[HTML][HTML] Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients

HY Zheng, M Zhang, CX Yang, N Zhang… - Cellular & molecular …, 2020 - nature.com
HY Zheng, M Zhang, CX Yang, N Zhang, XC Wang, XP Yang, XQ Dong, YT Zheng
Cellular & molecular immunology, 2020nature.com
The novel contagious primary atypical pneumonia epidemic, which broke out in Wuhan,
China, in December 2019, is now formally called Coronavirus Disease 2019 (COVID-19),
with the causative virus named as Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2). 1, 2 Recent studies have shown that in addition to dyspnea, hypoxemia, and
acute respiratory distress, lymphopenia, and cytokine release syndrome are also important
clinical features in patients with severe SARS-CoV-2 infection. 3 This suggests that …
The novel contagious primary atypical pneumonia epidemic, which broke out in Wuhan, China, in December 2019, is now formally called Coronavirus Disease 2019 (COVID-19), with the causative virus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). 1, 2 Recent studies have shown that in addition to dyspnea, hypoxemia, and acute respiratory distress, lymphopenia, and cytokine release syndrome are also important clinical features in patients with severe SARS-CoV-2 infection. 3 This suggests that homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. To provide direct evidence on leukocyte homeostasis, we studied the immunological characteristics of peripheral blood leukocytes from 16 patients admitted to the Yunnan Provincial Hospital of Infectious Diseases, Kunming, China. Among them, 10 were mild cases, 6 were severe cases; 7 were≥ 50 years old, 11 were younger; and 6 had baseline diabetes, hypertension, or coronary atherosclerosis (Supplementary Table S1). Similar to the healthy group (n= 6), the absolute numbers of cells of major leukocyte subsets in peripheral blood remained at a normal level in both mild and severe patients. Different from that reported by Chen et al., 4 we did not observe increased neutrophils or decreased lymphocytes. Instead, we found that the severe group had a significant reduction in granulocytes compared to the mild group (Fig. 1 a). It has been reported that elevated inflammatory mediators play a crucial role in fatal pneumonia caused by pathogenic human coronaviruses such as SARS and MERS (Middle East respiratory syndrome). 5 We therefore examined whether inflammatory mediators can impact progression in COVID-19 patients. However, no statistical differences in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) plasma concentrations were found among the three groups. Although patients had higher sCD14 levels than healthy people, there were no significant differences between the severe and mild groups (Fig. 1 b). Virus-induced inflammatory factor storms can cause a systemic T cell response, reflected as changes in the differentiation and activity of T cells. 6 Here, as significant differences in virus-induced inflammatory cytokines were not detected, we next examined whether homeostasis was perturbed in T cells at the cellular level (Supplementary Table S2, Supplementary Fig. S1). As shown in Fig. 1 c, the proportions of multiple molecules related to T cell activation and regulation increased significantly in patients compared to healthy controls, but several functional molecules showed a marked decrease. Among the differentially expressed functional molecules, the levels of interferon-γ (IFN-γ) and TNF-α in CD4+ T cells were lower in the severe group than in the mild group, whereas the levels of granzyme B and perforin in CD8+ T cells were higher in the severe group than in the mild group. The activation molecules showed no differences in CD4+ T cells, whereas the levels of HLA-DR and TIGIT in CD8+ T cells were higher in the severe group than in the mild group (Fig. 1 c). These data indicate that COVID-19, similar to some chronic infections, damages the function of CD4+ T cells and promotes excessive activation and possibly subsequent exhaustion of CD8+ T cells. Together, these perturbations of T cell subsets may eventually diminish host antiviral immunity. 7 Usually a single molecule does not adequately predict disease progression. We therefore further performed cluster analysis on marker expression using data obtained from flow cytometry. Our results showed significant differences among the …
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