Abstract
In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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Betacoronavirus / immunology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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COVID-19
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Cohort Studies
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Coronavirus Infections / blood
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Coronavirus Infections / diagnosis
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Coronavirus Infections / immunology*
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Coronavirus Infections / virology
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Female
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / immunology
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GPI-Linked Proteins / metabolism
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Humans
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Interferon Type I / genetics
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Interferon Type I / immunology
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Interferon Type I / metabolism*
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Male
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Middle Aged
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Pandemics
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Pneumonia, Viral / blood
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Pneumonia, Viral / diagnosis
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Pneumonia, Viral / immunology*
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Pneumonia, Viral / virology
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RNA-Seq
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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SARS-CoV-2
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Severity of Illness Index
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Single-Cell Analysis
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD160 protein, human
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GNLY protein, human
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GPI-Linked Proteins
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Interferon Type I
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Receptors, Immunologic