Transcriptomics of severe COVID-19

Currently, identifying biomarkers that can reliably predict the risk of developing severe COVID-19, potentially leading to fatal outcomes, remains a critical challenge. Studying the pathogenetic mechanisms underlying the progression from moderate to severe disease through blood transcriptome analysis enables the identification of differentially expressed genes (DEGs), which may serve as potential prognostic biomarkers of disease severity and as novel therapeutic targets for managing COVID-19 complications. In this review, we have summarized and analyzed studies that compared gene expression profiles between moderate and severe COVID-19 cases using bulk RNA sequencing of blood cell samples. Based on the results of five studies, five commonly and significantly differentially expressed genes were identified (CD177, PPARG, PCOLCE2, SLC51A and ADAMTS2), and their potential roles in the progression to severe COVID-19 are discussed. Functional enrichment analysis was performed, and shared pathways associated with severe COVID-19 were identified, including neutrophil degranulation, interleukin signaling, collagen biosynthesis, and suppression of adaptive and NK cell-mediated immune responses. Additionally, single-cell RNA sequencing (scRNA-seq) studies were reviewed, comparing moderate and severe cases, supporting some of the bulk RNA-seq findings. Due to the limited overlap of data in the reviewed articles, one section of this review focuses on the study designs, including analytical tools, sample collection protocols, and criteria used to define comparison groups. Transcriptomic analysis of the COVID-19 severe form reveals both cellular and molecular mechanisms of the immune response, the dysregulation of which can lead to the development of severe manifestations. RNA-markers seem to be promising predictors of the severity of COVID-19. At the same time, other omics technologies can fill in the gaps in understanding the characteristics of severe COVID-19 and identify mechanisms of disease progression to develop approaches for COVID-19 prevention and treatment.

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