Early life B cell responses and inflammation following SARS-CoV-2 infection

摘要 截至2021年3月，SARS-CoV-2已造成超过5000万人感染，200万人死亡。 这是现代世界前所未有的大流行病。虽然感染者 在感染后迅速产生针对病毒刺突的IgG应答，一些研究已经 表明轻度感染的个体产生较弱的中和抗体反应 与那些患有严重疾病的人相比。自然免疫后免疫反应的持久性 感染及其对后续感染和新出现的相关变体的保护 仍然不清楚。有趣的是，与其他呼吸道病毒不同， SARS CoV-2感染后。住院儿童的抗体应答和 发展为多系统炎症综合征（MIS-C）的患者的特征已经得到了描述，但是， 在抗体的数量、质量、持久性和广度方面的知识存在差距， 无症状或轻度症状儿童的反应，可能导致 使儿童与成人相比不易受到严重感染。而且 在先前感染的儿童中再感染或感染新变异的可能性不是 为没有童年的儿童重新建立集体环境提供了可能性， 疫苗很有挑战性。我们的首要目标是表征动力学，功能， SARS-CoV-2感染引起的体液免疫应答的广度和持久性 与成人相比，儿科年龄谱。我们假设儿科 对SARS-CoV-2感染的免疫应答与成人不同， 预防有症状的疾病和持久的免疫力。使用来自两个 目前正在进行的关于成人和儿童SARS-CoV-2感染的独特社区研究， 我们的假设通过以下目的：1）定义的相似性和差异， SARS-CoV-2特异性抗体应答的动力学、幅度、特异性、功能和持久性， 儿童和成人; 2）调查SARS中抗体反应的广度和效力- CoV-2感染的儿童对抗SARS-CoV-2的已确定和预测变体;以及3） 定义SARS-CoV-2特异性B细胞库并表征儿科疫苗的效力 SARS CoV-2特异性单克隆抗体。这些评估将确定免疫相关性 预防严重疾病，并为免疫战略提供见解， SARS CoV-2可能成为地方性病原体，需要长期控制。

Abstract As of March 2021, SARS-CoV-2 has caused more than 50 million infections and 2 million deaths, constituting an unprecedented pandemic in the modern world. While infected individuals rapidly develop IgG responses against the viral Spike after infection, some studies have indicated that individuals with mild infection generate weaker neutralizing Ab responses compared to those with severe disease. The durability of the immune response following natural infection and its afforded protection against subsequent infections and emerging related variants remain unclear. Interestingly, unlike other respiratory viruses, children are rarely develop severe disease following SARS CoV-2 infection. Antibody responses in hospitalized children and those who developed the multisystem inflammatory syndrome (MIS-C) have been characterized, but, there is a gap in knowledge of the magnitude, quality, durability, and breadth of antibody responses in asymptomatic or mildly symptomatic children, responses that may contribute to making children less susceptible to severe infection compared to adults. Moreover, the possibiltiy of reinfection or infection with a novel variant in previously-infected children is not known, making the possibility of restarting congregate settings for children without a childhood vaccine quite challenging. Our overarching goal is to characterize the kinetics, function, breadth, and durability of humoral immune responses elicited by SARS-CoV-2 infection across the pediatric age spectrum in comparison to that of adults. We hypothesize that pediatric immune responses to SARS-CoV-2 infection is distinct from that of adults, and associates with protection against symptomatic disease and durability of immunity. Using samples from two unique ongoing community studies of SARS-CoV-2 infections in adults and children, we will test our hypothesis through the following aims: 1) Define the similarities and differences in the kinetics, magnitude, specificity, function and durability of SARS-CoV-2-specific Ab responses in children and adults; 2) Investigate the breadth and potency of antibody responses in SARS- CoV-2-infected children against established and predicted variants of SARS-CoV-2; and 3) Define the SARS-CoV-2-specific B cell repertoire and characterize the potency of pediatric SARS CoV-2-specific monoclonal antibodies. These evaluations will identify immune correlates of protection against severe disease and provide insights for immunization strategies towards the long term control of SARS CoV-2 which will likely become an endemic pathogen.