SARS-CoV-2 has had a serious impact on the world. In this study, small RNAs from the blood of COVID-19 patients with moderate or severe symptoms were extracted for high-throughput sequencing and analysis. Interestingly, the levels of a special group of tRNA-derived small RNAs (tsRNAs) were found to be dramatically upregulated after SARS-CoV-2 infection, particularly in COVID-19 patients with severe symptoms. In particular, the 3'CCA tsRNAs from Gly-tRNA were highly consistent with the inflammation indicator C-reactive protein (CRP). In addition, we found that the majority of significantly changed microRNAs (miRNAs) were associated with endoplasmic reticulum (ER)/unfolded protein response (UPR) sensors, which may lead to the induction of proinflammatory cytokine and immune responses. This study found that SARS-CoV-2 infection caused significant changes in the levels of stress-associated small RNAs in patient blood and their potential functions. Our research revealed that the cells of COVID-19 patients undergo tremendous stress and respond, which can be reflected or regulated by sncRNAs, thus providing potential thought for therapeutic intervention in COVID-19 by modulating small RNA levels or activities.
Graphical Abstract
Analysis of small RNA sequencing data revealed that tsRNA and microRNA levels in the blood of COVID-19 patients have undergone drastic changes, and these changes are related to stress responses. It implies that small RNA has the potential to be a drug or therapeutic target for COVID-19.