Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM⁺ or IgG1⁺ and continued to rise until 150 days. RBD-specific IgG⁺ Bmem were predominantly CD27⁺, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

SARS-CoV-2感染后的持久免疫力受到质疑，因为血清抗体的恢复能力下降。但是，功能性免疫是由长寿的记忆T和B（Bmem）细胞介导的。因此，我们生成了荧光标记的穗受体结合结构域（RBD）和核衣壳蛋白（NCP）的四聚体，以确定COVID-19患者中SARS-CoV-2特异性Bmem细胞的寿命和免疫表型。在症状发作后4天至242天之间，从25名COVID-19患者中获得了36份血液样本，其中包括11份配对样本。尽管在所有患者中均发现了针对RBD和NCP的血清IgG，但症状发作后20天抗体水平开始下降。RBD和NCP特异性Bmem细胞主要表达IgM ⁺或IgG1 ⁺并持续上升直至150天。RBD特异性IgG ⁺ Bmem主要为CD27 ⁺，其数目与循环性滤泡辅助性T细胞数目显着相关。因此，SARS-CoV-2抗体应答随着RBD和NCP特异性Bmem细胞的持久性恢复而收缩。SARS-CoV-2特异性Bmem细胞的流式细胞术检测能够检测感染或接种COVID-19后的长期免疫记忆。