The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity.
The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity.
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DOI：
10.1038/s41392-021-00525-3
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发表时间：
2021-03-08
影响因子：
39.3
通讯作者：
Ye L
中科院分区：
文献类型：
--
作者：
Gao L;Zhou J;Yang S;Wang L;Chen X;Yang Y;Li R;Pan Z;Zhao J;Li Z;Huang Q;Tang J;Hu L;Liu P;Zhang G;Chen Y;Ye L
保护患者免受由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）的适应性免疫尚未得到很好的表征。特别是，已发现无症状患者可诱导微弱且短暂的SARS-CoV-2抗体反应，但其潜在机制仍不清楚;与此同时，指导这些无症状患者康复的保护性免疫力尚不清楚。在这里，我们在10名无症状患者和64名其他疾病严重程度的患者中描述了SARS-CoV-2特异性B细胞和T细胞反应的特征（轻度，n = 10，中度，n = 32，重度，n = 12），并发现无症状或轻度症状的患者未能产生病毒特异性生发中心（GC）B细胞应答，其导致稳健和延长的体液免疫，通过GC反应指示剂评估，包括滤泡辅助T（TFH）细胞和记忆B细胞反应以及血清CXCL 13水平。或者，这些患者产生了有效的病毒特异性TH 1和CD 8 + T细胞应答。与此形成鲜明对比的是，中度或重度疾病的患者诱导了强烈的病毒特异性GC B细胞应答和相关的TFH应答;然而，在这些患者中，病毒特异性TH 1和CD 8 + T细胞的诱导程度最低。因此，这些结果揭示了无症状患者的保护性免疫，也揭示了不同疾病严重程度的COVID-19患者的体液和细胞免疫反应具有惊人的二分法和不完全性，为合理设计有效的COVID-19疫苗提供了重要见解。
The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.
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