Autoantibodies against type I IFNs in patients with life-threatening COVID-19.
Level 4 - case-series / case-control
Case-control observational study comparing critical COVID-19 cases to mild/asymptomatic infections and healthy controls.
PubMed 32972996 · doi:10.1126/science.abd4585
What was done
Researchers screened for neutralizing immunoglobulin G (IgG) autoantibodies against type I interferons (IFNs, including IFN-ω, IFN-α subtypes, and others) in 987 patients with life-threatening COVID-19 pneumonia at critical disease onset. They compared these findings against 663 individuals with asymptomatic or mild SARS-CoV-2 infection and 1,227 healthy controls, testing in vitro whether detected autoantibodies neutralized the antiviral activity of type I IFNs.
What was found
Neutralizing IgG autoantibodies against type I IFNs were detected in at least 101 of 987 patients (10.2%) with life-threatening COVID-19 pneumonia: 13 had autoantibodies against IFN-ω, 36 against 13 IFN-α subtypes, and 52 against both, with a few targeting other type I IFNs. These autoantibodies blocked type I IFN-mediated inhibition of SARS-CoV-2 in vitro. In contrast, 0 of 663 asymptomatic or mild cases and 4 of 1,227 healthy individuals (0.33%) had these autoantibodies. Of the 101 autoantibody-positive patients (aged 25 to 87 years), 95 were men. The authors calculated this autoimmune defect accounted for critical COVID-19 in at least 12.5% of men and 2.6% of women in the cohort.
Why it matters
It identifies a specific pre-existing autoimmune mechanism—neutralization of type I interferon immunity—that explains a substantial fraction of life-threatening COVID-19 cases and partly accounts for the strong male bias in severe disease.
Limits
The abstract does not provide longitudinal data on whether these autoantibodies pre-dated infection in all severe cases or were induced during acute illness, though presence in healthy controls suggests pre-existence. Detailed clinical co-morbidities, ethnicity distributions, and outcomes following specific therapeutic interventions were not reported in the abstract.
Cited by
- supports Genetic mutations that abolish interferon secretion were identified exclusively in severe COVID-19 patients and explained a significant proportion of severe cases in a cohort published in Science.
- supports Autoantibodies neutralizing type I interferon were found in approximately 10% of patients with severe COVID-19, and in none of the mild to moderate patients, in a study published in Science.