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与新冠病毒肺炎患者严重急性呼吸综合征冠状病毒2病毒RNA脱落、抗体反应及死亡率相关的自然杀伤细胞

Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients.

作者信息

Bao Changqian, Tao Xiandong, Cui Wei, Hao Yuanyuan, Zheng Shuaike, Yi Bin, Pan Tiewen, Young Ken H, Qian Wenbin

机构信息

Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.

The Third Affiliated Hospital of Naval Medical University, 200438, Shanghai, China.

出版信息

Exp Hematol Oncol. 2021 Jan 27;10(1):5. doi: 10.1186/s40164-021-00199-1.

Abstract

Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two consecutively negative SARS-CoV-2 viral RNA test ( interval ≥ 24 hours), improved respiratory symptoms and obvious absorption of inflammation in pulmonary imaging are the discharge criteria for COVID-19 patients. The clearance profile of viral RNA in the upper respiratory tract specimens, including nasopharyngeal swab and/or oropharyngeal swabs, is related to innate immune cells such as Natural Killer cells. A total of 168 patients were included for the study. In this cohort, non-severe and severe groups showed significant differences in white blood cells, neutrophils, lymphocytes, basophils and platelets counts, as well as in infection related parameters such as CRP and serum cytokine IL-6. For lymphocyte subsets tests at admission, the severe group displayed significantly lower cell counts than the non-severe group. Higher counts of total T cells, CD4 + T cells, CD8 + T cells, and NK cells in peripheral blood showed a significant correlation with the shorter time taken to obtain the first negative viral RNA test and first positive IgM/ IgG antibody test. The number of B cells was only correlated with time to achieve the first positive IgM/IgG test. The count of NK cells was also correlated with a higher level of IgG antibody (p = 0.025). The lymphocytopenia group had a significantly worse survival rate (p = 0.022) and a longer duration (p = 0.023) of viral shedding than the normal lymphocyte count group. A lower NK cell count correlates the most with the worse survival rate (p<0.001) and a longer duration (p<0.001) of viral shedding. This study suggests the potential value of allo-Natural Killer cell therapy as an universal COVID-19 treatment strategy.

摘要

2019冠状病毒病(COVID-19)是一种由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的新型传染性病毒性疾病。连续两次严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒RNA检测结果均为阴性(间隔≥24小时)、呼吸道症状改善以及肺部影像学炎症明显吸收是COVID-19患者的出院标准。包括鼻咽拭子和/或口咽拭子在内的上呼吸道标本中病毒RNA的清除情况与自然杀伤细胞等固有免疫细胞有关。共有168例患者纳入本研究。在该队列中,非重症组和重症组在白细胞、中性粒细胞、淋巴细胞、嗜碱性粒细胞和血小板计数以及感染相关参数如CRP和血清细胞因子IL-6方面存在显著差异。入院时淋巴细胞亚群检测显示,重症组细胞计数显著低于非重症组。外周血中总T细胞、CD4 + T细胞、CD8 + T细胞和自然杀伤细胞数量较高与首次病毒RNA检测呈阴性和首次IgM/IgG抗体检测呈阳性所需时间较短显著相关。B细胞数量仅与首次IgM/IgG检测呈阳性的时间相关。自然杀伤细胞计数也与较高水平的IgG抗体相关(p = 0.025)。淋巴细胞减少组的生存率显著更差(p = 0.022),病毒脱落持续时间更长(p = 0.023),高于淋巴细胞计数正常组。自然杀伤细胞计数越低与生存率越差(p<0.001)和病毒脱落持续时间越长(p<0.001)的相关性最大。本研究提示了同种异体自然杀伤细胞疗法作为一种通用的COVID-19治疗策略的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c57d/7842039/9630fe90cffc/40164_2021_199_Fig1_HTML.jpg

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