TY - JOUR
T1 - Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age
T2 - a systems biology approach
AU - Fonseca, Dennyson Leandro M.
AU - Filgueiras, Igor Salerno
AU - Marques, Alexandre H.C.
AU - Vojdani, Elroy
AU - Halpert, Gilad
AU - Ostrinski, Yuri
AU - Baiocchi, Gabriela Crispim
AU - Plaça, Desirée Rodrigues
AU - Freire, Paula P.
AU - Pour, Shahab Zaki
AU - Moll, Guido
AU - Catar, Rusan
AU - Lavi, Yael Bublil
AU - Silverberg, Jonathan I.
AU - Zimmerman, Jason
AU - Cabral-Miranda, Gustavo
AU - Carvalho, Robson F.
AU - Khan, Taj Ali
AU - Heidecke, Harald
AU - Dalmolin, Rodrigo J.S.
AU - Luchessi, Andre Ducati
AU - Ochs, Hans D.
AU - Schimke, Lena F.
AU - Amital, Howard
AU - Riemekasten, Gabriela
AU - Zyskind, Israel
AU - Rosenberg, Avi Z.
AU - Vojdani, Aristo
AU - Shoenfeld, Yehuda
AU - Cabral-Marques, Otavio
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85177100438&partnerID=8YFLogxK
U2 - 10.1038/s41514-023-00118-0
DO - 10.1038/s41514-023-00118-0
M3 - Journal articles
AN - SCOPUS:85177100438
SN - 2731-6068
VL - 9
JO - npj Aging
JF - npj Aging
IS - 1
M1 - 21
ER -