Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

In this study, we sought to identify circulating microRNA (miRNA) signatures associated with COVID-19 severity and outcome through small RNA-sequencing of serum samples from 89 COVID-19 patients and 45 healthy controls. As results, a set of miRNAs associated with lung disease, vascular damage and inflammation were upregulated in serum of COVID-19 patients vs controls, while miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis and stress response were downregulated. In addition, patients with severe COVID-19 vs mild or moderate disease had a circulating miRNA signature associated with sepsis, hearth failure, tissue fibrosis, inflammation, and impairment of type I IFN and antiviral responses. A subset of the differentially expressed miRNAs predicted ICU admission, sequelae and mortality in COVID-19 patients. Investigation of the differentially expressed circulating miRNAs in relevant human cell types in vitro showed that some of these miRNAs were modulated directly by SARS-CoV-2 infection or indirectly by type I IFN stimulation. The study population included 89 COVID-19 patients, who were admitted at the IRCCS Sacro Cuore Don Calabria hospital, Negrar, Verona, Italy, in the period between May 2020 and December 2020. Inclusion criteria for the study were age ≥18 years and diagnosis of SARS-CoV-2 infection confirmed by molecular testing on nasopharyngeal swabs. As exclusion criteria, pregnant women were not enrolled. Disease severity was scored into mild, moderate, and severe at the time of hospital admission according to World Health Organization COVID-19 disease severity classification criteria 67. Peripheral blood samples were collected at the time of hospital admission, and before starting medications. Sera were separated from whole blood by centrifugation for 15 min at 3,000 rpm at 4 °C and stored at -80 °C until processing. Serum samples from 45 healthy volunteers collected before September 2019 and stored at -80 °C were used as negative control group.