DOI: 10.1073/pnas.2518581123 ISSN: 0027-8424

High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies

Adrian Gervais, Astrid Marchal, Alexis Maillard, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Lucy Bizien, Jessica Peel, Axel Cederholm, Mélanie Migaud, Sylvie Pons, Kahina Saker, Pascal Laforet, Mélodie Aubart, Cyril Gitiaux, Catherine M. Biggs, Rafael Leon Lopez, Sarah Souvannanorath, Céline Tard, Aleksandra Nadaj Pakleza, Aude-Marie Grapperon, Nicholas Heming, Djillali Annane, Annie Verschueren, Shahram Attarian, Kévin Bigaut, Karolina Hankiewicz, Ludivine Kouton, Rocio-Nur Villar-Quiles, Cécile Cauquil, Marie-Céline Fleury, Emilie Rocher, Guillaume Nicolas, Eduardo de Paula Estephan, Maria da Penha Ananias Morita, Edmar Zanoteli, Zakaria Saied, Amine Rachdi, Amouri Rim, Samir Belal, Samia Ben Sassi, Annemarie Hübers, Emmanuel Faure, Isabelle Desguerre, Clémence Basse, Nicolas Girard, Vivien Béziat, Qiang Pan-Hammarström, Lennart Hammarström, Aaron Bodansky, Audrey V. Parent, Mark S. Anderson, Joseph L. DeRisi, Sophie Demeret, Frédérique Truffault, Romain Fort, Florence Ader, Florent Wallet, Sophie Trouillet-Assant, Laurent Abel, Thierry Molina, Marie-Alexandra Alyanakian, Rozen Le Panse, Guilhem Solé, Aurélie Cobat, Nils Landegren, Jean-Laurent Casanova, Anne Puel, Paul Bastard, Emmanuelle Jouanguy
Show PDF Cite

Patients with myasthenia gravis (MG) may produce autoantibodies neutralizing type I interferons (AAN-I-IFN), which underlie severe viral diseases, including critical COVID-19 pneumonia, in patients without MG. We studied an international cohort of 85 unvaccinated SARS-CoV-2-infected MG patients not given antiviral treatment. Hypoxemic pneumonia occurred in 48 of these patients, including 22 (45.8%) with AAN-I-IFN, which neutralized both IFN-α2 and IFN-ω in 14 (29.2%) patients. Six (16.2%) of the remaining 37 patients had AAN-I-IFN, neutralizing both IFN-α2 and IFN-ω in three patients. The risk of hypoxemic pneumonia was greater in MG patients with AAN-I-IFN neutralizing 10 ng/mL of both IFN-α2 and IFN-ω (odds ratio and 95% confidence interval (OR [95% CI]): 12.7 [2.1 to 78.9], P = 0.0010) or IFN-α2 at any dose (OR [95% CI]: 4.7 [1.5 to 15.0], P = 0.0054) than in those without such autoantibodies. The risk of producing AAN-I-IFN was much higher in MG patients than in the general population (OR [95% CI]: 28.9 [10.8 to 77.7], P = 4.9 × 10 −27 ). Thymoma was found in 14 patients and increased the risk of AAN-I-IFN (64% versus 27%, (OR [95% CI]: 5.6 [1.6 to 19.4], P = 0.0050) and hypoxemic pneumonia (9.2 [1.9 to 44.2]; P = 0.0019). Thymoma is, thus, associated with a higher risk of producing AAN-I-IFN, which are, in turn, associated with a higher risk of developing life-threatening COVID-19 pneumonia in patients with MG.

More from our Archive