Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1

• Published in: The Journal of clinical investigation 2021-07, Vol.131 (14)
• Main Authors: Meisel, Christian, Akbil, Bengisu, Meyer, Tim, Lankes, Erwin, Corman, Victor M, Staudacher, Olga, Unterwalder, Nadine, Kölsch, Uwe, Drosten, Christian, Mall, Marcus A, Kallinich, Tilmann, Schnabel, Dirk, Goffinet, Christine, von Bernuth, Horst
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; AIRE Protein; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Autoimmune diseases; Concise Communication; COVID-19 - complications; COVID-19 - immunology; Development and progression; Endocrine gland diseases; Female; Genetic aspects; Health aspects; Humans; In Vitro Techniques; Interferon; Interferon Type I - antagonists & inhibitors; Interferon Type I - immunology; Interferon-alpha - antagonists & inhibitors; Interferon-alpha - immunology; Male; Polyendocrinopathies, Autoimmune - complications; Polyendocrinopathies, Autoimmune - genetics; Polyendocrinopathies, Autoimmune - immunology; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Severity of Illness Index; Transcription Factors - genetics; Virus Replication - immunology; Young Adult
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI150867

Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.