SARS-CoV-2 infection induces the production of autoantibodies in severe COVID-19 patients in an age-dependent manner

Abstract

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) outcomes due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, diabetes, chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health & disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 outcomes (with 71 mild, 61 moderate, and 27 severe patients) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multivariate regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid beta peptide, beta catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe elderly COVID-19 patients. Follow-up analysis using binomial regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies indicated a significantly increased likelihood of developing a severe COVID-19 phenotype, presenting a synergistic effect on worsening COVID-19 outcomes. These findings provide new key insights to explain why elderly patients less favorable outcomes have than young individuals, suggesting new associations of distinct autoantibody levels with disease severity.

Cross‐sectional analysis reveals autoantibody signatures associated with COVID‐19 severity

“…While we found no age effect on the levels of anti-SARS-CoV-2 antibodies, severe SARS-CoV-2 infection induces higher autoantibody titers in elderly patients compared with young patients. Thus, our data point to novel mechanisms involved in the risk intersection of immunosenescence and COVID-19, 44 suggesting that the SARS-CoV-2 infection increases the production of a broad spectrum of autoantibodies linked to autoimmune diseases, particularly in elderly patients. In this context, several age-associated factors, such as chronic inflammation in aging ("inflammageing" 58 ), might promote the production of autoantibodies and the tendency to naturally progress to immune dysregulation of innate 59 and adaptive 60 the increased risk for adverse outcomes in older persons.…”

“…Considering age as a significant predictor of severe outcomes in COVID-19, which was also indicated by Random forest, 44 we investigated the effect of age on the top IgG and IgA autoantibodies stratifying COVID-19 patients according to disease severity. We classified control and disease groups by age (young < 50 and elderly ≥ 50).…”

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

“…The loss of CD8+ T cells in LC appears integral to its autoimmune categorization. Autoimmune risk is directly proportional to both Covid 19 severity and age [11]. Leaky gut syndrome aka dysbiosis is associated with autoimmune disease [12,13,14] and is linked to LC [15,16].…”

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

“…The loss of CD8+ T cells in LC appears integral to its autoimmune categorization. Autoimmune risk is directly proportional to both Covid 19 severity and age [11]. Leaky gut syndrome aka dysbiosis is associated with autoimmune disease [12][13][14] and is linked to LC [15,16].…”