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