1/ In this 2nd @SciImmunology paper (immunology.sciencemag.org/content/6/62/e…), we show pre-existing auto-Abs neutralizing low physiological concentrations of type I IFNs account for 15% of critical COVID-19 cases, including 20% of critical cases in patients >80 yrs and 20% of deaths across ages.
2/ We tested 100-fold lower concentrations of type I IFN than in our previous report (science.sciencemag.org/content/370/65…). We also found that, in most patients, these auto-Abs neutralize IFN-alphas and/or -omega, while other patients carry auto-Abs that neutralize IFN-beta only.
3/ The penetrance for critical COVID-19 pneumonia is high, but depends on the nature of the auto-Abs (e.g. neutralization of both IFN-alphas and -omega versus -omega only), as indicated by the varying odds ratios. 
4/ By testing >30,000 uninfected subjects in the general population aged 18 to 100 years, we confirm that these auto-Abs precede SARS-CoV-2 infection, in about 0.5% of people younger than 60 years.
5/ Moreover, the prevalence of auto-Abs to IFN-alphas and -omega sharply increases with age, reaching 4% over age 70 years and up to 7% between 80 and 85 years.
6/ In contrast, the prevalence of auto-Abs neutralizing (high concentrations of) IFN-beta seems to be independent of age, stable in all age categories.
7/ These findings confirm and expand our earlier report that 10% of COVID-19 critical cases are due to pre-existing auto-Abs neutralizing 100-fold higher concentrations of type I IFN (science.sciencemag.org/content/370/65…; rupress.org/jem/article-ab… & rupress.org/jem/article/21…).
8/ Replications of the latter study in cohorts from Lyon, Amsterdam, Madrid, San Francisco, and New Haven have been published (papers below). It now becomes important to test neutralization of lower concentrations of type I IFN, including IFN-beta, in these and other cohorts.
9/ rupress.org/jem/article/21…, link.springer.com/article/10.100…; link.springer.com/article/10.100…; link.springer.com/article/10.100…; biorxiv.org/content/10.110…; nature.com/articles/s4158…
10/ Overall, we show that 4% of people > 70 years carry auto-Abs neutralizing physiological concentrations of type I IFN-alphas and -omega, which contributes to the much greater risk of critical COVID-19 in the elderly population.
11/ This new CHGE (covidhge.com) effort was led by Paul Bastard and @LaurentAbel4, with the extraordinary collaboration by Adrian Gervais, Tom Le Voyer, @_jmanry_, @AarhusUni_int, @adamhdyer, @AlexandreBelot, @anne_puel, @AurelieCobat, @BeziatV, @Boisson_Bebo...
12/ @Castagnoli_R, @CatherineMBiggs, @dan_leung_, @DanyAnglicheau, @DonaldVinh, @felipereye, @Fran_Morandeira, @GorochovG, @IsabelleMeyts, @jacquesfellay, @JavierMPicado, @JouanguyE, @JRosain, @kai_kisand, @LaurentAbel4, @ldnotar, @Marce_MoncadaV, @MelanieMigaud...
13/ @michailidis_lab, @NicolasdeProst1, @NussenzweigL, @panhammarstrom, @PhilippotQ, @PiemontiL, @PLTharaux, @prandocarolina, @PujolLab, @QuintanaMurci, @RiceLaboratory, @ryangrui, @SanRaffaeleMI, @SatoshiOkada3, @ShenYingZhang1, @SPKennelly, @stutangye, @tutu_ZQ, @xsolanich...
14/ and others not yet on Twitter.
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