Circulating antinuclear autoantibodies were detectable up to 12 months after recovery and were associated with cytokine levels, inflammation markers and persistent symptoms.

Up to 10% of COVID-19 survivors experience ongoing fatigue, headache, dyspnoea on exertion, disturbances of taste and smell, myalgia and cognitive dysfunction. If one or more of these symptoms extends more than three months after initial infection, the syndrome is considered long COVID. It appears to be associated with female sex, severity of the acute phase and vaccination status; nonetheless, its pathophysiology remains obscure. To address the hypo­thesis that long COVID is a virus-induced autoimmune process, researchers in Canada evaluated a panel of antinuclear antibodies (ANA) and antibodies against extractable nuclear antigens (ENA) in a cohort of 106 convalescent COVID-19 patients without history of autoimmune or rheumatic disease (an unspecified pro­por­tion of whom may have been vaccinated or previously infected). Measurements were made three, six  and 12 months after recovery from acute COVID-19 of varying severity.

Comparisons between COVID-19 patients and age- and sex-matched non-SARS-CoV-2–infected, unvaccinated controls as well as patients with other respiratory infections showed that ANA levels were higher in COVID-19 patients three months after recovery and decreased thereafter. Patients with greater severity of acute disease also showed relatively higher autoantibody titres. Persistently elevated titres of antibodies against U1-snRNP (a small nuclear ribonucleoprotein) and SS-B/La (an ENA) were significantly associated with fatigue and dyspnoea as well as with proinflammatory cytokines (tumour necrosis factor, interleukin-1), markers of inflammation (C-reactive protein) and D-dimer levels.

Comment: In this small, observational study, a causal relation between the detected autoantibodies and long COVID symptoms cannot be confirmed. Such autoantibodies may have been present all along and subsequently dysregulated by COVID-19 (as any other severe infection could have done). Furthermore, the effect of vaccination prior to infection on auto­antibody formation, symptoms and markers of inflammation was not addressed, but should be a top research priority. Nevertheless, as an editorialist points out, this study takes a critical step forward in elucidating the patho­physiology of this vexing syndrome.

Thomas Glück, MD
Professor of Medicine, University of Regensburg, Chief, Department of Medicine, District Hospital Trostberg, and Chief, Infectious Diseases Consulting Service, Traunstein and Trostberg, Bavaria, Germany.

Son K, et al. Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms. Eur Respir J 2023; 61: 2200970.

Sin DD. Is long COVID an autoimmune disease? Eur Respir J 2023; 61: 2202272.

This summary is taken from the following Journal Watch title: Infectious Diseases