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Front Immunol ; 12: 710217, 2021.
Article in English | MEDLINE | ID: covidwho-1555700


Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states.

COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/complications , Cohort Studies , Convalescence , Female , Humans , Male , Middle Aged
EMBO Mol Med ; 13(6): e14045, 2021 06 07.
Article in English | MEDLINE | ID: covidwho-1219070


The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.

COVID-19/pathology , Carrier State/immunology , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/metabolism , COVID-19/immunology , COVID-19/virology , Carrier State/pathology , Carrier State/virology , Cytokines/metabolism , Humans , Monocytes/cytology , Monocytes/immunology , Monocytes/metabolism , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Th17 Cells/cytology , Th17 Cells/immunology , Th17 Cells/metabolism , Transcriptome , Up-Regulation , Vascular Endothelial Growth Factor D/metabolism