Role of lymphoid lineage cells aberrantly expressing alarmins S100A8/A9 in determining the severity of COVID-19

• Published in: Genes & genomics 2023, 45(3), , pp.337-346
• Main Authors: Lee, Joongho, Kim, Hanbyeol, Kim, Minsoo, Yoon, Seokhyun, Lee, Sanghun
• Format: Article
• Language: English
• Subjects: Alarmins; Analysis; Animal Genetics and Genomics; Biomedical and Life Sciences; Calgranulin A - metabolism; Coronaviruses; COVID-19; Cytokine storm; Cytokines; Cytokines - metabolism; Development and progression; Health aspects; Human Genetics; Humans; Infection; Infections; Inflammation; Innate immunity; Interferon; Killer Cells, Natural - metabolism; Leukocytes (neutrophilic); Life Sciences; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoid cells; Medical research; Medicine, Experimental; Microbial Genetics and Genomics; Monocytes; Myeloid cells; Plant Genetics and Genomics; Research Article; RNA; TLR4 protein; Toll-like receptors; 생물학
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-022-01285-2

Background Alarmins S100A8 and S100A9 are recognized as hallmarks of severe COVID-19 and are primarily produced in myeloid cells, such as monocytes and neutrophils. As single-cell RNA-sequencing (scRNA-seq) data from patients with COVID-19 revealed the expression of S100A8/A9 in lymphoid cells in patients with severe COVID-19. Objective We investigated the characteristics of lymphoid cells expressing S100A8/A9 in COVID-19 patients. Methods Publicly available scRNA-seq data from patients with mild (N = 12) or severe (N = 7) COVID-19 were reanalyzed. The data were further divided into the following two groups based on the time of sample collection (from infection-onset): within 6 days (early phase) and after 6 days (late phase). Differential expression and gene set enrichment analyses were performed between S100A8/A9 High and S100A8/A9 Low lymphoid cells. Finally, cell-cell interaction analysis was performed to investigate the role of lymphoid cells expressing high levels of S100A8/A9 in COVID-19. Results S100A8/A9 overexpression was observed in lymphoid cells, including B cells, T cells, and NK cells, in patients with severe COVID-19 (compared to patients with mild COVID-19). Cells exhibiting strong interferon/cytokine responses were found to be associated with the severity of COVID-19. Furthermore, differences in S100A8/A9-TLR4/RAGE interactions were confirmed between patients with severe and mild disease. Conclusions Lymphoid cells overexpressing S100A8/A9 contribute to the dysregulation of the innate immune response in patients with severe COVID-19, specifically during the early phase of infection. This study fosters a better understanding of the hyper-induction of pro-inflammatory cytokine expression and the generation of a cytokine storm in response to COVID-19 infection.