Interindividual clinical variability in the course of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients
with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing
immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-omega (IFN-omega)
(13 patients), against the 13 types of IFN-alpha (36), or against both (52) at the
onset of critical disease; a few also had auto-Abs against the other three type I
IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block
SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with
asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy
individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were
men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts
for lifethreatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
