Severity-specific immune landscape of COVID-19 revealed by single-cell sequencing
Abstract The Coronavirus disease 2019 (COVID-19) has rapidly become the worst pandemic since the 1918 influenza pandemic. Studies have shown that severe COVID-19 patients have immune dysfunction. To characterize the dysregulated immune response to SARS-CoV-2 infection, we performed a comprehensive a...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-13888-2 |
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| Summary: | Abstract The Coronavirus disease 2019 (COVID-19) has rapidly become the worst pandemic since the 1918 influenza pandemic. Studies have shown that severe COVID-19 patients have immune dysfunction. To characterize the dysregulated immune response to SARS-CoV-2 infection, we performed a comprehensive analysis of scRNA-seq and scV(D)J-seq in peripheral blood mononuclear cells from mild, moderate, and severe patients. We observed that as the severity of the disease increased, several CD8 + T cell subsets and Treg cells continued to decrease, while CD4 + T subsets, natural killer cells and plasma cells continued to increase. Several aberrantly expressed biomarkers associated with SARS-CoV-2 severity were identified. For example, RPS26 was down-regulated, while the ZFP36, IL-32, and IgM genes were up-regulated with increasing disease severity. Functional analysis showed multiple immune-related pathways, such as interleukin-2 and interleukin-10 production pathways, were dysregulated. As the disease severity increased, intercellular interactions fluctuated. Particularly, naive CD8 + T cells regulated memory and activated CD8 + T cells, and the weakening in Treg cells’ regulation of other immune cells was especially obvious. The expression of the MIF signaling pathway, mediated by CD74 + CXCR4, was higher throughout SARS-CoV-2 infection and the intensity of immune cell-cell interactions mediated by TGF-β was enhanced from mild to severe. Subsequently, scV(D)J-seq analysis showed a decreasing trend in the number of clonotypes, repertoire diversity and clonotypes overlap of monoclonal B cell receptor (BCR) and T cell receptor (TCR) as the SARS-CoV-2 progresses. The CDR3 sequence length in COVID-19-specific clonotypes showed a bias towards being longer as the severity of COVID-19 increases. Our findings may provide new clues for understanding COVID-19 immunopathogenesis and help identify optimal biomarkers for new therapeutic strategies. |
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| ISSN: | 2045-2322 |