Abstract
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.
Highlights
While it is recognized that the host response to infection plays a critical role in determining the severity and outcome of COVID-19, the host microRNA response to SARS-CoV-2 infection is poorly defined
The miRNA signature was shown to be robust in the ferret model of COVID-19 and could distinguish SARS-CoV-2 infection from seasonal influenza A infection. These findings suggest that miRNA profiling may be adopted to improve COVID-19 detection and patient management
Plasma samples were obtained from ten COVID-19 patients and ten age- and gender-matched healthy controls (Table 1)
Summary
Human experimental work was conducted according to the Australian National Health and Medical Research Council Code of Practice. All animal studies were approved by the CSIRO Australian Centre for Disease Preparedness Animal Ethics Committee (document 1990 for SARS-CoV-2, document #1568 for influenza A(H1N1)) and conducted following the Australian National Health and Medical Research Council Code of Practice for the Care and Use of Animals for Scientific Purposes guidelines for housing and care of laboratory animals. All work with live animals was approved by the Institutional Animal Ethics Committee in accordance with guidelines from the Australian Code for the Care and Use of Animals for Scientific Purposes (8th Edition) and compliant with the Victoria State Prevention of Cruelty to Animals Act 1986 and Part 5 of the Prevention of Cruelty to Animals Regulations 2019. Environmental enrichment was provided in the cages during the study
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