Treg cells
Treg cells are indispensable for the maintenance of immune self-tolerance and homeostasis through inhibiting effector cells quantitatively and qualitatively [48]. The excessive inflammation is the hallmark of severe COVID-19 [49, 50]. The proportion of Treg cells was significantly lower in hospitalized COVID-19 patients compared to non-hospitalized patients, suggesting a potential defect in the generation of immunosuppressive cells [35]. Indeed, some hospitalized COVID-19 patients with an impaired Treg response mounted a stronger CD4-CTL responses [35]. In addition, Tregs in severe COVID-19 patients present a striking Treg phenotype, with highFoxP3 expression [51], an increased proportion, activation status and up-regulated effector molecules (ENTPD1, HPGD, IL12RB2 ) [51-53] (Figure 1). And a significant increase in the frequency of CXCR3 expressing Tregs with increasing severity was observed, suggesting migration of Tregs to lungs [52] (Figure 1). Similarly, the frequency of Treg cells was approximately 3-fold higher in pulmonary fibrosis index (FI) high patients compared with FI low patients [52]. Importantly, the recently identified SARS-CoV-2 docking receptor basigin (BSG or CD147) and FURIN showed elevated expression in Tregs of aged patients with COVID-19, which may contribute to the increased susceptibility of aged patients to COVID-19 [54]. Taken together, Tregs cells played a detrimental role in preventing excessive inflammation. Treg-based immunotherapy which has been applied in autoimmune and inflammatory diseases [55], may provide feasible regimens for treating COVID-19.
CD8 + T cells
CD8+ T cells were markedly reduced but CD8+/CD4+ T cell ratio was higher in COVID-19-infected patients [25, 56-58], which was also evidenced by clonally-expanded CD8+ T cells in the blood and bronchoalveolar lavage using scRNA-seq analysis [42, 59, 60]. CD8+ T cells highly expressed activation markers, such as CD69, TNFAIP3 and HLA class II genes (HLA-DRA ,HLA-DRB1 , and HLA-DRB5 ) [30, 34] (Figure 1). The heightened state of T cell activation may hinder development of T cell responses directed specifically against SARS-CoV-2 infection [61]. In addition, activated CD8+ T cells enriched in severe COVID-19 patients expressed high levels of chemokines such as CXCR3 and CCR6, which might promote the migration of activated CD16+ T cells into the inflamed lungs and promote microvascular endothelial cell injury [52]. The quantitative and qualitative of CD8+ T-cell population undergo changes in COVID-19 patients. Understanding the composition of CD8+ T cells and the associations with different clinical manifestations of COVID-19 patients will help to develop rational therapeutic approaches.