tetano
Editor, Senior Moderator
NPJ Aging
. 2023 Aug 24;9(1):21.
doi: 10.1038/s41514-023-00118-0. Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach
Dennyson Leandro M Fonseca[SUP] #[/SUP][SUP] 1 [/SUP], Igor Salerno Filgueiras[SUP] #[/SUP][SUP] 2 [/SUP], Alexandre H C Marques[SUP] 2 [/SUP], Elroy Vojdani[SUP] 3 [/SUP], Gilad Halpert[SUP] 4 5 6 [/SUP], Yuri Ostrinski[SUP] 4 5 6 [/SUP], Gabriela Crispim Baiocchi[SUP] 2 [/SUP], Desirée Rodrigues Plaça[SUP] 7 [/SUP], Paula P Freire[SUP] 2 [/SUP], Shahab Zaki Pour[SUP] 8 [/SUP], Guido Moll[SUP] 9 [/SUP], Rusan Catar[SUP] 9 [/SUP], Yael Bublil Lavi[SUP] 10 [/SUP], Jonathan I Silverberg[SUP] 11 [/SUP], Jason Zimmerman[SUP] 12 [/SUP], Gustavo Cabral-Miranda[SUP] 2 [/SUP], Robson F Carvalho[SUP] 13 [/SUP], Taj Ali Khan[SUP] 14 [/SUP], Harald Heidecke[SUP] 15 [/SUP], Rodrigo J S Dalmolin[SUP] 16 17 [/SUP], Andre Ducati Luchessi[SUP] 18 [/SUP], Hans D Ochs[SUP] 19 [/SUP], Lena F Schimke[SUP] 2 [/SUP], Howard Amital[SUP] 4 5 20 21 [/SUP], Gabriela Riemekasten[SUP] 22 [/SUP], Israel Zyskind[SUP] #[/SUP][SUP] 12 23 [/SUP], Avi Z Rosenberg[SUP] #[/SUP][SUP] 24 [/SUP], Aristo Vojdani[SUP] #[/SUP][SUP] 25 26 [/SUP], Yehuda Shoenfeld[SUP] #[/SUP][SUP] 5 [/SUP], Otavio Cabral-Marques[SUP] #[/SUP][SUP] 27 28 29 30 31 32 33 [/SUP]
Affiliations
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.
. 2023 Aug 24;9(1):21.
doi: 10.1038/s41514-023-00118-0. Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach
Dennyson Leandro M Fonseca[SUP] #[/SUP][SUP] 1 [/SUP], Igor Salerno Filgueiras[SUP] #[/SUP][SUP] 2 [/SUP], Alexandre H C Marques[SUP] 2 [/SUP], Elroy Vojdani[SUP] 3 [/SUP], Gilad Halpert[SUP] 4 5 6 [/SUP], Yuri Ostrinski[SUP] 4 5 6 [/SUP], Gabriela Crispim Baiocchi[SUP] 2 [/SUP], Desirée Rodrigues Plaça[SUP] 7 [/SUP], Paula P Freire[SUP] 2 [/SUP], Shahab Zaki Pour[SUP] 8 [/SUP], Guido Moll[SUP] 9 [/SUP], Rusan Catar[SUP] 9 [/SUP], Yael Bublil Lavi[SUP] 10 [/SUP], Jonathan I Silverberg[SUP] 11 [/SUP], Jason Zimmerman[SUP] 12 [/SUP], Gustavo Cabral-Miranda[SUP] 2 [/SUP], Robson F Carvalho[SUP] 13 [/SUP], Taj Ali Khan[SUP] 14 [/SUP], Harald Heidecke[SUP] 15 [/SUP], Rodrigo J S Dalmolin[SUP] 16 17 [/SUP], Andre Ducati Luchessi[SUP] 18 [/SUP], Hans D Ochs[SUP] 19 [/SUP], Lena F Schimke[SUP] 2 [/SUP], Howard Amital[SUP] 4 5 20 21 [/SUP], Gabriela Riemekasten[SUP] 22 [/SUP], Israel Zyskind[SUP] #[/SUP][SUP] 12 23 [/SUP], Avi Z Rosenberg[SUP] #[/SUP][SUP] 24 [/SUP], Aristo Vojdani[SUP] #[/SUP][SUP] 25 26 [/SUP], Yehuda Shoenfeld[SUP] #[/SUP][SUP] 5 [/SUP], Otavio Cabral-Marques[SUP] #[/SUP][SUP] 27 28 29 30 31 32 33 [/SUP]
Affiliations
- PMID: 37620330
- DOI: 10.1038/s41514-023-00118-0
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.