Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection

PLoS Pathog. 2021 Jul 28;17(7):e1009759. doi: 10.1371/journal.ppat.1009759. eCollection 2021 Jul.


The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ten COVID-19 patients sampled longitudinally and ten age and gender matched healthy donors. We observed 55 miRNAs that were altered in COVID-19 patients during early-stage disease, with the inflammatory miR-31-5p the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-423-5p, miR-23a-3p and miR-195-5p) independently classified COVID-19 cases with an accuracy of 99.9%. In a ferret COVID-19 model, the three-miRNA signature again detected SARS-CoV-2 infection with 99.7% accuracy, and distinguished SARS-CoV-2 infection from influenza A (H1N1) infection and healthy controls with 95% accuracy. Distinct miRNA profiles were also observed in COVID-19 patients requiring oxygenation. This study demonstrates that SARS-CoV-2 infection induces a robust host miRNA response that could improve COVID-19 detection and patient management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • COVID-19 / blood
  • COVID-19 / diagnosis*
  • COVID-19 / genetics*
  • COVID-19 Testing / methods*
  • Case-Control Studies
  • Diagnosis, Differential
  • Disease Models, Animal
  • Female
  • Ferrets
  • Gene Expression
  • Host Microbial Interactions / genetics
  • Humans
  • Influenza A Virus, H1N1 Subtype
  • Longitudinal Studies
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Orthomyxoviridae Infections / diagnosis
  • Orthomyxoviridae Infections / genetics
  • Pandemics
  • SARS-CoV-2*
  • Supervised Machine Learning


  • MIRN195 microRNA, human
  • MIRN23a microRNA, human
  • MIRN423 microRNA, human
  • MicroRNAs

Grant support

This work was supported by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) ( (C.R.S., grant number N/A). We acknowledge funding from the Coalition for Epidemic Preparedness Innovations (CEPI) ( (S.S.V., grant number N/A) for supporting ferret COVID-19 studies. S.S.V. is grateful for support from Australian Department of Finance (grant number N/A) and CSIRO Future Science Platforms (grant number N/A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.