PT - JOURNAL ARTICLE AU - Noa C. Harriott AU - Amy L. Ryan TI - Proteomic profiling identifies biomarkers of COVID-19 severity AID - 10.1101/2022.11.29.518411 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.11.29.518411 4099 - http://biorxiv.org/content/early/2022/11/30/2022.11.29.518411.short 4100 - http://biorxiv.org/content/early/2022/11/30/2022.11.29.518411.full AB - SARS-CoV-2 infection remains a major public health concern, particularly for the aged and those individuals with co-morbidities at risk for developing severe COVID-19. Understanding the pathogenesis and biomarkers associated with responses to SARS-CoV-2 infection remain critical components in developing effective therapeutic approaches, especially in cases of severe and long-COVID-19. In this study blood plasma protein expression was compared in subjects with mild, moderate, and severe COVID-19 disease. Evaluation of an inflammatory protein panel confirms upregulation of proteins including TNFβ, IL-6, IL-8, IL-12, already associated with severe cytokine storm and progression to severe COVID-19. Importantly, we identify several proteins not yet associated with COVID-19 disease, including mesothelin (MSLN), that are expressed at significantly higher levels in severe COVID-19 subjects. In addition, we find a subset of markers associated with T-cell and dendritic cell responses to viral infection that are significantly higher in mild cases and decrease in expression as severity of COVID-19 increases, suggesting that an immediate and effective activation of T-cells is critical in modulating disease progression. Together, our findings identify new targets for further investigation as therapeutic approaches for the treatment of SARS-CoV-2 infection and prevention of complications of severe COVID-19.Competing Interest StatementThe authors have declared no competing interest.