The risk of COVID-19 death is much greater and age dependentwith type I IFN autoantibodies

Cvetkovski, Aleksandar (2022) The risk of COVID-19 death is much greater and age dependentwith type I IFN autoantibodies. PNAS, 119 (21).

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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.

Item Type:	Article
Impact Factor Value:	12.7
Subjects:	Medical and Health Sciences > Basic medicine Natural sciences > Biological sciences Medical and Health Sciences > Health biotechnology Medical and Health Sciences > Health sciences
Divisions:	Faculty of Medical Science
Depositing User:	Aleksandar Cvetkovski
Date Deposited:	28 Sep 2023 09:02
Last Modified:	28 Sep 2023 09:02
URI:	https://eprints.ugd.edu.mk/id/eprint/32262

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