Thread by @JeffTownsend

is pleased to communicate an answer to what has often been called one of the greatest unknown factors regarding #COVID19: the durability of immunity upon natural infection.

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A @Nature video listed the durability of immunity upon natural infection as one of four questions regarding COVID-19 (1): “This is a big question, and immunologists are working feverishly to determine what immunity to SARS-CoV-2 could look like.”

.@statnews listed the durability of immunity upon natural infection a most pressing question regarding COVID-19 (2): “People seem to be protected from reinfection,” wrote @DrewQJoseph, @HelenBranswell, and @cooney_liz, “but for how long?”

statnews.com/2020/08/17/wha…

Highly touted (and vitally important) early research on the durability of immunity against reinfection reported that the levels of neutralizing antibodies drop "significantly" in two to three months.

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nature.com/articles/s4156…

nejm.org/doi/full/10.10…

As my colleagues @Yale Akiko Iwasaki @VirusesImmunity and Ruslan Medzhitov correctly noted, these antibody levels were not a durability of immunity: “Dropping antibody counts aren’t a sign that our immune system is failing against the coronavirus”

nytimes.com/2020/07/31/opi…

Apoorva Mandavilli @nytimes reported on some who have speculated that one cannot or only very rarely can get infected again: “Dropping antibody counts aren’t a sign that our immune system is failing against the coronavirus”

nytimes.com/2020/07/22/hea…

nytimes.com/2020/10/13/hea…

Tommy Beer @Forbes reported that “Coronavirus Immunity May Last Years, Possibly Even Decades”
forbes.com/sites/tommybee…

Others have taken a different view and have argued on the basis of a relatively small number of cases that for many infected people immunity to #COVID-19 may already have waned

nypost.com/2020/12/01/nor…

nationalgeographic.co.uk/science-and-te…

Many deemed the question impossible to address because there were too few reinfections. “Only the future can tell us,” immunologist Reinhold Förster is quoted as saying in a @Nature news feature last August.

nature.com/articles/d4158…

To infer the durability of immunity, we applied a phylogenetic approach, ancestral and descendent states analysis, by which we can weight the impact of each known durability inversely by its evolutionary distance and the speed at which the trait evolves.

besjournals.onlinelibrary.wiley.com/doi/full/10.11…

Many have deemed the question impossible to address, because there have been too few reinfections. “Only the future can tell us,” immunologist Reinhold Förster is quoted as saying in a Nature news feature last August.

nature.com/articles/d4158…

Here we report an estimate of the durability of immunity to reinfection by SARS-CoV-2, addressing these conflicting findings and demonstrating that the average natural reinfection time of endemic SARS-CoV-2 is likely to be about one and a half years.

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We show, in a probabilistic context, that within a few months, a non-negligible risk of reinfection by SARS-CoV-2 begins to accrue.

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We have taken advantage of the genetic similarity of SARS-CoV-2 to other closely related coronaviruses. SARS-CoV-2 is unlikely to have evolved a highly divergent interaction with the mammalian immune system compared with its close coronavirus relatives.

nature.com/articles/s4146…

We conducted phylogenetic analyses using the S, M, and ORF1b genes, which were alignable across viral genome sequences of all species, and informative for the reconstruction of a maximum-likelihood molecular phylogeny of human-infecting coronaviruses.

bmcecolevol.biomedcentral.com/articles/10.11…

SARS-CoV-2, SARS-CoV-1, MERS, and the circulating human-infecting coronaviruses HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63 are not so distantly related.

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To infer the durability of immunity, we applied a phylogenetic approach—ancestral and descendent states analysis—by which we can weight the impact of each known durability inversely by its evolutionary distance and the speed at which the trait evolves.

besjournals.onlinelibrary.wiley.com/doi/full/10.11…

An under-appreciated study by @ArthurEdridge et al. collected longitudinal data from archived blood samples on the timings of infections by human-infecting coronaviruses and the antibody levels at which they were infected.

nature.com/articles/s4159…

An under-appreciated study by Edridge et al. collected longitudinal data from archived blood samples on the timings of infections by human-infecting coronaviruses and the antibody levels at which they were infected.

nature.com/articles/s4159…

Modelling antibody decline based on the best available data & applying our phylogenetic analysis to “fill in the gaps” provided peak-normalized antibody levels, daily probabilities of infection, and thus the probability of reinfection through time.

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The phylogeny is informative regarding the durability of immunity in all human-infecting coronaviruses. The estimated immunological resistance to SARS-CoV-2 reinfection is less than that of other seasonal coronaviruses, and most similar to MERS.

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The resulting cumulative probabilities based on our analysis of SARS-CoV-2 give 5% probability of reinfection by 3 months after peak antibody response (~4 months after infection) under endemic conditions w/no interventions, and 50% by ~17 months.

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Our estimate of durability of infection reconciles the seemingly contradictory reports of rare, short-term reinfection with a steady train of immunology results demonstrating a longer-term waning of antibody levels and other immunological parameters.

science.org/doi/10.1126/sc…

Until a long-term cohort study quantifying prior antibody levels and reinfections by SARS-CoV-2 becomes feasible, our analysis of the timeframe for reinfection is the most rigorous science revealing knowledge vital to public health decision-making.

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The durability of immunity against reinfection is crucial to travel restrictions, decisions regarding how students obtain their education, prospective revaccination protocols and all long-term public-health modeling projections for #COVID19.

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Our analysis warns that in the absence of any interventions, reinfections are likely to happen on a 1–2 year timescale.

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The accumulation of herd immunity in the absence of widespread, repeated vaccination will be ineffective at forestalling infection due to #COVID19.

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Individuals who have been previously infected with #COVID19 should get vaccinated, for their own health, and for their love of those they are closest to.

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Many thanks to my collaborators on this recent publication: the tireless @hayley_hassler, Zheng Wang, Sayaka Miura, Jaiveer Singh, Sudhir Kumar, Nancy Ruddle, and @alison_galvani, and my incomparable and enthusiastic coauthor Alex Dornburg.

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