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Proc Natl Acad Sci U S A
. 2026 Aug 4;123(31):e2518581123.
doi: 10.1073/pnas.2518581123. Epub 2026 Jul 31.
High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies
Adrian Gervais 1 2 , Astrid Marchal 1 2 , Alexis Maillard 1 2 , Tom Le Voyer 1 2 , Jérémie Rosain 1 2 3 , Quentin Philippot 1 2 , Lucy Bizien 1 2 , Jessica Peel 4 , Axel Cederholm 5 , Mélanie Migaud 1 2 , Sylvie Pons 6 , Kahina Saker 6 7 , Pascal Laforet 8 9 , Mélodie Aubart 1 2 10 , Cyril Gitiaux 10 , Catherine M Biggs 11 , Rafael Leon Lopez 12 , Sarah Souvannanorath 13 , Céline Tard 14 , Aleksandra Nadaj Pakleza 15 , Aude-Marie Grapperon 16 , Nicholas Heming 17 18 19 20 , Djillali Annane 17 18 19 20 , Annie Verschueren 16 , Shahram Attarian 16 , Kévin Bigaut 15 , Karolina Hankiewicz 21 , Ludivine Kouton 16 , Rocio-Nur Villar-Quiles 22 , Cécile Cauquil 23 , Marie-Céline Fleury 15 , Emilie Rocher 15 , Guillaume Nicolas 8 9 , Eduardo de Paula Estephan 24 25 , Maria da Penha Ananias Morita 25 , Edmar Zanoteli 24 , Zakaria Saied 26 27 , Amine Rachdi 26 , Amouri Rim 27 , Samir Belal 26 , Samia Ben Sassi 27 , Annemarie Hübers 28 , Emmanuel Faure 29 30 , Isabelle Desguerre 10 , Clémence Basse 30 31 , Nicolas Girard 30 31 , Vivien Béziat 1 2 4 , Qiang Pan-Hammarström 32 , Lennart Hammarström 32 , Aaron Bodansky 33 , Audrey V Parent 34 , Mark S Anderson 34 , Joseph L DeRisi 35 36 37 , Sophie Demeret 38 , Frédérique Truffault 38 , Romain Fort 39 , Florence Ader 7 40 , Florent Wallet 41 , Sophie Trouillet-Assant 6 7 , Laurent Abel 1 2 4 , Thierry Molina 2 42 , Marie-Alexandra Alyanakian # 43 , Rozen Le Panse # 38 , Guilhem Solé # 44 45 , Aurélie Cobat # 1 2 4 , Nils Landegren # 5 , Jean-Laurent Casanova # 1 2 4 46 47 , Anne Puel # 1 2 4 , Paul Bastard # 1 2 4 47 , Emmanuelle Jouanguy # 1 2 4
Affiliations
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.
Keywords: COVID-19; autoantibodies; interferons; myasthenia gravis.
. 2026 Aug 4;123(31):e2518581123.
doi: 10.1073/pnas.2518581123. Epub 2026 Jul 31.
High risk of hypoxemic COVID-19 pneumonia in myasthenia gravis patients with type I IFN autoantibodies
Adrian Gervais 1 2 , Astrid Marchal 1 2 , Alexis Maillard 1 2 , Tom Le Voyer 1 2 , Jérémie Rosain 1 2 3 , Quentin Philippot 1 2 , Lucy Bizien 1 2 , Jessica Peel 4 , Axel Cederholm 5 , Mélanie Migaud 1 2 , Sylvie Pons 6 , Kahina Saker 6 7 , Pascal Laforet 8 9 , Mélodie Aubart 1 2 10 , Cyril Gitiaux 10 , Catherine M Biggs 11 , Rafael Leon Lopez 12 , Sarah Souvannanorath 13 , Céline Tard 14 , Aleksandra Nadaj Pakleza 15 , Aude-Marie Grapperon 16 , Nicholas Heming 17 18 19 20 , Djillali Annane 17 18 19 20 , Annie Verschueren 16 , Shahram Attarian 16 , Kévin Bigaut 15 , Karolina Hankiewicz 21 , Ludivine Kouton 16 , Rocio-Nur Villar-Quiles 22 , Cécile Cauquil 23 , Marie-Céline Fleury 15 , Emilie Rocher 15 , Guillaume Nicolas 8 9 , Eduardo de Paula Estephan 24 25 , Maria da Penha Ananias Morita 25 , Edmar Zanoteli 24 , Zakaria Saied 26 27 , Amine Rachdi 26 , Amouri Rim 27 , Samir Belal 26 , Samia Ben Sassi 27 , Annemarie Hübers 28 , Emmanuel Faure 29 30 , Isabelle Desguerre 10 , Clémence Basse 30 31 , Nicolas Girard 30 31 , Vivien Béziat 1 2 4 , Qiang Pan-Hammarström 32 , Lennart Hammarström 32 , Aaron Bodansky 33 , Audrey V Parent 34 , Mark S Anderson 34 , Joseph L DeRisi 35 36 37 , Sophie Demeret 38 , Frédérique Truffault 38 , Romain Fort 39 , Florence Ader 7 40 , Florent Wallet 41 , Sophie Trouillet-Assant 6 7 , Laurent Abel 1 2 4 , Thierry Molina 2 42 , Marie-Alexandra Alyanakian # 43 , Rozen Le Panse # 38 , Guilhem Solé # 44 45 , Aurélie Cobat # 1 2 4 , Nils Landegren # 5 , Jean-Laurent Casanova # 1 2 4 46 47 , Anne Puel # 1 2 4 , Paul Bastard # 1 2 4 47 , Emmanuelle Jouanguy # 1 2 4
Affiliations
- PMID: 42536442
- DOI: 10.1073/pnas.2518581123
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.
Keywords: COVID-19; autoantibodies; interferons; myasthenia gravis.