Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

EBioMedicine. 2021 Aug;70:103525. doi: 10.1016/j.ebiom.2021.103525. Epub 2021 Aug 12.


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 S100 family genes (S100A6, S100A8, 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 FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model.

Funding: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.

Keywords: Auranofin; COVID-19; Meta-analysis; Nasal swab/BALF; Prognostic marker; Proteome; Transcriptome.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • COVID-19 / genetics*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cell Line
  • Chlorocebus aethiops
  • Cohort Studies
  • Female
  • HEK293 Cells
  • Humans
  • Inflammation / genetics
  • Inflammation / virology
  • Interleukin-6 / genetics
  • Male
  • Mesocricetus
  • Middle Aged
  • Nasopharynx / pathology
  • Nasopharynx / virology*
  • Pandemics
  • Prognosis
  • Proteome / genetics*
  • RNA, Messenger / genetics
  • SARS-CoV-2 / pathogenicity
  • Transcriptome / genetics*
  • Up-Regulation / genetics
  • Vero Cells
  • Virus Replication / genetics


  • Biomarkers
  • Interleukin-6
  • Proteome
  • RNA, Messenger