Examination of autoantibodies to type I interferon in patients suffering from long COVID

Long COVID (LC) is an emerging global health concern. The underlying mechanism and pathophysiology remain unclear. Presence of neutralizing autoantibodies against type 1 interferons (IFN) has been established as a predictor of critical COVID‐19. We hypothesized that persistent autoimmune activity with autoantibodies against type 1 IFN may contribute to symptoms in patients with LC. Plasma samples and clinical information were obtained from a Danish LC cohort consisting of adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Information on symptoms and quality of life was derived from an LC‐specific questionnaire and the EQ‐5D‐5L questionnaire. Detection of type 1 IFN autoantibodies in plasma were performed by ELISA. Samples collected between June, 2020, and September, 2021, from 279 patients were analyzed and compared to a control group of 94 individuals with prior mild SARS‐CoV‐2 infection who did not develop LC symptoms. In total, five LC patients (1.8%) and 3 (3.2%) of the controls had detectable circulating type 1 IFN autoantibodies. Collectively, prevalence of autoantibodies against type 1 IFN subtypes in our LC cohort were primarily driven by men and did not exceed the prevalence in controls. Thus, in our cohort, anti‐type I IFN autoantibodies are unlikely to drive LC symptoms.