Plasma proteins associated with COVID-19 in unvaccinated and vaccinated Puerto Ricans

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 and that vaccination reverts these proteins' dysregulation. Following IRB approval, 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). An additional subgroup of vaccinated participants before COVID-19 infection (n=11) was compared to vaccinated COVID-19-negative individuals (n=15). Quantitative proteomics was performed using Tandem Mass Tag (TMT) labeling in plasma samples. Labeled peptides were subjected to LC/MS/MS and analyzed by Proteome Discoverer, Limma software, and Ingenuity Pathways Analysis (IPA). Cytokines were also quantified using a human cytokine array. Proteomics analyses of severely affected COVID-19-positive individuals revealed 2 upregulated and 54 downregulated proteins. In vaccinated individuals we did not find downregulated proteins. Cytokine immunoassay showed that IL-1Ra, IP-10, and TNF-⍺ levels increased while PDGF decreased with COVID-19 in unvaccinated individuals while only IP-10 was upregulated in vaccinated individuals. This study demonstrates that proteomics studies help uncover potential host predictors of COVID-19 severity in Puerto Ricans modulated by vaccination.

Supported in part by UPR COVID-19 Emergency Funds, National Institutes of Health National Institute of General Medical Sciences (NIGMS), PR-INBRE-Institutional Developmental Award (IDEA) P20GM103475, Research Infrastructure Core components – National Institute of Minority Health and Health Disparities (NIMHHD) U54MD007600, Translational Proteomics Center, and Bioinformatics and Health Informatics, "D-SPAN"- F99NS11345 and K00NS11345.