International Journal of Molecular Sciences (May 2024)

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico

  • 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

DOI
https://doi.org/10.3390/ijms25105426
Journal volume & issue
Vol. 25, no. 10
p. 5426

Abstract

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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 (n = 39) and COVID-19-negative individuals (n = 56) during acute disease. COVID-19-positive individuals were stratified based on symptomatology as follows: mild (n = 18), moderate (n = 13), and severe (n = 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.

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