Yang Jingyi, Zhong Maohua, Zhang Ejuan, Hong Ke, Yang Qingyu, Zhou Dihan, Xia Jianbo, Chen Yao-Qing, Sun Mingbo, Zhao Bali, Xiang Jie, Liu Ying, Han Yang, Xu Mengxin, Zhou Xi, Huang Chaolin, Shang You, Yan Huimin
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology & Wuhan Jinyintan Hospital, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430023, China.
J Mol Cell Biol. 2021 Jul 6;13(3):197-209. doi: 10.1093/jmcb/mjab014.
Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.
尽管数百万患者已从新冠病毒感染中临床康复，但对于这些个体中淋巴细胞的免疫状态却知之甚少。在本研究中，对临床康复（CR）队列的外周血单个核细胞与年龄和性别匹配的健康供体队列的外周血单个核细胞进行了比较分析。我们发现，CR队列中的CD8⁺T细胞具有更多数量的效应T细胞和效应记忆T细胞，但Tc1（IFN-γ⁺）、Tc2（IL-4⁺）和Tc17（IL-17A⁺）细胞频率较低。CR队列中的CD4⁺T细胞频率降低，尤其是中央记忆T细胞亚群。此外，CR队列中的CD4⁺T细胞程序性细胞死亡蛋白1（PD-1）表达较低，Th1（IFN-γ⁺）、Th2（IL-4⁺）、Th17（IL-17A⁺）和循环滤泡辅助性T细胞（CXCR5⁺PD-1⁺）频率也较低。因此，尽管激活标志物CD71水平升高，但CR队列中B细胞中的同种型转换记忆B细胞（IgM-CD20hi）比例显著降低。对于CR队列中的CD3-HLA-DR⁻淋巴细胞，除了IFN-γ、颗粒酶B和T-bet水平较低外，未观察到T-bet与IFN-γ之间的相关性。此外，考虑到出院后的天数，所有与功能降低相关的表型在4至11周内均未显示出恢复的趋势。CR队列中淋巴细胞的显著表型改变表明，严重急性呼吸综合征冠状病毒2感染对淋巴细胞有深远影响，甚至在临床康复后也可能导致功能障碍。
