Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses
SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes,...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984553/full |
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| author | Xiaoming Sun Xiaoming Sun Ce Gao Ce Gao Ke Zhao Yanhui Yang Yelizaveta Rassadkina Jesse Fajnzylber James Regan Jonathan Z. Li Mathias Lichterfeld Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu Xu G. Yu |
| author_facet | Xiaoming Sun Xiaoming Sun Ce Gao Ce Gao Ke Zhao Yanhui Yang Yelizaveta Rassadkina Jesse Fajnzylber James Regan Jonathan Z. Li Mathias Lichterfeld Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu Xu G. Yu |
| author_sort | Xiaoming Sun |
| collection | DOAJ |
| description | SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients. |
| first_indexed | 2024-04-13T22:05:18Z |
| format | Article |
| id | doaj.art-86599ba6680a44a3b968658fcca916ab |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T22:05:18Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-86599ba6680a44a3b968658fcca916ab2022-12-22T02:27:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.984553984553Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responsesXiaoming Sun0Xiaoming Sun1Ce Gao2Ce Gao3Ke Zhao4Yanhui Yang5Yelizaveta Rassadkina6Jesse Fajnzylber7James Regan8Jonathan Z. Li9Mathias Lichterfeld10Mathias Lichterfeld11Mathias Lichterfeld12Xu G. Yu13Xu G. Yu14Xu G. Yu15Department of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesInfectious Disease Division, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaDepartment of Immunology and Pathogen Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesInfectious Disease Division, Brigham and Women’s Hospital, Boston, MA, United StatesInfectious Disease Division, Brigham and Women’s Hospital, Boston, MA, United StatesInfectious Disease Division, Brigham and Women’s Hospital, Boston, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesInfectious Disease Division, Massachusetts General Hospital, Boston, MA, United StatesInfectious Disease Division, Brigham and Women’s Hospital, Boston, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesInfectious Disease Division, Massachusetts General Hospital, Boston, MA, United StatesInfectious Disease Division, Brigham and Women’s Hospital, Boston, MA, United StatesSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.984553/fullSARS-CoV-2COVID-19viremiaRNAseqinterferon stimulated genessensing |
| spellingShingle | Xiaoming Sun Xiaoming Sun Ce Gao Ce Gao Ke Zhao Yanhui Yang Yelizaveta Rassadkina Jesse Fajnzylber James Regan Jonathan Z. Li Mathias Lichterfeld Mathias Lichterfeld Mathias Lichterfeld Xu G. Yu Xu G. Yu Xu G. Yu Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses Frontiers in Immunology SARS-CoV-2 COVID-19 viremia RNAseq interferon stimulated genes sensing |
| title | Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses |
| title_full | Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses |
| title_fullStr | Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses |
| title_full_unstemmed | Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses |
| title_short | Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses |
| title_sort | immune profiling of sars cov 2 viremic patients reveals dysregulated innate immune responses |
| topic | SARS-CoV-2 COVID-19 viremia RNAseq interferon stimulated genes sensing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.984553/full |
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