Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1
Christian Meisel, Bengisu Akbil, Tim Meyer, Erwin Lankes, Victor M. Corman, Olga Staudacher, Nadine Unterwalder, Uwe Kölsch, Christian Drosten, Marcus A. Mall, Tilmann Kallinich, Dirk Schnabel, Christine Goffinet, Horst von Bernuth
Christian Meisel, Bengisu Akbil, Tim Meyer, Erwin Lankes, Victor M. Corman, Olga Staudacher, Nadine Unterwalder, Uwe Kölsch, Christian Drosten, Marcus A. Mall, Tilmann Kallinich, Dirk Schnabel, Christine Goffinet, Horst von Bernuth
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Concise Communication Immunology

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

Abstract

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.

Authors

Christian Meisel, Bengisu Akbil, Tim Meyer, Erwin Lankes, Victor M. Corman, Olga Staudacher, Nadine Unterwalder, Uwe Kölsch, Christian Drosten, Marcus A. Mall, Tilmann Kallinich, Dirk Schnabel, Christine Goffinet, Horst von Bernuth

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Figure 2

Auto-Abs in patients with APS-1 neutralize the ability of type I IFNs to inhibit SARS-CoV-2 infection.

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Auto-Abs in patients with APS-1 neutralize the ability of type I IFNs to...
Calu-3 cells were mock treated (no serum) or pretreated with indicated concentrations of human serum in the presence or absence of 200 IU/mL IFN-α2a (A and D) or 5 ng/mL IFN-ω (B and E) for 16 hours before infection. IFN and serum were removed, and cells were infected with SARS-CoV-2 at an MOI of 0.01 for 1 hour, washed, and fresh medium was applied to the cells. Twenty-four hours after infection, supernatant was harvested for viral RNA extraction and plaque assays. (A–C) Viral RNA was extracted from supernatant and SARS-CoV-2 genome equivalents/μL were quantified by qRT-PCR using primers targeting the E gene region. (D–F) Supernatants were titrated on Vero E6 cells and incubated for plaque formation for 3 days. Plaques were counted and PFU/mL was determined. Data were generated in 2 independent assays. Values obtained in the absence of serum and IFN were set to 100%.