@article{Covid_Clinicians-2022_216690,
title = {The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies},
author = {Covid Clinicians and COVID-Storm Clinicians and NIAID-USUHS Immune Response to COVID Group and NH-COVAIR Study Group and Danish CHGE and Danish Blood Donor Study and St. James’s Hospital SARS CoV2 Interest Group and French COVID Cohort Study Group and Imagine Covid Group and The Milieu Intérieur Consortium and COV-Contact-Cohort and Amsterdam UMC Covid-19 Biobank Investigators and Covid Human Genetic Effort and CP-COVID-19 Group and CONSTANCES Cohort and 3C-Dijon Study and Cerba Health-Care and Etablissement Français du Sang Study Group and Manry, J. and Bastard, P.},
month = {may},
year = {2022},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged &lt;70 y and in &gt;4% of those &gt;70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals &lt;70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals &lt;40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.},
volume = {119},
issue = {21},
journal = {Proceedings of the National Academy of Sciences},
publisher = {National Academy of Sciences},
url = {https://doi.org/10.1073/pnas.2200413119},
}
