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 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 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. 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.
Auto-antibodies against type I IFNs in patients with life-threatening COVID-19 / Bastard, P., Rosen, L.B., Zhang, Q., Michailidis, E., Hoffmann, H., Zhang, Y.u., Dorgham, K., Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., et al.. - In: SCIENCE. - ISSN 0036-8075. - (2020), p. eabd4585. [Epub ahead of print] [10.1126/science.abd4585]
Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
Aiuti, Alessandro;Casari, Giorgio;Piemonti, Lorenzo;Ciceri, Fabio;
2020-01-01
Abstract
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 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 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. 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.| File | Dimensione | Formato | |
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