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. Author summary 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 (miRNA) response to SARS-CoV-2 infection is poorly defined. Here we have used next-generation sequencing and bioinformatics to profile circulating miRNAs in 10 COVID-19 patients that were sampled longitudinally over time. COVID-19 was associated with altered expression of 55 plasma miRNAs, with miR-776-3p and miR-1275 among the most strongly down-regulated, and miR-4742-3p, miR-31-5p and miR-3215-3p the most up-regulated. An artificial intelligence methodology was used to identify a miRNA signature, consisting of miR423-5p, miR-23a-3p, miR-195-5p, which could independently classify COVID-19 patients from healthy controls with 99.9% accuracy. When applied to the ferret model of COVID-19, the same signature classified COVID-19 cases with 99.8% accuracy and could distinguish between COVID-19 and influenza A(H1N1) infection with >95% accuracy. In summary this study profiles the host miRNA response to COVID-19 and suggests that the measurement of select host molecules may have potential to independently detect disease cases.
【초록키워드】 COVID-19, Influenza, SARS-COV-2 infection, severity, artificial intelligence, microRNA, bioinformatics, miRNA, viral pathogenesis, Infection, host response, outcome, influenza A, miRNAs, Viral, Accuracy, management, Next-generation sequencing, Patient, plasma, H1N1, Patient management, disease, expression, Critical, COVID-19 patients, Inflammatory, COVID-19 cases, COVID-19 patient, Oxygenation, healthy donors, profile, healthy control, COVID-19 case, healthy controls, artificial intelligence methodology, circulating miRNAs, host miRNA, host-encoded microRNA, miR-1275, miR-195-5p, miR-23a-3p, miR-3215-3p, miR-423-5p, miR-4742-3p, miR-776-3p, miR423, miR423-5p, miRNA signature, Supervised machine learning analysis, while, Host, host miRNA response, robust, IMPROVE, defined, identify, was used, detect, applied, induce, upregulated, up-regulated, down-regulated, age and gender, circulating miRNA, host molecule, machine learning analysis, miR-31-5p, miRNA profile, 【제목키워드】 microRNA, expression, COVID-19 patient, Altered,