Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.

TitlePreexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
Publication TypeJournal Article
Year of Publication2021
AuthorsBastard, P, Orlova, E, Sozaeva, L, Lévy, R, James, A, Schmitt, MM, Ochoa, S, Kareva, M, Rodina, Y, Gervais, A, Le Voyer, T, Rosain, J, Philippot, Q, Neehus, A-L, Shaw, E, Migaud, M, Bizien, L, Ekwall, O, Berg, S, Beccuti, G, Ghizzoni, L, Thiriez, G, Pavot, A, Goujard, C, Frémond, M-L, Carter, E, Rothenbuhler, A, Linglart, A, Mignot, B, Comte, A, Cheikh, N, Hermine, O, Breivik, L, Husebye, ES, Humbert, S, Rohrlich, P, Coaquette, A, Vuoto, F, Faure, K, Mahlaoui, N, Kotnik, P, Battelino, T, Podkrajšek, KTrebušak, Kisand, K, Ferré, EMN, DiMaggio, T, Rosen, LB, Burbelo, PD, McIntyre, M, Kann, NY, Shcherbina, A, Pavlova, M, Kolodkina, A, Holland, SM, Zhang, S-Y, Crow, YJ, Notarangelo, LD, Su, HC, Abel, L, Anderson, MS, Jouanguy, E, Neven, B, Puel, A, Casanova, J-L, Lionakis, MS
JournalJ Exp Med
Date Published2021 07 05
KeywordsAdolescent, Adult, Autoantibodies, Child, COVID-19, Female, Humans, Interferon Type I, Male, Middle Aged, Pneumonia, Polyendocrinopathies, Autoimmune, SARS-CoV-2, Young Adult

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

Alternate JournalJ Exp Med
PubMed ID33890986
PubMed Central IDPMC8077172
Grant ListUM1 HG006504 / HG / NHGRI NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
S10 OD018521 / OD / NIH HHS / United States
R01 AI088364 / AI / NIAID NIH HHS / United States
U24 HG008956 / HG / NHGRI NIH HHS / United States