Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
1.
Nat Immunol ; 23(1): 23-32, 2022 01.
Article in English | MEDLINE | ID: covidwho-1585822

ABSTRACT

Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates1-6. Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c+ natural killer (NK) cells and CD4+ T effector cells during acute COVID-19. The mucosal proinflammatory populations positively associated with peripheral blood human leukocyte antigen (HLA)-DRlow monocytes, CD38+PD1+CD4+ T effector (Teff) cells and plasmablasts. However, there was no general lymphopenia in nasal mucosa, unlike in peripheral blood. Moreover, nasal neutrophils negatively associated with oxygen saturation levels in blood. Following convalescence, nasal immune cells mostly normalized, except for CD127+ granulocytes and CD38+CD8+ tissue-resident memory T cells (TRM). SARS-CoV-2-specific CD8+ T cells persisted at least 2 months after viral clearance in the nasal mucosa, indicating that COVID-19 has both transient and long-term effects on upper respiratory tract immune responses.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Nasopharynx/immunology , Nose/cytology , Respiratory Mucosa/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/pathology , Granulocytes/immunology , HLA-DR Antigens/metabolism , Humans , Killer Cells, Natural/immunology , Monocytes/immunology , Nasopharynx/cytology , Nasopharynx/virology , Neutrophils/immunology , Nose/immunology , Nose/virology , Prospective Studies , Respiratory Mucosa/cytology , Respiratory Mucosa/virology
2.
Front Immunol ; 12: 739757, 2021.
Article in English | MEDLINE | ID: covidwho-1505515

ABSTRACT

Coronavirus disease 2019 (COVID-19) exhibits a sex bias with males showing signs of more severe disease and hospitalizations compared with females. The mechanisms are not clear but differential immune responses, particularly the initial innate immune response, between sexes may be playing a role. The early innate immune responses to SARS-CoV-2 have not been studied because of the gap in timing between the patient becoming infected, showing symptoms, and getting the treatment. The primary objective of the present study was to compare the response of dendritic cells (DCs) and monocytes from males and females to SARS-CoV-2, 24 h after infection. To investigate this, peripheral blood mononuclear cells (PBMCs) from healthy young individuals were stimulated in vitro with the virus. Our results indicate that PBMCs from females upregulated the expression of HLA-DR and CD86 on pDCs and mDCs after stimulation with the virus, while the activation of these cells was not significant in males. Monocytes from females also displayed increased activation than males. In addition, females secreted significantly higher levels of IFN-α and IL-29 compared with males at 24 h. However, the situation was reversed at 1 week post stimulation and males displayed high levels of IFN-α production compared with females. Further investigations revealed that the secretion of CXCL-10, a chemokine associated with lung complications, was higher in males than females at 24 h. The PBMCs from females also displayed increased induction of CTLs. Altogether, our results suggest that decreased activation of pDCs, mDCs, and monocytes and the delayed and prolonged IFN-α secretion along with increased CXCL-10 secretion may be responsible for the increased morbidity and mortality of males to COVID-19.


Subject(s)
COVID-19/immunology , Dendritic Cells/immunology , Leukocytes, Mononuclear/immunology , SARS-CoV-2/physiology , Adaptive Immunity , Adult , Chemokine CXCL1/metabolism , Female , HLA-DR Antigens/metabolism , Healthy Volunteers , Humans , Immunity, Innate , Interferon-gamma/metabolism , Male , Middle Aged , Sex Characteristics , Up-Regulation , Young Adult
4.
Nat Immunol ; 22(1): 74-85, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065902

ABSTRACT

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Peptides/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Viral Vaccines/immunology , COVID-19/prevention & control , COVID-19/virology , Cross Reactions/immunology , HLA-DR Antigens/immunology , HLA-DR Antigens/metabolism , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class I/metabolism , Humans , Immunologic Memory/immunology , SARS-CoV-2/physiology , T-Lymphocytes/metabolism , Viral Vaccines/administration & dosage
5.
Front Immunol ; 11: 596553, 2020.
Article in English | MEDLINE | ID: covidwho-979020

ABSTRACT

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Helper-Inducer/immunology , Th1 Cells/immunology , ADP-ribosyl Cyclase 1/immunology , ADP-ribosyl Cyclase 1/metabolism , Aged , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , COVID-19/virology , Cell Differentiation/immunology , Female , HLA-DR Antigens/immunology , HLA-DR Antigens/metabolism , Humans , Lymphocyte Activation/immunology , Male , Middle Aged , Prospective Studies , SARS-CoV-2/physiology , T-Lymphocytes, Helper-Inducer/metabolism , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism
6.
Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694631

ABSTRACT

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.


Subject(s)
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
SELECTION OF CITATIONS
SEARCH DETAIL
...