Mild COVID-19 despite autoantibodies to type I IFNs in Autoimmune-Polyendocrine-Syndrome Type 1 (APS-1).

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

Autoantibodies to interferon(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 six patients with APS-1 between April 1st, 2020 and April 1st, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies to IFN-αand IFN-ω. The patients ́ sera ability 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 four patients with APS-1 and pre-existing high titers of neutralizing autoantibodies to IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnoea, oxygen requirement or high temperature. All infected patients with APS-1 shared female sex and age younger than 26 years. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.