Intensive Care Medicine | 2021
COVID-19-associated autoimmunity as a feature of acute respiratory failure
Abstract
Dear Editor, Coronavirus disease 2019 (COVID-19) has similarities to systemic autoimmune conditions, including an association with increased incidence of autoantibodies [1–3], including those directed toward cytokines [4]. However, reports to date lack longitudinal assessments and have inadequate controls (i.e., comparison to different severities within COVID-19 or to healthy individuals). Moreover, previous studies reported the emergence of autoantibodies in severe respiratory and infectious disease [2, 5]. We performed an observational cohort study in which we prospectively enrolled adults with suspected COVID19-associated acute respiratory failure on admission to the intensive care unit (ICU). Patients were classified based on SARS-CoV-2 testing by polymerase chain reaction (PCR). The primary clinical outcome was death in ICU within 3 months; secondary outcomes included in-hospital death and disease severity. Anti-nuclear antibodies (ANA), antigen-specific autoantibodies (spAAB), myositis-related autoantibodies and anti-cytokine autoantibodies (aC-AAB) were measured longitudinally. Patients did not receive any COVID-19-specific therapies since recruitment occurred before any were considered standard of care. The 22 COVID+ and 20 COVID− patients had similar baseline characteristics (Supplement): 69% males, median age 60.5 years, mean APACHE II score 25.3. Sixty-four percent had ANA, 38% had sp-AAB, 31% had myositisrelated autoantibodies, and 38% aC-AAB. Cytoplasmic dense and fine speckled ANA immunofluorescence patterns (AC20 and/or AC19) were significantly associated with worse clinical severity scores (Supplement). Although for some aC-AAB there were large absolute differences between the COVID+ and COVID−, overall, there were no statistically significant differences between the two cohorts for any of the autoantibodies (including anti-interferon autoantibodies[4]), their titers, staining patterns or their temporal development (Fisher’s exact test and ANOVA, false discovery rate q = 0.05; Fig. 1 and Supplement). Given the relatively small sample size, Bayesian analysis was performed to obtain credible estimates of the true differences between COVID+ and COVID− patients. This confirmed the results obtained with hypothesis testing (Fig. 1): no differences were found between COVID+ and COVID− for ANA, sp-AAB or aC-AAB. Sensitivity analysis showed that, based on our results, it would be necessary to assume a priori 15–35% higher prevalence of autoantibodies among the COVID+ for them to be credibly different from the COVID− (Fig. 1). Moreover, even if there were reasons for such assumptions, the resulting posterior mean differences would be on the order of only 15–25% higher autoantibodies among the COVID+ (Fig. 1 and Supplement). We offer two biological and two methodological messages: (1) There was a spectrum of reactivity with high prevalence in the extensive panel of autoantibodies in patients with respiratory failure, an underappreciated phenomenon. Some autoantibodies associated with worse severity deserve longer-term study. (2) Patients with COVID-19-induced respiratory failure *Correspondence: [email protected] 2 Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada Full author information is available at the end of the article