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

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.

Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions

“…Effect on ncRNA from Infection Context Investigated Additional Findings [19] miR-766-3p Downregulated COVID-19 patients  miR-766-3p was also downregulated in arthritis patients where patients upregulated IL-6 [20].  miR-766-3p overexpression reduced IL-6 expression in a cell line-immune stimulation model [21].…”

“…Despite the unknowns surrounding immunopathology in COVID-19, strides have already been made to implicate ncRNAs in the regulation of several related immunomodulatory signalling pathways. For instance, a profiling study uncovered several intriguing differential miRNA expression signatures between ten COVID-19 patients and ten healthy control individuals [ 19 ]. First, miR-1275 was significantly downregulated in the COVID-19 patient cohort (Log 2 FC = −5.48), a miRNA implicated in NF-κB IL-6 regulation.…”

“…Therefore, miR-1275 may be a useful biomarker in the identification of an inflammatory state in COVID-19. Further, the most statistically significant differentially expressed miRNA in the COVID-19 profiling study was miR-766-3p, which was downregulated in individuals with COVID-19 [ 19 ]. This miRNA has been previously shown to also be significantly downregulated in the sera of rheumatoid arthritis patients, where patients also exhibit upregulated IL-6 [ 21 ].…”

“…A further comparison in the miRNA profiling study [ 19 ] stratified COVID-19 patients based on the need for oxygenation therapy, and the significant downregulation of miR-766-3p remained in both groups. Patient categorisation based on the need for oxygenation is a common method to classify COVID-19 severity, this aiding in uncovering of the key mechanisms that characterise the worsening of the disease [ 67 , 68 ].…”

The MiR-320 Family Is Strongly Downregulated in Patients with COVID-19 Induced Severe Respiratory Failure

“…Thus, miRNAs play an important role in the control of a large number of cellular processes (e.g., cell proliferation, cell differentiation, and apoptosis) [ 16 ]. In addition to their role in chronic lung disease, miRNAs also modulate an acute phase of inflammation, making them a central key to understanding SARS-CoV-2 infection [ 17 ].…”