Background The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR + CD38 + CD8 + T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38 + HLA-DR + CD8 + T population was reported to play contradictory roles in SARS-CoV-2 infection. Methods A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally. Results We revealed that the HLA-DR + CD38 + CD8 + T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR + CD38 dim and HLA-DR + CD38 hi . We observed a persistent accumulation of HLA-DR + CD38hi CD8 + T cells in severe COVID-19 patients. These HLA-DR + CD38 hi CD8 + T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR + CD38 dim CD8 + T cells. Moreover, the clinical and laboratory data supported that only HLA-DR + CD38 hi CD8 + T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Conclusions Our findings indicated that HLA-DR + CD38 hi CD8 + T cells were correlated with disease severity of COVID-19 rather than HLA-DR + CD38 dim population.
【저자키워드】 COVID-19, severity, HLA-DR, CD38, immune disorder, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, Cytokines, severe COVID-19, Hospitalization, T cells, Influenza, SARS-COV-2 infection, disease severity, chemokines, public health crisis, CD8, Health crisis, lymphopenia, Growth factors, Retrospective study, sensitivity, T cell, Multiplex assay, outbreak, Patient, severe cases, Mild, Ebola, Hospital admission, systemic inflammation, Severe patient, expression, Care, moderate, HLA-DR, CD38, COVID-19 patients, critical cases, tissue injury, dysregulation, Factor, immune disorders, severe patients, Serum level, Blood samples, serum levels, laboratory data, Beijing, transcriptional regulation, influenza infection, blood sample, severe COVID-19 patients, overactivation, heterogeneous, Clinical and laboratory data, inhibitory, disease severity of COVID-19, killing, apoptotic, flow cytometric, Result, collected, examined, caused, died, recruited, reported, indicated, evaluated, supported, correlated, Progressive, subset, manifested, stimulatory, infected with SARS-CoV-2, 【제목키워드】 CD8, persistent, immune disorder, percentage,