Observational study: prospective longitudinal cohort (Green)
Inter-individual clinical variability in the course of SARS-CoV-2 infection is immense. In this paper recently published in Science, the authors report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralising IgG auto-antibodies against either interferon (IFN)-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-antibodies against the other three type I IFNs. The auto-antibodies neutralise the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-antibodies were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-antibodies were aged 25 to 87 years and 95 were men. The authors concluded that 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.