Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3′-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm.
【저자키워드】 COVID-19, SARS-CoV-2, Long COVID, small RNA, circulating-miRNA, 【초록키워드】 viral infection, Cytokine storm, immune response, severe COVID-19, Sequencing, miRNA, cytokine, virus, RNAs, Symptoms, COVID, miRNAs, Viral, Ageusia, immune responses, siRNA, severe cases, Mild, cleavage, plasma, homologous, mechanism, double-stranded RNA, STAT, Analysis, host defense, NSP2, Jak-STAT, candidate gene, Trigger, triggers, Small RNAs, defense mechanism, plasma samples, sequence, product, circulating, Defense, human miRNAs, RNA sequence, Host, nsp4, plasma sample, described, conserved, detectable, the disease, events, reduced, convalescent COVID-19 patient, human miRNA, transcriptional gene silencing, 【제목키워드】 detection, change, with COVID-19,