Table_1_The Quality of Anti-SARS-CoV-2 T Cell Responses Predicts the Neutralizing Antibody Titer in Convalescent Plasma Donors.DOCX

Convalescent plasma therapy has been described as an attractive approach to treat critically ill patients with COVID-19 (Coronavirus disease 2019). The selection of convalescent plasma donors (CPD) is commonly based on neutralizing antibody titer. A better understanding of the quality of immune responses following COVID-19 will enable the optimization of convalescent donors' selection in convalescent plasma programs. The involvement of SARS-CoV-2 specific T cells in the induction and persistence of high affinity anti-SARS-CoV-2 neutralizing antibody is still poorly investigated. In this study, 115 CPD who presented SARS-CoV-2 and who were eligible for plasma donation were included. Comprehensive analysis of T cells together with humoral responses were performed in regards of sex, age and blood group type. High frequency of T cell responses against SARS-CoV-2 related protein such as spike glycoprotein (80.0%), nucleocapsid (NCAP) (70.4%) and membrane protein (VME1) (74.8%) were detected in CPD by ex vivo IFN-γ and TNF-α ELISpot assays. Among CPD responders, most exhibited poly-specific T cell responses (75%) defined by the ability to mount responses against at least two SARS-CoV-2 antigens. We found a positive correlation between the magnitude and the poly-specificity of anti-SARS-CoV-2 T cell responses in CPD. Notably, both the magnitude and poly-specificity of SARS-CoV-2 T cell responses were highly correlated with neutralizing antibody titer in CPD. The present study highlights that the poly-specificity and strength of SARS-CoV-2 specific T cell responses predicts neutralizing antibody titer following COVID-19. These observations show the interest to combine T cell assays and antibody titer for the selection of CPD and to a latter extend to assess COVID-19 vaccine efficacy in at-risk patients.

恢复期血浆疗法已被证实是治疗新型冠状病毒肺炎（Coronavirus disease 2019，COVID-19）重症患者的极具潜力的治疗策略。恢复期血浆捐献者（convalescent plasma donors, CPD）的遴选通常以中和抗体滴度为核心依据。更深入地了解新型冠状病毒肺炎感染后免疫应答的质量，将有助于优化恢复期血浆捐献项目中的捐献者遴选流程。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）特异性T细胞在高亲和力抗SARS-CoV-2中和抗体的诱导与维持过程中所发挥的作用，目前仍未得到充分研究。本研究纳入了115名曾感染SARS-CoV-2且符合血浆捐献资质的恢复期血浆捐献者。研究人员针对性别、年龄与血型类型，对T细胞应答与体液免疫应答进行了综合分析。通过体外干扰素-γ（IFN-γ）与肿瘤坏死因子-α（TNF-α）酶联免疫斑点试验（ELISpot），在恢复期血浆捐献者中检测到针对SARS-CoV-2相关蛋白的高频率T细胞应答，其中针对刺突糖蛋白、核衣壳蛋白（nucleocapsid, NCAP）与膜蛋白（membrane protein, VME1）的应答阳性率分别为80.0%、70.4%与74.8%。在产生T细胞应答的捐献者中，多数呈现出多特异性T细胞应答（占比75%），即能够针对至少两种SARS-CoV-2抗原产生免疫应答。本研究发现，在恢复期血浆捐献者中，抗SARS-CoV-2 T细胞应答的强度与其多特异性呈正相关。值得注意的是，在恢复期血浆捐献者中，SARS-CoV-2特异性T细胞应答的强度与多特异性均与中和抗体滴度呈显著正相关。本研究证实，SARS-CoV-2特异性T细胞应答的多特异性与强度可用于预测新型冠状病毒肺炎感染后的中和抗体滴度水平。上述研究结果表明，将T细胞检测与抗体滴度检测相结合用于恢复期血浆捐献者的遴选具有重要应用价值，后续还可将该方案拓展用于评估高危人群的COVID-19疫苗保护效力。