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

Abstract

Abstract Patients with myasthenia gravis (MG) may produce autoantibodies neutralizing type I interferons (AAN-I-IFN), which have been shown to 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 with no 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, which neutralized 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 [2.1-78.9], p =0. 0010) or IFN-α2 at any dose (4.7 [1.5-15.0], p =0.0054) than in those without such autoantibodies. The risk of AAN-I-IFN production was much higher in MG patients than in the general population (28.9 [10.8-77.7], p =4.9×10 -27 ). Fourteen patients had thymoma, which increased the risk of AAN-I-IFN (64% versus 27%, (OR [95% CI]: 5.6 [1.6-19.4], p =0.0050) and hypoxemic pneumonia (9.2 [1.9-44.2]; p =0.0019). Thymoma is, thus, associated with a higher risk of producing AAN-I-IFN, and these autoantibodies are associated with a higher risk of developing life-threatening COVID-19 pneumonia in patients with MG. Significance Statement Patients with myasthenia gravis (MG) have a higher risk of developing life-threatening COVID-19 pneumonia. In an international cohort of unvaccinated, untreated SARS-CoV-2-infected MG patients, we found that autoantibodies neutralizing type I interferons (AAN-I-IFN) were strongly associated with severe hypoxemic pneumonia. Thymoma further increased the risk of both AAN-I-IFN production and severe disease. These findings suggest a crucial immunological mechanism that could guide risk stratification and targeted interventions for MG patients during viral infections, such as COVID-19.