Abstract
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-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (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 life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
Highlights
Interindividual clinical variability in the course of SARS-CoV-2 infection is immense
We examined 663 individuals infected with SARS-CoV-2 presenting asymptomatic or mild disease, and 1,227 healthy controls whose samples were collected before the COVID-19 pandemic
We found that plasma from the five patients with neutralizing auto-Abs tested neutralized the protective activity of IFN-α2 in Madin–Darby bovine kidney (MDBK) cells infected with vesicular stomatitis virus
Summary
Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α [36], or both [52], at the onset of critical disease; a few had autoAbs 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. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men. Neutralizing IgG autoAbs against type I IFNs can occur in patients treated with IFN-α2 or IFN-β [15] and exist in almost all patients with autoimmune polyendocrinopathy syndrome type I (APS-1) [16] They are seen in women with systemic lupus erythematosus [17]. Auto-Abs against type I IFNs were detected in two unrelated patients for whom we had plasma samples obtained before SARS-CoV-2 infection, indicating that these antibodies were present before SARS-
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