Transcriptomic analysis of differential expression between surviving and nonsurviving patients infected by the SARS-CoV-2 Delta variant.

For a more precise understanding of the course of the pathological process in patients with severe COVID-19, it is necessary to continue the search for factors that affect the course of the pathological process and the possibility of a favorable outcome in critically ill patients. Comparative RNA-seq analysis of the transcriptome of peripheral blood mononuclear cell (PBMCs) in patients with a severe clinical course of COVID-19 caused by the SARS-CoV-2 Delta strain revealed a number of differentially expressed genes that distinguish patients with different clinical outcomes (survivors vs. nonsurvivors) in the period of 30 days after admission to the hospital. Most of them are associated with the "negative regulation of viral process" and "negative regulation of immune response" clusters. Moreover, in surviving patients, there is increased expression of the key genes C1QB, C1QA, ISG15, SERPING1, VSIG4, KLRD1, TRPM4, and HFE incorporated in these clusters. Among these key genes, the ISG15 gene, which links several clusters of gene ontology enrichments and encodes an interferon-induced ubiquitin-like protein, deserves special attention. Its product, ISG15, is known to be a primary substrate for SARS-CoV-2 protease PLpro, which plays a role in counteracting hosts' antiviral mechanisms.