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Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.


ABSTRACT: 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.

SUBMITTER: Fonseca DLM 

PROVIDER: S-EPMC10449916 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.

Fonseca Dennyson Leandro M DLM   Filgueiras Igor Salerno IS   Marques Alexandre H C AHC   Vojdani Elroy E   Halpert Gilad G   Ostrinski Yuri Y   Baiocchi Gabriela Crispim GC   Plaça Desirée Rodrigues DR   Freire Paula P PP   Pour Shahab Zaki SZ   Moll Guido G   Catar Rusan R   Lavi Yael Bublil YB   Silverberg Jonathan I JI   Zimmerman Jason J   Cabral-Miranda Gustavo G   Carvalho Robson F RF   Khan Taj Ali TA   Heidecke Harald H   Dalmolin Rodrigo J S RJS   Luchessi Andre Ducati AD   Ochs Hans D HD   Schimke Lena F LF   Amital Howard H   Riemekasten Gabriela G   Zyskind Israel I   Rosenberg Avi Z AZ   Vojdani Aristo A   Shoenfeld Yehuda Y   Cabral-Marques Otavio O  

npj aging 20230824 1


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 associa  ...[more]

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