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

TLDR

Autoantibodies that neutralize type I interferons are produced by patients with APS‑1 and have been shown to account for at least 10 % of life‑threatening COVID‑19 pneumonia cases in the general population. The study examined 22 APS‑1 patients from 21 kindreds across seven countries, aged 8–48 years, who were infected with SARS‑CoV‑2 since February 2020. Among these patients, 86 % were hospitalized for COVID‑19 pneumonia, 68 % required ICU admission, 50 % needed mechanical ventilation, and 18 % died, indicating that preexisting neutralizing auto‑antibodies to type I IFNs confer a very high risk of severe disease at any age.

Abstract

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.