Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models^1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

迄今为止，严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 已感染 7800 万人，并导致超过 170 万人死亡。感染与具有中和活性的不同水平抗体的发展有关，这可以在动物模型中防止感染^1,2. 抗体水平随着时间的推移而降低，但是，据我们所知，尚未检查再感染时产生抗体所需的记忆 B 细胞的性质和质量。在这里，我们报告了一组 87 人在感染 SARS-CoV-2 后 1.3 个月和 6.2 个月时的体液记忆反应。我们发现，在此期间，针对 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 的 IgM 和 IgG 抗体的滴度显着下降，而 IgA 受到的影响较小。同时，在假型病毒检测中，血浆中和活性降低了五倍。相比之下，RBD 特异性记忆 B 细胞的数量在感染后 6.2 个月时保持不变。记忆 B 细胞在 6.2 个月后显示克隆更新，它们表达的抗体具有更大的体细胞超突变，对 RBD 突变的抵抗力和增加的效力，表明体液反应的持续进化。对 2019 年冠状病毒病 (COVID-19) 发病后 4 个月无症状个体的肠道活组织检查进行的免疫荧光和 PCR 分析显示，SARS-CoV-2 核酸在 14 人中有 7 人的小肠中持续存在和免疫反应性。我们得出结论，记忆 B 细胞对 SARS-CoV-2 的反应在感染后 1.3 到 6.2 个月之间以与抗原持久性一致的方式演变。对 2019 年冠状病毒病 (COVID-19) 发病后 4 个月无症状个体的肠道活组织检查进行的免疫荧光和 PCR 分析显示，SARS-CoV-2 核酸在 14 人中有 7 人的小肠中持续存在和免疫反应性。我们得出结论，记忆 B 细胞对 SARS-CoV-2 的反应在感染后 1.3 到 6.2 个月之间以与抗原持久性一致的方式演变。对 2019 年冠状病毒病 (COVID-19) 发病后 4 个月无症状个体的肠道活组织检查进行的免疫荧光和 PCR 分析显示，SARS-CoV-2 核酸在 14 人中有 7 人的小肠中持续存在和免疫反应性。我们得出结论，记忆 B 细胞对 SARS-CoV-2 的反应在感染后 1.3 到 6.2 个月之间以与抗原持久性一致的方式演变。