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J Med Virol ; 93(2): 760-765, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196398


Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 emerged in China in December 2019 and then rapidly spread worldwide. Why COVID-19 patients with the same clinical condition have different outcomes remains unclear. This study aimed to examine the differences in the phenotype and functions of major populations of immune cells between COVID-19 patients with same severity but different outcomes. Four common type adult inpatients with laboratory confirmed COVID-19 from Beijing YouAn Hospital, Capital Medical University were included in this study. The patients were divided into two groups based on whether or not COVID-19 polymerase chain reaction (PCR)-negative conversion occurred within 3 weeks. Peripheral blood samples were collected to compare the differences in the phenotype and functions of major populations of immune cells between the two groups of patients. The result shows that the proportions of CD3+ CD8+ CD38+ HLA-DR+ CD27- effector T killer cells generally declined, whereas that of CD3+ CD4+ CD8+ double-positive T cells (DPTs) increased in the persistently PCR-positive patients. In summary, considering the imbalance between effector T killer cells/CD3+CD4+CD8+ DPTs was a possible key factor for PCR-negative conversion in patients with COVID-19.

Biological Variation, Individual , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/pathology , Natural Killer T-Cells/immunology , SARS-CoV-2/pathogenicity , Adult , Aged , Antigens, CD/genetics , Antigens, CD/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , COVID-19 Testing , Female , Gene Expression , HLA-DR Antigens/genetics , HLA-DR Antigens/immunology , Humans , Immunity, Innate , Immunophenotyping , Lymphocyte Count , Male , Middle Aged , Natural Killer T-Cells/virology , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Severity of Illness Index
Cytometry A ; 97(12): 1217-1221, 2020 12.
Article in English | MEDLINE | ID: covidwho-893217


Several months after the sudden emergence of SARS-CoV-2 and COVID-19, the understanding of the appropriate host immune response to a virus totally unknown of human immune surveillance is still of major importance. By international definition, COVID-19 falls in the scope of septic syndromes (organ dysfunction due to dysregulated host response to an infection) in which immunosuppression is a significant driver of mortality. Sepsis-induced immunosuppression is mostly defined and monitored by the measurement of decreased expression of HLA-DR molecules on circulating monocytes (mHLA-DR). In this interim review, we summarize the first mHLA-DR results in COVID-19 patients. In critically ill patients, results homogenously indicate a decreased mHLA-DR expression, which, along with profound lymphopenia and other functional alterations, is indicative of a status of immunosuppression. © 2020 International Society for Advancement of Cytometry.

COVID-19/immunology , HLA-DR Antigens/immunology , Monocytes/immunology , COVID-19/pathology , COVID-19/virology , Female , Flow Cytometry , HLA-DR Antigens/genetics , Humans , Immune Tolerance/genetics , Male , SARS-CoV-2/pathogenicity
Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694631


Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

Coronavirus Infections/immunology , Myeloid Cells/immunology , Myelopoiesis , Pneumonia, Viral/immunology , Adult , Aged , CD11 Antigens/genetics , CD11 Antigens/metabolism , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/pathology , Female , HLA-DR Antigens/genetics , HLA-DR Antigens/metabolism , Humans , Male , Middle Aged , Myeloid Cells/cytology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Proteome/genetics , Proteome/metabolism , Proteomics , Single-Cell Analysis