COVID-19 plasma deep proteome reveals distinct signatures in severe patients

Abstract Prognosis and management of COVID-19 severity is a challenge even after months of the pandemic. Host plasma proteome alterations carry insights into the physiological alterations in response to the infection. Here we employed a mass spectrometry-based label-free quantitative proteomics approach to study alteration in plasma proteome in a cohort of 73 patients (20 COVID negative, 18 non-severe, and 33 severe) to understand the disease dynamics for addressing this challenge. Of the 1200 proteins detected in the patient plasma, 38 proteins were differentially expressed between non-severe and severe groups. The host proteins such as Angiotensinogen, apolipoprotein B, SERPINA3, SERPING1, and Fibrinogen gamma chain identified in LFQ analysis were further validated using targeted mass spectrometry assay. Utilizing our proteomics dataset, we identified multiple drugs that could inhibit the upregulated proteins involved in disease pathogenesis of these 2 FDA-approved drugs Selinexor and Ponatinib, which showed promise of being re-purposed for potential therapeutics of COVID-19. Plasma proteome identified significant dysregulation in the pathways related to peptidase activity, regulated exocytosis, blood coagulation, complement activation, leukocyte activation involved in immune response, and response to glucocorticoid biological processes during severe SARS-CoV-2 infection. Further, the results suggest that COVID-19 severity can be prognosticated using specific biomarkers of severity, and few of these proteins are excellent targets for re-purposed drugs.