Thread by @statesdj

We’re thinking all wrong about the variants. The prevailing narrative is that each new variant comes to dominate because it’s more transmissible than previous variants. A better view may be that it’s immune escape driving viral diversity
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If it was just transmissibility, older viruses would continue to spread, even if somewhat more slowly, but that’s not what’s happening. Older variants are declining in absolute case count suggesting that there is competition between variants
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ncbi.nlm.nih.gov/pmc/articles/P…

How can variants compete with each other? Immune escape. A variant that evades the immunity induced by a different variant can continue to spread while spread of the old variant is limited to only hosts who have not been infected or vaccinated
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We know other human coronavirus evolve to evade immunity. E.g. a nice study of HCov 229E shows over a period of years new variants arise that escape immunity induced by older variants.
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journals.plos.org/plospathogens/…

Other viruses also evolve to escape prevailing immunity. E.g. we have studied immune escape in influenza viruses extensively
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ncbi.nlm.nih.gov/pmc/articles/P…

Can immune escape be important if we are still far from “herd immunity”? First a digression. I don’t like the term “herd immunity”, it implies we are homogeneous and passive. Neither is true. I prefer “community immunity”, it betters captures active measures and behavior
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And importantly, human are not a homogeneous population in either our biology or our behavior. R0 is an artificial construct, and it’s as much a property of the population as it is of the virus
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If we assessed R0 in a closely interacting community of highly susceptible individuals, we might get a very high R0. Estimates of R0 on the Diamond Princess cruise ship range as high as 14 ncbi.nlm.nih.gov/pmc/articles/P…
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Conversely, if we estimated R0 among rural outdoorsman who rarely interacted with others and did so almost entirely in well ventilated outdoor settings, R0 would be quite low. It doesn’t make much sense to talk about R0 as a property of the virus alone
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Back to the question of how variants can compete with other through immune escape is we are still far from community immunity? In our heterogeneous population, a few people have a lot of exposure and many contact
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SARS-CoV-2 has a high dispersion in contagion. Most cases infect no one, a few infect many. Think of a restaurant worker or driver in a poorly ventilated bus. They are exposed to many people, and if they become contagious, they can expose many people.
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theatlantic.com/health/archive…

These highly exposed people in high contact settings are driving the pandemic. They are also among the earliest to be infected and are likely the battle ground for competition between the variants
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It is critical that we develop booster vaccines based on newly emerging variants. How long will this take? Modifying an existing recombinant biology vaccines to use a new spike antigen is quick, days to design, a few weeks to verify its basic properties
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We also have well established regulatory pathways to evaluate the safety and efficacy of vaccines for new variants based on our years of experience with influenza
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fda.gov/files/vaccines…

Typically, clinical trials of a few thousand participants are required to assure safety, and efficacy is assessed using biomarkers such as the induction of neutralizing antibody titers. Both can be assessed relatively quickly
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In this context, the rather abrupt “Boosters aren’t needed” announcement from the CDC and FDA in response to Pfizer’s announcement that new variant boosters are being developed seems premature
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reuters.com/business/healt…

Addendum, a reminder on COI: my company does COVID testing, but we are not currently involved with Pfizer or other vaccine makers

Addendum: there’s strong evidence that variants like alpha and delta are more transmissible, but they are also evading immune responses, and escape an important issue we need to address with reformulated vaccines
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The good news from the Bloom study is that immunity induced by 229E escape variants covers earlier variants well. Makes sense, the viruses are competing with each other. A booster shot based on delta will likely cover earlier variants well journals.plos.org/plospathogens/…
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