The Good (But Not Great) News About T-Cells and Herd Immunity
The Good (But Not Great) News About T-Cells and Herd Immunity
Over the six months of the COVID-19 pandemic, you would never have gone broke betting on the disease continuing to surprise — on its apparent ability to grow weirder, less predictable, and less consistent, at times by the day. What first looked like a simple respiratory disease produced, over time, disorienting, diverse damage — in lungs, in hearts, in brains.
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In theory, 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).
The decline is quite striking, and probably deserves more attention than it has been given to date, as those following the pandemic closely within the media (and without) have fallen into simplistic debates about whether cases and deaths are rising, and whether they will continue to.
As cases exploded in the U.S. earlier in the summer when the country came out of lockdown, some rise in deaths was inevitable. But 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.
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.
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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Mateus J, Grifoni A, Tarke A, et al. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 2020:eabd3871. Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans | Science
Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.
