Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPFONSECA, Dennyson Leandro M.FILGUEIRAS, Igor SalernoMARQUES, Alexandre H. C.VOJDANI, ElroyHALPERT, GiladOSTRINSKI, YuriBAIOCCHI, Gabriela CrispimPLACA, Desiree RodriguesFREIRE, Paula P.POUR, Shahab ZakiMOLL, GuidoCATAR, RusanLAVI, Yael BublilSILVERBERG, Jonathan I.ZIMMERMAN, JasonCABRAL-MIRANDA, GustavoCARVALHO, Robson F.KHAN, Taj AliHEIDECKE, HaraldDALMOLIN, Rodrigo J. S.LUCHESSI, Andre DucatiOCHS, Hans D.SCHIMKE, Lena F.AMITAL, HowardRIEMEKASTEN, GabrielaZYSKIND, IsraelROSENBERG, Avi Z.VOJDANI, AristoSHOENFELD, YehudaCABRAL-MARQUES, Otavio2023-10-302023-10-302023NPJ AGING, v.9, n.1, article ID 21, 14p, 2023https://observatorio.fm.usp.br/handle/OPI/56004Age 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 ss peptide, ss 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.engrestrictedAccessanticardiolipinprevalenceantibodiescomplexarticleCopyright NATURE PUBL GROUP10.1038/s41514-023-00118-0Geriatrics & Gerontology2731-6068