Identifying microRNA expression alterations in erythrocytes, lymphocytes, and monocytes during severe COVID-19

A significant portion of the fatal outcomes during COVID-19 have been traced mainly to cytokine storm, the uncontrolled hyperactivation of the immune system. During a SARS-CoV-2 infection, the blood plasma levels of microRNAs (miRNAs), a class of short regulatory RNAs, get significantly changed. However, it still remains unknown how the levels and characteristics of these molecules are altered in various blood cells during severe COVID-19. The aim of this research was to compare the microRNA levels in erythro cytes, monocytes, and lymphocytes in normal blood cells and those in patients with severe COVID-19-induced by cytokine storm. Erythrocytes and monocytes (five healthy donors and five patients with severe COVID-19) and lymphocytes (four healthy donors and four patients with severe COVID-19) were obtained by fluores cence-activated cell sorting. RNA was isolated from the obtained cells, and next-generation short RNA se quencing was performed. Both the known miRNAs and the novel miRNAs whose expression had changed in severe COVID-19 were analyzed and identified. In the erythrocytes, seven miRNAs had changed expres sions (five downregulated; two upregulated); all 13 miRNAs were upregulated in lymphocytes; in monocytes, 11 miRNAs were downregulated and three miRNAs were upregulated. An analysis of the novel miRNAs showed that three, previously unknown miRNAs, were downregulated in lymphocytes and one was upregu lated. In monocytes and erythrocytes, no novel, differentially expressed miRNAs were detected. Additionally, we analyzed the signaling pathways altered by miRNAs by performing a miRNA enrichment analysis (MIEAA) using the Gene Ontology miRNA target database (miRTarBase). We observed that in lymphocytes, four pathways were significantly (Q-value < 0.05) enriched and 339 were depleted; in monocytes, 118 path ways were enriched and six were depleted. No significantly altered signaling pathways were detected in erythrocytes.