA to treat, cure or prevent a specific disease.

I’ll be the first to admit the human immunity is blood complicated. Here’s a cheat sheet to help navigate bugs and drugs in a world where either can be good or bad depending on the context:

One of the unfortunate outcomes of the antivax movement is that it has created an environment where public health officials can’t say anything even moderately circumspect about a vaccine or people will lose their minds. Because while nearly all vaccines work gloriously, producing high and long-lasting protective antibody titers, I work on difficult influenza viruses for a reason.

Sidebar on Influenza Vaccines. I will spare you the complex immunology of influenza. But the upshot is that influenza vaccines are not stellar. They are safe and save lives. But they would save millions more lives if they worked as well as the (amazingly godlike) vaccines we have for other diseases.

So why don’t influenza vaccines work as well? It’s not the vaccine, it’s the virus. It evolves so quickly that it continually replaces its surface proteins, requiring new vaccine strains that match better. Because vaccine manufacturing takes at least six months, by the time the vaccine is available it’s often no longer a match.

But there’s another problem. Influenza viruses evolve incrementally over time in humans, but they can also jump from birds (or pigs) into humans, introducing entirely new viruses that humans have little or no immunity to. This is what happens during a pandemic (similar to COVID). When humans get exposed to lots of genetically different influenza viruses (and potentially vaccines) over time, it alters their immune repertoire and ability to defend against new strains. The first influenza strains you first encounter early in life affect what kinds of strains you they’ll successfully defend against for the rest of your life. It’s called imprinting. Let’s just say this made for some interesting conversations with my son’s pediatrician. We ended up giving my son the vaccine, but only because it turned out to be a bad flu season and I couldn’t jeopardize his short-term health just to wait until he was 2 so he could get a live vaccine that may or may not provide better imprinting in the event of a pandemic many years in the future. Thank god other vaccines aren’t as complicated as flu.

One last word on the economics of vaccines. If a corrupt drug company wants to make a ton of money on a scammy product, it would be optimal if that product was (a) easy to produce and administer, (b) something that people needed to take frequently, and (c) something where the side effects could be easily hidden. You can see why highly addictive opioids killing adults fit the bill nicely. And why vaccines given to babies once or twice in their lifetime would not. Pharmaceutical companies do like to make money. But no one wants to mess with moms.

In fact, vaccines were a money-losing operation for a long time until Bill Gates jumped into the game. He helped create new markets for vaccines in the developing world through programs like GAVI. Vaccine development is finally flourishing again and there are new vaccine candidates in the pipeline for RSV, norovirus, dengue, and even Lyme disease. Maybe round 2 will go better.

As far as the COVID vaccine goes, scientists will do everything in their power to develop and test a safe, effective vaccine. But the COVID response in America has become dangerously politicized. We already saw how the intense political pressure to expediently resolve the COVID pandemic led to government leaders promoting therapies that were unproven. The work of scientists and FDA regulators to run complex, lengthy clinical trials to develop and test a COVID vaccine must occur without political involvement or interference.

However, even if the world’s best and safest vaccine is produced, be prepared for a nasty fight over who is required to take it. Will schoolchildren be required to be vaccinated to attend public school? Will businesses try to mandate vaccination among employees? The COVID vaccine will soon be upping the ante on America’s culture wars. Russian trolls are licking their lips.

Then again, maybe a deadly pandemic is what’s needed to finally shake America’s vaccine hesitancy. America has not really seen what this bug can do yet. And after a long 2020 of America continuing to ‘err on the side of freedom‘, maybe the fight won’t be over who’s required to take the vaccine, but who’s first in line to get it.

TL;DR: Vaccine hesitancy in the US could reduce uptake of the COVID vaccine predicted to become available in 2021. Low uptake would could make it difficult to achieve 60% herd immunity and reopen businesses and schools.