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KMID : 0381120230450030337
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Genes and Genomics
2023 Volume.45 No. 3 p.337 ~ p.346
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Role of lymphoid lineage cells aberrantly expressing alarmins S100A8/A9 in determining the severity of COVID-19
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Lee Joong-Ho
Kim Han-Byeol
Kim Min-Soo
Yoon Seok-Hyun
Lee Sang-Hun
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Abstract
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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/A9High and S100A8/A9Low 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.
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KEYWORD
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COVID-19, Single-cell RNA-sequencing, S100A8/A9, Lymphoid cells
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