Subject: Basic medicine
Subject: Biological sciences
Subject: Health biotechnology
Subject: Health sciences
Year: 2022
Type: Article
Type: PeerReviewed
Title: The risk of COVID-19 death is much greater and age dependentwith type I IFN autoantibodies
Author: Cvetkovski, Aleksandar
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 esti mated 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 predic tor of COVID-19 death.
Publisher:
Relation: https://eprints.ugd.edu.mk/32262/
Identifier: oai:eprints.ugd.edu.mk:32262
Identifier: https://eprints.ugd.edu.mk/32262/1/manry-et-al-2022-the-risk-of-covid-19-death-is-much-greater-and-age-dependent-with-type-i-ifn-autoantibodies.pdfIdentifier: Cvetkovski, Aleksandar (2022) The risk of COVID-19 death is much greater and age dependentwith type I IFN autoantibodies. PNAS, 119 (21).
