Autoantibodies neutralizing type I interferons linked to severe COVID-19 pneumonia in myasthenia gravis patients

This international cohort study examined 85 unvaccinated SARS-CoV-2-infected myasthenia gravis (MG) patients who received no antiviral treatment. The study assessed the association between the presence of autoantibodies neutralizing type I interferons (AAN-I-IFN) and the risk of developing hypoxemic COVID-19 pneumonia, comparing MG patients with and without these autoantibodies.

Patients with AAN-I-IFN neutralizing both IFN-α2 and IFN-ω had a 12.7-fold increased odds of hypoxemic pneumonia (95% CI 2.1-78.9, p=0.0010). Those with antibodies neutralizing IFN-α2 at any dose had a 4.7-fold increased odds (95% CI 1.5-15.0, p=0.0054). MG patients had a 28.9-fold higher odds of producing AAN-I-IFN compared to the general population (95% CI 10.8-77.7, p=4.9x10^-27). Patients with thymoma had higher prevalence of AAN-I-IFN (64% vs 27%, OR 5.6) and a 9.2-fold increased odds of hypoxemic pneumonia (95% CI 1.9-44.2, p=0.0019). Safety and tolerability data were not reported.

Key limitations include the observational design, which precludes causal conclusions, and the exclusion of vaccinated or antiviral-treated patients, limiting generalizability. The small sample size of 85 patients and lack of reported absolute event numbers warrant caution. The findings suggest an association between AAN-I-IFN and severe COVID-19 outcomes in this specific MG population, but clinical relevance for patient management remains uncertain and requires validation in larger, more diverse cohorts.