What Will Covid Do Next? A Top Pandemic Doctor Has Some Ideas.

(Bloomberg Opinion) -- One of my favorite stories that I stumbled upon while writing “The Premonition” was of the truly odd and inspiring work done inside the George W. Bush White House between late 2005 and the middle of 2007. Working with a mid-level Centers for Disease Control and Prevention employee named Lisa Koonin, two doctors, Richard Hatchett and Carter Mecher, sought to answer a vexing question: What might society do to protect itself from a new pathogen in the period between the start of a pandemic and the creation of a vaccine? Their work wound up having enormous influence, and the doctors have become known for a peculiar sort of pandemic expertise. Hatchett is now based in London, and runs the Coalition for Epidemic Preparedness Innovations, headquartered in Oslo, which, among other things, helped to fund early production of the new mRNA vaccines. As the omicron variant was emerging, he sat down to answer a few questions about the pandemic and where it might lead. This interview has been edited for clarity.

Michael Lewis: There are early signs that omicron will supplant delta and become the dominant virus, until something comes along to supplant omicron. There are also signs that the existing vaccines might not be as effective at protecting people from the new strain. If all this winds up being true, might we need a vaccine tailored to omicron and — if so — do we wind up chucking all the existing vaccine and return to Go, without collecting $200? Might not this happen over and over again — and we produce billions of doses of vaccines that don't get into people before the virus mutates around them? 

Richard Hatchett: We already know that omicron at least partially evades the immune response elicited by several of our vaccines. Might this happen again? My bet is that it will. Look, we’re going to be living with Covid for a long time and our current vaccines are very good, but that doesn’t mean we can’t develop better ones that provide broad protection against a wide range of SARS-CoV-2 variants, and even against other coronaviruses. Developing such vaccines may take years, because there is a lot of basic virology and immunology work we need to do. Fortunately, there are many groups hard at work chipping away at the problem already. We just need to make sure they are and remain well funded. We need to be thinking about where we want to be with respect to this virus not just next month or next quarter but in five or 10 years.

RH: I think they mostly do. There were some countries that got caught out. Japan initially; even Europe was a little bit short of vaccine relative to the U.K. Australia. New Zealand. They have now caught up and have gotten to a limit where they're running into vaccine hesitancy or people that just don't want to be vaccinated as kind of the boundary.

ML: So rich countries don't have a supply problem, they have a demand problem, and lower-middle-income and lower-income countries have a supply problem.

RH: We have had a supply problem, but that has shifted very recently. Lower-middle-income countries were behind the upper-middle-income countries but had greater access to vaccines than low-income countries. The low-income countries were the ones who really fell off the cliff. In the last few months, the number of doses becoming available through Covax has increased. In November, we delivered close to 200 million doses. The first week of December, we delivered 11 million doses in a day. That’s how much supply picked up.

ML: Can you back up just a second and explain what Covax is and how it came about?

RH: Sure. Covax is the mechanism that was set up by CEPI, Gavi, the World Health Organization and Unicef to fund research and development on Covid-19 vaccines, and then to procure, allocate and deliver them. It was set up as a global sharing mechanism, but because the high-income countries have already taken care of themselves, it has now become essentially a mechanism to rebalance supply to low- and middle-income countries.

ML: Is there a precedent for the attempt to vaccinate the entire world so quickly?

RH: This is the first time it's been done at this scale. There are so many things about the pandemic that are unprecedented.

ML: Is this the first time that there is a sense in rich countries that it's in their interest to vaccinate the world because of the threat of mutation?

RH: I think the way you frame that question specifically, the answer is yes. The first time that a global pandemic was recognized as presenting a national security threat to the United States was with HIV. HIV was in Africa. It was destabilizing and designated a national security threat. But that was a different dynamic. It wasn’t spreading as rapidly. This is the first time that a changing, evolving disease has made this kind of a claim on the attention of world leaders.

But Covid made that claim even before mutation became a major issue and it did that obviously because of the scarcity of vaccines and then the economic impact. Even before the mutations began to demonstrate that they could generate new waves of infection — even after vaccination — we recognized that as long as the virus was circulating freely, and transmission rates were high, that there were going to be opportunities for it to mutate in ways that might allow it to evade the countermeasures that we have.

ML: This has as much to do with the nature of the virus as anything, right? With the flu, you wouldn't worry to this extent that it's going to mutate into something that's going to evade a vaccine.

RH: Actually, there are a lot of analogies with flu. You typically have three or four strains of flu circulating globally. Each of them changes over time, though they don’t seem to change quite as rapidly as Covid. With flu, every year, you have cycles of flu epidemics. They don't devastate society but there's a semi-annual review to make sure the vaccines are the right ones.

Every so often, a flu virus either jumps directly from an animal species, or you have a recombination event where two flu viruses interact and create something that looks brand-new to the immune system. Then you have a virus that has pandemic potential. These occur with the periodicity of maybe 10 years on the short side to maybe 40 or 50 years on the long side.

ML: Is the rate at which Covid seems to be evolving greater than the rate at which flu evolves? Is it just because more people are getting it and so it has more chances to replicate?

RH: You've got a virus that’s trying to optimize for this new environment that it's in. And what's interesting is the kinds of pressure that are put on the virus. There are really two important kinds of pressure that would be put on the virus in a population where nobody's been exposed to it and nobody has any immunity. The virus is racing with the other viruses in the neighborhood. And if a virus can develop an adaptation that makes it transmit faster, then it emerges from the pack and drowns out everybody else and becomes a dominant strain. That’s what delta did. Delta mutated in a way that made it super-transmissible, much more so than the virus was at the outset.

The other kind of pressure that a virus can be subject to is the one that emerges once a population begins to build up immunity. If that immunity has been produced largely through vaccination, then the virus is driven to mutate in a way to evade the immunity provided by the vaccine. The thing we don't really know is how much space the virus has to mutate before the mutations start to impose costs of their own — if it could mutate to a point where it just completely escapes the vaccine, or if there's some kind of limit on what it can do.

What's really striking about omicron is that is has 50 mutations. Delta wiped out other variants because it was so much more transmissible than its competitors, even if its competitors were potentially more lethal. This thing — omicron — looks like it's really souped up to evade whatever immune response the human population has developed. It has mutations in areas that we believe will ramp up its transmission, so it can compete with delta. The numbers that we're seeing coming out of South Africa are not reassuring. Remember, this is summer in South Africa. This is when there shouldn't be a lot of transmission, and yet omicron is exploding there.

ML: So we create these vaccines, we administer them unevenly across the global population, and it creates pressures on the virus to change in certain ways. If we were to set out to create conditions in which the virus was most likely to learn how to evade a vaccine before we're all vaccinated, how different would it be from what we've done?

RH: It would look pretty much like what we've done.

ML: We not only create these miracle vaccines, but the way we've distributed them creates the pressure and the opportunity for the virus to learn how to get around the vaccine before the vaccines can wipe out the virus.

RH: Yes, but the thing I want to be careful not to do is draw a causal link between vaccine inequity and the new variant — I mean, the origins of a new virus variant. It's like rolling the dice a bunch of times. It’s random, but you create conditions that create probabilities. And the conditions we've created would be the ones that would stack the deck toward new mutations emerging.

ML: If I make you God at the beginning of this pandemic, how do you distribute the vaccine to minimize the likelihood that some mutation doesn't end-run the vaccine?

RH: Theoretically, the best answer is to prevent the pandemic altogether. Once you're in a pandemic, the deck is stacked against you. The next answer is you want vaccine manufacturing everywhere, and you want to reduce that period of scarcity to the shortest possible period, and you vaccinate the world in two months, not in two years. But even before that, if I'm really God, what I want to do is this: New scary virus pops up and it's picked up by surveillance and it's sequenced and the world goes, “Oh, my God, we’ve got a scary virus,” and we clamp down in the area where the virus has emerged with non-pharmaceutical interventions to reduce transmission and spread while we rapidly develop a vaccine.

ML: And everybody knows it's only going to be 100 days, so they live with it for 100 days to avoid a pandemic.

RH: Yeah. Live with a severe clampdown in the first areas of transmission and then saturate those areas with vaccine as soon as you've got vaccines and prevent a potential pandemic from becoming a true pandemic. That’s the answer. What we were proposing to do originally was to try to share vaccines globally to protect the most vulnerable. You would have had rates of vaccination globally of approximately 20% to 30%. Everybody would have come up to that floor and protected their vulnerable and reduced deaths and reduced the pressure on health-care systems. But that approach to vaccination would still have produced pressures on the virus.

ML: If you're thinking about strategies of distribution, you can have different goals. One strategy is to minimize death. Another strategy is to minimize transmission, in which case you might vaccinate the population most likely to give Covid to people. And that might be healthy 30-year-olds.

RH: The challenge with a transmission-targeted vaccination strategy is that if you've got a virus that is differentially killing different parts of the population. It’s pretty hard — if you've got a scarce supply of vaccines — not to protect the person who's at risk of dying. You’re trapped, as long as things are driven by scarcity. The long-term solution is to create the conditions that let you eliminate scarcity as quickly as possible. Fortunately, with Covid, the period of scarcity of vaccine has basically come to the end. The supply of vaccine has ceased to be the rate limiter.

ML: So we no longer have a supply problem?

RH: Let me put it this way. The rate-limiting factor of getting people vaccinated is the ability of countries to receive and distribute and dispense the vaccine rather than the supply.

ML: You have any clever ideas about how to fix that?

RH: John Bell, who is the Regius Professor of Medicine at Oxford, has an interesting idea. Most of the poorer countries don't have adult vaccination programs. They're not vaccinating adults for shingles or pneumonia or flu. His idea is that this is really an opportunity to introduce adult vaccination programs globally. If you have those capabilities in place in the long term, that helps.

ML: You're a student of pandemics and of the history of vaccination programs. Did it surprise you how resistant to vaccination the American population is?

RH: Yes, it did. Vaccine hesitancy has been a major concern in the public health community for many years. But the pandemic accelerated it in a variety of ways. We were talking about developing vaccines at record speed. For anyone who has any suspicion of pharmaceutical firms, suspicion of government, suspicion of medicine, that creates a very fertile environment for doubt to creep in — even among people who are kind of in the middle, not just the hardcore anti-vaxxers. And the hardcore anti-vaxxers now have instruments in the form of social media for amplification of their message and for sowing doubt. They have used those tools very effectively.

And then you had an overlay of politicization in the U.S. in particular where it got tangled up with political identity issues. That’s remarkable in some ways, because President Trump had every right to stand up and crow about delivering a vaccine in record time for the American public. You could easily imagine that having been the signature success of his presidency if he had embraced it and told everybody to go out and get vaccinated — but, for whatever reason, he didn't do that.

This is a weird virus in terms of differential rates of risk — high risk in the elderly and the almost negligible risk in the young. You've got a lot of people who have the luxury of being anti-vax or being skeptics, or feeling kind of immune, whether they get the vaccine or not. You can imagine a different scenario where you had some lethal bug, like the 1918 virus, that really hammers young people. That might have led to a different dynamic. My sense is when the threat is salient, people are going to go get the magic bullet. Their willingness to skip the magic bullet depends on their assessment, right or wrong, of their own risk.

ML: Knowing what you know now, if I put you in a time capsule and sent you back to the Bush White House, what would you have done differently?

RH: I’m not sure what I would change. The work we did to develop a pandemic plan, and particularly the work we did to rehabilitate non-pharmaceutical interventions, was important. At the time, nobody was thinking how to systematically use non-pharmaceutical interventions. These are tools that can be used intelligently, in a targeted way, to reduce transmission when countermeasures aren’t available. We need to incorporate using them in a highly targeted way into our planning. It can't just be, “Oh, we're going to do a bunch of stuff.” We had to relearn that lesson with Covid, unfortunately. The way lockdowns were applied initially was not targeted. Lockdowns were effective but came with a huge cost. Our use of such interventions has become more targeted and our ability to adapt to changing epidemiologic conditions has improved over the course of the pandemic.

ML: Would you have done anything to the institutional structure of the American government? What should be the mechanism for trying to coordinate society and a response to any kind of new pathogen, whether it's another variant after omicron or another pathogen?

RH: When you have a new pathogen, it requires decisive action and a tolerance for risk that our institutions are not configured to create. What you need are institutions that have a culture that is designed to produce both the autonomy and the understanding of the need to take risks when you face a threat and have very limited information. The problem is that means a lot of false alarms. If you get it right, you prevent a pandemic — but you pay for success with a lot of false alarms.

ML: Can you think of any American government mechanism that has that capacity?

RH: I would point to the Biomedical Advanced Research and Development Authority. Barda is focused exclusively on biodefense. It doesn't have to worry about maintaining its credibility for public-health interventions. It exists to develop countermeasures against biothreats to the United States. This model morphed into [Operation] Warp Speed, and the one part of the U.S. response that really succeeded in my mind was Warp Speed. You had the military and the technical experts and folks from NIH, and all they cared about were these kinds of threats. That shaped their thinking, it shaped their behavior and it shaped their response.

The problem is that if this is the once-in-a-century problem, an organization that's designed to address a bunch of other problems and has other incentives that drive its culture is not going to be well-adapted to this problem.

Except we’re now in a different world. This is definitely not a once-in-a-century problem. Covid-19 is the seventh global infectious-disease crisis of the 21st century: SARS, avian influenza, swine flu, MERS, Ebola and Zika preceded it. It looks like roughly every three years you're going to have a global infectious-disease crisis, and that tempo is probably increasing. Creating dedicated biodefense organizations might have sounded crazy 30 years ago. It's not crazy now.

ML: The nearest analogy I can think of is climate risk, catastrophic climate events.

RH: I think cyber is also a good example, because threats have increased and changed and become diversified over the last 40 years. Forty years ago, you had to take an infected floppy disk and put it into your computer. Now that we live in, and want to live in, a digitally interconnected world, you've got to invest in security arrangements. Nobody would dream of going onto the internet without an antiviral program.

ML: What do you think the likelihood is that Covid peters out and we forget about it and think this is a once-in-a-century thing?

RH: I think it's much more likely that Covid is going to be like flu and we're going to have annual Covid seasons. Periodically we're going to have mutations emerge and these may give rise to new Covid pandemics. I don't know how often that's going to occur, but I think that's a more likely scenario than it petering out and disappearing from the landscape. So we need to develop the tools to coexist with Covid for the long term. 

ML: If a variant emerges that is not severe, that’s like a cold — a version of the escape fire you light to save yourself from a fire — could you think of that as a vaccine?

RH: It's what we do with live attenuated vaccines. We started fighting polio this way. The Sabin vaccine was a live attenuated vaccine, where people who were vaccinated could actually infect other people. In fact, we speculated early in the pandemic about looking for an escape fire. Some were speculating that kids might be protected from the virus because they were exposed to other non-Covid coronaviruses all the time. If that were the case, should we be squirting non-Covid coronaviruses up people's noses because that would be easy to do, give everybody a cold? But we didn't have enough evidence that it would provide any kind of enduring immunity.

ML: We'd be able to give it to each other instead of the health-care system delivering it. If you could create something that was stable, highly transmissible, not lethal that essentially displaced the current strain of Covid, that might be the most efficient way to create immunity.

RH: That's essentially what happened with the 2009 pandemic flu virus. It was a super-mild flu virus. It had a higher reproductive number than the other flu viruses that it displaced and had a comparatively minimal impact. It knocked the other, more severe flu viruses out of play for a couple of seasons. But I'm not aware of us ever adopting that strategy deliberately.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Michael Lewis is a Bloomberg Opinion columnist. His books include “Flash Boys: A Wall Street Revolt,” “Moneyball: The Art of Winning an Unfair Game,” “Liar’s Poker” and “The Fifth Risk.” He also has a podcast called “Against the Rules.”

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