Yang Jingyi, Zhong Maohua, Hong Ke, Yang Qingyu, Zhang Ejuan, 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 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 (CAS) Wuhan China.
Clin Transl Immunology. 2021 Mar 4;10(3):e1259. doi: 10.1002/cti2.1259. eCollection 2021.
SARS-CoV-2 has caused a worldwide pandemic of COVID-19. The existence of prolonged SARS-CoV-2 positivity (PP) has further increased the burden on the health system. Since T cells are vital for viral control, we aimed to evaluate the characteristics of T-cell responses associated with PP.
We established a PP cohort and two age- and sex-matched control cohorts: a regular clinical recovery (CR) cohort and a healthy donor (HD) cohort. The mean time for RNA negativity conversion in the PP cohort was markedly longer than that in the CR cohort (66.2 vs 25.3 days), while the time from illness onset to sampling was not significantly different. T-cell responses in the PP cohort were assayed, analysed and compared with those in the CR and HD cohorts by flow cytometry and ELISpot analysis of peripheral blood mononuclear cells.
Compared with the CR cohort, the proliferation, activation and functional potential of CD8 and CD4 T cells in the PP cohort were not significantly different. However, the frequencies and counts of Teff and Tem in CD8 but not in CD4 T cells of the PP cohort were prominently lower. Moreover, a weaker SARS-CoV-2 N protein-specific IFN-γ T-cell response and a higher frequency of Tregs were detected in the PP cohort.
Suppressed CD8 T-cell differentiation is associated with PP and may be an indicator for the prediction of prolonged SARS-CoV-2 positivity in COVID-19 patients. The association between suppressed CD8 T-cell differentiation and elevated Tregs warrants studies in the future.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已引发了全球范围内的2019冠状病毒病（COVID-19）大流行。SARS-CoV-2长期阳性（PP）的存在进一步加重了卫生系统的负担。由于T细胞对病毒控制至关重要，我们旨在评估与PP相关的T细胞反应特征。
我们建立了一个PP队列以及两个年龄和性别匹配的对照队列：一个常规临床康复（CR）队列和一个健康供体（HD）队列。PP队列中RNA转阴的平均时间明显长于CR队列（66.2天对25.3天），而从发病到采样的时间无显著差异。通过对外周血单个核细胞进行流式细胞术和酶联免疫斑点分析，对PP队列中的T细胞反应进行检测、分析并与CR和HD队列进行比较。
与CR队列相比，PP队列中CD8和CD4 T细胞的增殖、活化及功能潜力无显著差异。然而，PP队列中CD8而非CD4 T细胞的效应性T细胞（Teff）和记忆性T细胞（Tem）的频率和数量显著更低。此外，在PP队列中检测到较弱的SARS-CoV-2 N蛋白特异性干扰素-γ T细胞反应以及更高频率的调节性T细胞（Tregs）。
CD8 T细胞分化受抑制与PP相关，可能是预测COVID-19患者SARS-CoV-2长期阳性的一个指标。CD8 T细胞分化受抑制与Tregs升高之间的关联值得未来进一步研究。
