Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach
Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and 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 severity (71 mild, 61 moderate, and 27 with severe symptoms) 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. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis 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 COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.
Fonseca, Dennyson Leandro; Filgueiras, Igor Salerno; Marques, Alexandre H.; Vojdani, Elroy; Halpert, Gilad; Ostrinski, Yuri; Baiocchi, Gabriela Crispim; Plaça, Desirée Rodrigues; Freire, Paula P.; Pour, Shahab Zaki; Moll, Guido; Catar, Rusan; Lavi, Yael Bublil; Silverberg, Jonathan I.; Zimmerman, Jason; Cabral-Miranda, Gustavo; Carvalho, Robson F.; Khan, Taj Ali; Heidecke, Harald; Dalmolin, Rodrigo J.; Luchessi, Andre Ducati; Ochs, Hans D.; Schimke, Lena F.; Amital, Howard; Riemekasten, Gabriela; Zyskind, Israel; Rosenberg, Avi Z.; Vojdani, Aristo; Shoenfeld, Yehuda; and Cabral-Marques, Otavio, "Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach" (2023). GW Authored Works. Paper 3210.