Identification Of Covid-19 Prognostic Markers And Therapeutic Targets Through Meta-Analysis And Validation Of Omics Data From Nasopharyngeal Samples

Background: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets.Methods: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model.Findings: The meta-analysis and validation in the COVID-19 cohort revealed 5100 family genes (S100A6, S100AB, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs.Interpretation: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDAapproved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. (C) 2021 The Author( s). Published by Elsevier B.V.