Reasons for COVID-19 Optimism on T-Cells and Herd Immunity - 0 views
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It may well be the case that some amount of community protection kicks in below 60 percent exposure, and possibly quite a bit below that threshold, and that those who exhibit a cross-reactive T-cell immune response, while still susceptible to infection, may also have some meaningful amount of protection against severe disease.
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early returns suggest that while the maximalist interpretation of each hypothesis is not very credible — herd immunity has probably not been reached in many places, and cross-reactive T-cell response almost certainly does not functionally immunize those who have it — more modest interpretations appear quite plausible.
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Friston suggested that the truly susceptible portion of the population was certainly not 100 percent, as most modelers and conventional wisdom had it, but a much smaller share — surely below 50 percent, he said, and likely closer to about 20 percent. The analysis was ongoing, he said, but, “I suspect, once this has been done, it will look like the effective non-susceptible portion of the population will be about 80 percent. I think that’s what’s going to happen.”
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one of the leading modelers, Gabriela Gomes, suggested the entire area of research was being effectively blackballed out of fear it might encourage a relaxation of pandemic vigilance. “This is the very sad reason for the absence of more optimistic projections on the development of this pandemic in the scientific literature,” she wrote on Twitter. “Our analysis suggests that herd-immunity thresholds are being achieved despite strict social-distancing measures.”
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Gomes suggested, herd immunity could happen with as little as one quarter of the population of a community exposed — or perhaps just 20 percent. “We just keep running the models, and it keeps coming back at less than 20 percent,” she told Hamblin. “It’s very striking.” Such findings, if they held up, would be very instructive, as Hamblin writes: “It would mean, for instance, that at 25 percent antibody prevalence, New York City could continue its careful reopening without fear of another major surge in cases.”
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But for those hoping that 25 percent represents a true ceiling for pandemic spread in a given community, well, it almost certainly does not, considering that recent serological surveys have shown that perhaps 93 percent of the population of Iquitos, Peru, has contracted the disease; as have more than half of those living in Indian slums; and as many as 68 percent in particular neighborhoods of New York City
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overshoot of that scale would seem unlikely if the “true” threshold were as low as 20 or 25 percent.
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But, of course, that threshold may not be the same in all places, across all populations, and is surely affected, to some degree, by the social behavior taken to protect against the spread of the disease.
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we probably err when we conceive of group immunity in simplistically binary terms. While herd immunity is a technical term referring to a particular threshold at which point the disease can no longer spread, some amount of community protection against that spread begins almost as soon as the first people are exposed, with each case reducing the number of unexposed and vulnerable potential cases in the community by one
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you would not expect a disease to spread in a purely exponential way until the point of herd immunity, at which time the spread would suddenly stop. Instead, you would expect that growth to slow as more people in the community were exposed to the disease, with most of them emerging relatively quickly with some immune response. Add to that the effects of even modest, commonplace protections — intuitive social distancing, some amount of mask-wearing — and you could expect to get an infection curve that tapers off well shy of 60 percent exposure.
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Looking at the data, we see that transmissions in many severely impacted states began to slow down in July, despite limited interventions. This is especially notable in states like Arizona, Florida, and Texas. While we believe that changes in human behavior and changes in policy (such as mask mandates and closing of bars/nightclubs) certainly contributed to the decrease in transmission, it seems unlikely that these were the primary drivers behind the decrease. We believe that many regions obtained a certain degree of temporary herd immunity after reaching 10-35 percent prevalence under the current conditions. We call this 10-35 percent threshold the effective herd immunity threshold.
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Indeed, that is more or less what was recently found by Youyang Gu, to date the best modeler of pandemic spread in the U.S
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he cautioned again that he did not mean to imply that the natural herd-immunity level was as low as 10 percent, or even 35 percent. Instead, he suggested it was a plateau determined in part by better collective understanding of the disease and what precautions to take
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Gu estimates national prevalence as just below 20 percent (i.e., right in the middle of his range of effective herd immunity), it still counts, I think, as encouraging — even if people in hard-hit communities won’t truly breathe a sigh of relief until vaccines arrive.
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If you can get real protection starting at 35 percent, it means that even a mediocre vaccine, administered much more haphazardly to a population with some meaningful share of vaccination skeptics, could still achieve community protection pretty quickly. And that is really significant — making both the total lack of national coordination on rollout and the likely “vaccine wars” much less consequential.
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At least 20 percent of the public, and perhaps 50 percent, had some preexisting, cross-protective T-cell response to SARS-CoV-2, according to one much-discussed recent paper. An earlier paper had put the figure at between 40 and 60 percent. And a third had found an even higher prevalence: 81 percent.
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The T-cell story is similarly encouraging in its big-picture implications without being necessarily paradigm-changing
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These numbers suggest their own heterogeneity — that different populations, with different demographics, would likely exhibit different levels of cross-reactive T-cell immune response
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The most optimistic interpretation of the data was given to me by Francois Balloux, a somewhat contrarian disease geneticist and the director of the University College of London’s Genetics Institute
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According to him, a cross-reactive T-cell response wouldn’t prevent infection, but would probably mean a faster immune response, a shorter period of infection, and a “massively” reduced risk of severe illness — meaning, he guessed, that somewhere between a third and three-quarters of the population carried into the epidemic significant protection against its scariest outcomes
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the distribution of this T-cell response could explain at least some, and perhaps quite a lot, of COVID-19’s age skew when it comes to disease severity and mortality, since the young are the most exposed to other coronaviruses, and the protection tapers as you get older and spend less time in environments, like schools, where these viruses spread so promiscuously.
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Balloux told me he believed it was also possible that the heterogeneous distribution of T-cell protection also explains some amount of the apparent decline in disease severity over time within countries on different pandemic timelines — a phenomenon that is more conventionally attributed to infection spreading more among the young, better treatment, and more effective protection of the most vulnerable (especially the old).
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Going back to Youyang Gu’s analysis, what he calls the “implied infection fatality rate” — essentially an estimated ratio based on his modeling of untested cases — has fallen for the country as a whole from about one percent in March to about 0.8 percent in mid-April, 0.6 percent in May, and down to about 0.25 percent today.
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even as we have seemed to reach a second peak of coronavirus deaths, the rate of death from COVID-19 infection has continued to decline — total deaths have gone up, but much less than the number of cases
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In other words, at the population level, the lethality of the disease in America has fallen by about three-quarters since its peak. This is, despite everything that is genuinely horrible about the pandemic and the American response to it, rather fantastic.
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there may be some possible “mortality displacement,” whereby the most severe cases show up first, in the most susceptible people, leaving behind a relatively protected population whose experience overall would be more mild, and that T-cell response may play a significant role in determining that susceptibility.
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That, again, is Balloux’s interpretation — the most expansive assessment of the T-cell data offered to me
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The most conservative assessment came from Sarah Fortune, the chair of Harvard’s Department of Immunology
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Fortune cautioned not to assume that cross-protection was playing a significant role in determining severity of illness in a given patient. Those with such a T-cell response, she told me, would likely see a faster onset of robust response, yes, but that may or may not yield a shorter period of infection and viral shedding
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Most of the scientists, doctors, epidemiologists, and immunologists I spoke to fell between those two poles, suggesting the T-cell cross-immunity findings were significant without necessarily being determinative — that they may help explain some of the shape of pandemic spread through particular populations, but only some of the dynamics of that spread.
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he told me he believed, in the absence of that data, that T-cell cross-immunity from exposure to previous coronaviruses “might explain different disease severity in different people,” and “could certainly be part of the explanation for the age skew, especially for why the very young fare so well.”
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the headline finding was quite clear and explicitly stated: that preexisting T-cell response came primarily via the variety of T-cells called CD4 T-cells, and that this dynamic was consistent with the hypothesis that the mechanism was inherited from previous exposure to a few different “common cold” coronaviruses
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“This potential preexisting cross-reactive T-cell immunity to SARS-CoV-2 has broad implications,” the authors wrote, “as it could explain aspects of differential COVID-19 clinical outcomes, influence epidemiological models of herd immunity, or affect the performance of COVID-19 candidate vaccines.”