Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia

Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% of unvaccinated patients with life-threatening COVID-19 pneumonia. We report here the presence of auto-Abs neutralizing type I IFNs in the bronchoalveolar lavage (BAL) of 54 of the 415 unvaccinated patients (13%) with life-threatening COVID-19 pneumonia tested. The 54 individuals with neutralizing auto-Abs in the BAL included 45 (11%) with auto-Abs against IFN-alpha 2, 37 (9%) with auto-Abs against IFN-omega, 54 (13%) with auto-Abs against IFN-alpha 2 and/or omega, and five (1%) with auto-Abs against IFN-beta, including three (0.7%) with auto-Abs neutralizing IFN-alpha 2, IFN-omega, and IFN-beta, and two (0.5%) with auto-Abs neutralizing IFN-alpha 2 and IFN-beta. Auto-Abs against IFN-alpha 2 also neutralize the other 12 subtypes of IFN-alpha. Paired plasma samples were available for 95 patients. All seven patients with paired samples who had detectable auto-Abs in BAL also had detectable auto-Abs in plasma, and one patient had auto-Abs detectable only in blood. Auto-Abs neutralizing type I IFNs are, therefore, present in the alveolar space of at least 10% of patients with life-threatening COVID-19 pneumonia. These findings suggest that these auto-Abs impair type I IFN immunity in the lower respiratory tract, thereby contributing to hypoxemic COVID-19 pneumonia.

Automated summary

Autoantibodies neutralizing type I interferons (IFNs) were found in the blood and bronchoalveolar lavage (BAL) of patients with life-threatening COVID-19 pneumonia. The presence of these autoantibodies in the lower respiratory tract suggests impaired type I IFN immunity, contributing to severe COVID-19 pneumonia.