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

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Fonseca, Dennyson Leandro M. ; Filgueiras, Igor Salerno ; Marques, Alexandre H. C. ; Vojdani, Elroy ; Halpert, Gilad ; Ostrinski, Yuri ; Baiocchi, Gabriela Crispim ; Placa, Desiree 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. S. ; Luchessi, Andre Ducati ; Ochs, Hans D. ; Schimke, Lena F. ; Amital, Howard ; Riemekasten, Gabriela ; Zyskind, Israel ; Rosenberg, Avi Z. ; Vojdani, Aristo ; Shoenfeld, Yehuda ; Cabral-Marques, Otavio
Total Authors: 30
Document type: Journal article
Source: NPJ AGING; v. 9, n. 1, p. 14-pg., 2023-08-24.
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 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. (AU)

FAPESP's process: 20/11710-2 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with Dengue
Grantee:Desirée Rodrigues Plaça
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 20/09146-1 - Systemic and integrative analysis of molecular mechanisms associated with immunoregulation in patients with COVID-19
Grantee:Paula Paccielli Freire-Barguil
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 20/16246-2 - Holistic characterization of T cell exhaustion in patients with Zika
Grantee:Dennyson Leandro Mathias da Fonseca
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
Grantee:Otávio Cabral Marques
Support Opportunities: Scholarships in Brazil - Young Researchers
FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
Grantee:Otávio Cabral Marques
Support Opportunities: Regular Research Grants
FAPESP's process: 20/07972-1 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
Grantee:Gabriela Crispim Baiocchi
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
Grantee:Otávio Cabral Marques
Support Opportunities: Research Grants - Young Investigators Grants