Autoantibodies Neutralizing Type I IFNs in the Bronchoalveolar Lavage of at Least 10% of Patients During Life-Threatening COVID-19 Pneumonia
Quentin Philippot, Arnaud Fekkar, Adrian Gervais, Tom Le Voyer, L.S. Boers, Clément Conil, Lucy Bizien, Justin de Brabander, JanWillem Duitman, Alessia Romano, Jérémie Rosain, Marion Blaize, Mélanie Migaud, Maxime Jeljeli, Boualem Hammadi, Aurore Desmons, Astrid Marchal, Esther J. Nossent, Anno Saris, Heder De Vries, Lilian J. Meijboom, Siebe G. Blok, Alex R. Schuurman, Tom D. Y. Reijnders, F. Hugenholtz, Juan J. Garcia Vallejo, Hetty Bontkes, Alexander P. J. Vlaar, Joost Wiersinga, René Lutter, Tom van der Poll, Harm Jan Bogaard, Robert F. J. Kullberg, Shiqi Zhang, Esther J. Nossent, Leo M. A. Heunks, Pieter Roel Tuinman, Peter I. Bonta, Laurent Abel, Saleh Al-Muhsen, Andrés A. Arias, Dusan Bogunovic, Alexandre Bolze, Ahmed A. Bousfiha, Davood Mansouri, Isabelle Meyts, Rebeca Perez de Diego, Vanessa Sancho-Shimizu, András N. Spaan, Stuart G. Tangye, Shen-Ying Zhang, Helen C. Su, Julien Mayaux, Qian Zhang, Emmanuelle Jouanguy, Raphael Borie, Bruno Crestani, Charles Edouard Luyt, Homa Adle-Biassette, Damien Sene, Bruno Megarbane, Aurélie Cobat, Paul Bastard, Lieuwe D. J. Bos, Jean-Laurent Casanova, Anne Puel
Abstract
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-α2, 37 (9%) with auto-Abs against IFN-ω, 54 (13%) with auto-Abs against IFN-α2 and/or ω, and five (1%) with auto-Abs against IFN-β, including three (0.7%) with auto-Abs neutralizing IFN-α2, IFN-ω, and IFN-β, and two (0.5%) with auto-Abs neutralizing IFN-α2 and IFN-β. Auto-Abs against IFN-α2 also neutralize the other 12 subtypes of IFN-α. 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.