Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients
SUMMARY Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.HIGHLIGHTS <jats:list list-type="bullet">Large-scale scRNA-seq analysis depicts the immune landscape of COVID-19Lymphopenia and active T and B cell responses coexist and are shaped by age and sexSARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responsesCytokine storms with systemic S100A8/A9 are associated with COVID-19 severity.
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 25. Nov. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ren, Xianwen [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.1101/2020.10.29.360479 |
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| funding: |
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| PPN (Katalog-ID): |
XBI019233167 |
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| 520 | |a SUMMARY Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.HIGHLIGHTS <jats:list list-type="bullet">Large-scale scRNA-seq analysis depicts the immune landscape of COVID-19Lymphopenia and active T and B cell responses coexist and are shaped by age and sexSARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responsesCytokine storms with systemic S100A8/A9 are associated with COVID-19 severity | ||
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