Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19
Juan Du, Lirong Wei, Guoli Li, Mingxi Hua, Yao Sun, Di Wang, Kai Han, Yonghong Yan, Chuan Song, Rui Song, Henghui Zhang, Junyan Han, Jingyuan Liu, Yaxian Kong
Abstract
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.