TY - JOUR
AU - Covid Clinicians
AU - COVID-Storm Clinicians
AU - NIAID-USUHS Immune Response to COVID Group
AU - NH-COVAIR Study Group
AU - Danish CHGE
AU - Danish Blood Donor Study
AU - St. James’s Hospital SARS CoV2 Interest Group
AU - French COVID Cohort Study Group
AU - Imagine Covid Group
AU - The Milieu Intérieur Consortium
AU - COV-Contact-Cohort
AU - Amsterdam UMC Covid-19 Biobank Investigators
AU - Covid Human Genetic Effort
AU - CP-COVID-19 Group
AU - CONSTANCES Cohort
AU - 3C-Dijon Study
AU - Cerba Health-Care
AU - Etablissement Français du Sang Study Group
AU - Manry, Jérémy
AU - Bastard, Paul
PY - 2022
DA - May
TI - The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
JO - Proceedings of the National Academy of Sciences
VL - 119
IS - 21
DO - https://doi.org/10.1073/pnas.2200413119
AB - 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.
PB - National Academy of Sciences
UR - https://www.research.ed.ac.uk/en/publications/the-risk-of-covid-19-death-is-much-greater-and-age-dependent-with/
KW - Coronavirus (COVID-19)
ER