Distinct B cell repertoires characterize patients with mild and severe COVID-19 [GEX]. Distinct B cell repertoires characterize patients with mild and severe COVID-19 [GEX]

Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2 binding plasma cells and memory B cells after infection or vaccination. Previous work has shown evidence that germinal center reactions, a critical component of the B cell response, are disrupted in severe COVID-19. This may adversely affect protective immunity from re-infection. Consistent with an extrafollicular B cell response, severe COVID-19 patients have large scale changes in B cell populations such as elevated frequencies of clonally expanded, class switched, unmutated plasmablasts. However, it is not clear whether mild or asymptomatically infected individuals show similar differences in B cell repertoires. Here, we use single cell RNA sequencing of B cells to show that, in contrast to hospitalized COVID-19 patients, mildly symptomatic COVID-19 subjects have B cell repertoires skewed towards clonally diverse, somatically hypermutated memory B cells approximately 30 days after the onset of symptoms. This provides evidence that B cell responses are less disrupted in mild COVID-19, and that the infection resolves with the production of memory B cells. Overall design: Characterization of B cell response in mild symptomatic COVID-19 patients

针对新型冠状病毒肺炎（COVID-19）的保护性免疫，大概率依赖于感染或接种疫苗后，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）结合浆细胞与记忆B细胞（memory B cells）的生成。既往研究已证实，作为B细胞应答（B cell response）关键组成部分的生发中心反应（germinal center reactions），在重型COVID-19患者体内受到破坏。这可能会对再次感染后的保护性免疫产生不利影响。与滤泡外B细胞应答（extrafollicular B cell response）相符的是，重型COVID-19患者的B细胞群体发生了大规模改变，例如克隆扩增、类别转换（class switched）、未突变的浆母细胞（plasmablasts）频率升高。然而，目前尚不清楚轻症或无症状感染者的B细胞库（B cell repertoires）是否存在类似差异。本研究通过对B细胞进行单细胞RNA测序（single cell RNA sequencing）发现，与住院的COVID-19患者相比，轻症有症状COVID-19受试者在症状出现约30天后，其B细胞库偏向于克隆多样性高、体细胞超突变（somatically hypermutated）的记忆B细胞。这表明轻症COVID-19患者的B细胞应答受到的破坏更小，且感染可通过产生记忆B细胞而痊愈。实验整体设计：轻症有症状COVID-19患者的B细胞应答特征分析。