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.
【저자키워드】 severe acute respiratory syndrome coronavirus 2, T cell response, T-CD8 lymphocytes flow cytometric immunophenotyping, Th lymphocytes, severe coronavirus disease 2019, 【초록키워드】 COVID-19, T cells, SARS-COV-2 infection, severity, Th1, Th17, outcome, CD8, Peripheral blood, lymphopenia, lymphocyte, T cell, immune profiling, Patient, donors, virus infection, Adaptive immune response, virus load, Critical, HLA-DR, CD38, CD8+ T cell, Blood, marker, high-risk population, Frequency, Analysis, Inflammatory, COVID-19 patient, T cells response, innate response, T helper, Activation, Factor, T lymphocyte, CD4+, Express, multiparametric flow cytometry, CD8+, effective, Cell, decrease, Th cell, performed, affected, characterized, subset, explain, Th1 cell, Th1/Th17, 【제목키워드】 COVID-19, Th1, clinical, negative, Increased, Undifferentiated, Strong, Frequently,