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PubMed: 38791465 DOI: 10.3390/ijms25105426

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico.

Int J Mol Sci 25(10)

Authors: Lester J Rosario-Rodríguez, Yadira M Cantres-Rosario, Kelvin Carrasquillo-Carrión, Alexandra Rosa-Díaz, Ana E Rodríguez-De Jesús, Verónica Rivera-Nieves, Eduardo L Tosado-Rodríguez, Loyda B Méndez, Abiel Roche-Lima, Jorge Bertrán, Loyda M Meléndez

Affiliations

  • Department of Microbiology and Medical Zoology, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto Rico.
  • Translational Proteomics Center, Research Capacity Core, Center for Collaborative Research in Health Disparities, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto Rico.
  • Integrated Informatics, Research Capacity Core, Center for Collaborative Research in Health Disparities, University of Puerto Rico, Medical Sciences Campus, San Juan 00935, Puerto Rico.
  • Interdisciplinary Studies, Natural Sciences, University of Puerto Rico, Río Piedras Campus, San Juan 00925, Puerto Rico.
  • Department of Science & Technology, Ana G. Mendez University, Carolina 00928, Puerto Rico.
  • Infectious Diseases, Auxilio Mutuo Hospital, San Juan 00919, Puerto Rico.

Abstract

Viral strains, age, and host factors are associated with variable immune responses against SARS-CoV-2 and disease severity. Puerto Ricans have a genetic mixture of races: European, African, and Native American. We hypothesized that unique host proteins/pathways are associated with COVID-19 disease severity in Puerto Rico. Following IRB approval, a total of 95 unvaccinated men and women aged 21-71 years old were recruited in Puerto Rico from 2020-2021. Plasma samples were collected from COVID-19-positive subjects ( = 39) and COVID-19-negative individuals ( = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild ( = 18), moderate ( = 13), and severe ( = 8). Quantitative proteomics was performed in plasma samples using tandem mass tag (TMT) labeling. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer (version 2.5), Limma software (version 3.41.15), and Ingenuity Pathways Analysis (IPA, version 22.0.2). Cytokines were quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 58 differentially expressed proteins. Cadherin-13, which participates in synaptogenesis, was downregulated in severe patients and validated by ELISA. Cytokine immunoassay showed that TNF-α levels decreased with disease severity. This study uncovers potential host predictors of COVID-19 severity and new avenues for treatment in Puerto Ricans.

MeSH

Cytokines, Covid-19, Proteomics, Plasma

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