PDF(Pubmed)
Abstract：
The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.
摘要：
免疫保护成分控制COVID-19疾病的严重程度，以及长期适应性免疫维持和随后的再次感染风险在初始COVID-19严重程度上的差异，仍未澄清。这里,我们纵向分析了165例按严重程度分类的COVID-19患者在急性感染和恢复期的SARS-CoV-2特异性免疫效应因子.我们发现早期和强大的SARS-CoV-2特异性CD4+和CD8+T细胞反应可以改善疾病进展并缩短住院时间。而延迟和减毒的病毒特异性CD8+T细胞反应是COVID-19突出的严重特征。延迟的抗病毒抗体产生而不是滴度水平与严重的结果相关。相反，最初的COVID-19严重程度标志着SARS-CoV-2特异性适应性免疫的长期维持，证明与轻度/中度恢复期相比,重度恢复期患者表现出更持续的病毒特异性抗体和记忆T细胞应答.此外，最初的COVID-19严重程度与SARS-CoV-2再感染风险呈负相关。总的来说,我们的研究揭示了病毒特异性T细胞反应的时间特征与COVID-19严重程度之间复杂的相互作用,以指导未来的SARS-CoV-2波管理.
