- Published
- 16 May 2022
- Journal article
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
- Authors
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- Source
- Proceedings of the National Academy of Sciences
Full text
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 <70 y and in >4% of those >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 <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 <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.
Cite as
Covid Clinicians, COVID-Storm Clinicians, NIAID-USUHS Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James’s Hospital SARS CoV2 Interest Group, French COVID Cohort Study Group, Imagine Covid Group, The Milieu Intérieur Consortium, COV-Contact-Cohort, Amsterdam UMC Covid-19 Biobank Investigators, Covid Human Genetic Effort, CP-COVID-19 Group, CONSTANCES Cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement Français du Sang Study Group, Manry, J. & Bastard, P. 2022, 'The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies', Proceedings of the National Academy of Sciences, 119(21), article no: e2200413119. https://doi.org/10.1073/pnas.2200413119