Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases, 100039, Beijing, China.
Department of Clinical Medicine, Bengbu Medical College, 233000, Bengbu, China.
Nat Commun. 2020 Jul 8;11(1):3410. doi: 10.1038/s41467-020-17240-2.
COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
COVID-19 的死亡率为 5.1%。虽然 COVID-19 患者的病毒学、流行病学、临床和管理结果特征已迅速确定，但炎症和免疫特征仍需要确定，因为它们会影响 COVID-19 的发病机制和临床表达。在这里，我们发现与轻症患者相比，重症患者的淋巴细胞减少、CD4+T 细胞、CD8+T 细胞和 NK 细胞选择性丧失、T 细胞过度激活和 T 细胞抑制分子高表达更为明显。重症患者的 CD8+T 细胞表达高水平的细胞毒性分子。对一名死亡患者的肺组织进行组织化学研究显示，SARS-CoV-2 RNA 的亚解剖分布以及大量 T 细胞和巨噬细胞浸润。因此，严重 COVID-19 患者中发生了异常激活和失调的 CD8+T 细胞，这可能是 SARS-CoV-2 感染的发病机制，并表明针对免疫的治疗干预靶点可能是治疗严重 COVID-19 患者的有希望的方法。
