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5000多万人感染，200万人 死亡，构成了现代世界前所未有的大流行。虽然受感染的人 一些研究表明，感染后迅速产生针对病毒尖峰的免疫球蛋白G反应 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异的保护作用 目前仍不清楚。有趣的是，与其他呼吸道病毒不同的是，儿童很少出现严重的 SARS CoV-2感染后的疾病。住院儿童和非住院儿童的抗体反应 谁发展了多系统炎症综合征(MIS-C)的特征已经被描述，但是， 人们对抗体的大小、质量、持久性和广度的认识存在差距。 无症状或轻度症状儿童的反应，这些反应可能有助于 使儿童比成年人更不容易受到严重感染。此外， 以前感染过病毒的儿童再感染或感染新变种的可能性不大 已知，这使得为没有童年的儿童重新开始集会设置成为可能 疫苗是相当具有挑战性的。我们的首要目标是描述动力学、功能、 SARS-CoV-2感染引起的体液免疫反应的广度和持久性 儿童年龄谱与成人年龄谱的比较。我们假设儿科医生 对SARS-CoV-2感染的免疫反应与成人不同，并与 对症状性疾病的保护和免疫的持久性。使用的样本来自两个 正在进行的关于成人和儿童感染SARS-CoV-2的独特社区研究，我们将测试 我们的假设通过以下目的来实现：1)定义两种模式的异同 SARS-CoV-2特异性抗体应答的动力学、大小、特异性、功能和持久性 儿童和成人；2)调查SARS抗体反应的广度和效力- 冠状病毒-2感染儿童对SARS-CoV-2确诊和预测变种的抵抗力；以及3) 确定SARS-CoV-2特异性B细胞谱系并表征儿童SARS-CoV-2的效力 SARS CoV-2特异性单抗。这些评估将确定免疫相关因素 对严重疾病的预防，并为以下免疫战略提供见解 SARS CoV-2的长期控制可能成为地方性病原体。

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.