Immune damage mechanisms of COVID-19 and novel strategies in prevention and control of epidemic.
Immune damage mechanisms of COVID-19 and novel strategies in prevention and control of epidemic.
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DOI：
10.3389/fimmu.2023.1130398
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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2019冠状病毒病（COVID-19）由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起，临床表现多样，是该病的主要特征，而其根本原因是人群中不同机体的免疫反应不同。SARS-CoV-2及其变异株对危重病的损伤机制与其他危重病相同，如炎症反应过度、I型干扰素的双刃作用、补体系统过度激活等。针对COVID-19的特异性免疫损伤机制，我们首次提出急性病毒感染诱导的T细胞应答导致老年患者"急性T细胞衰竭"，不仅是T细胞数量减少、功能障碍的外周衰竭，也是中枢免疫器官失去对外周免疫器官的免疫稳态的中枢衰竭，而增加胸腺输出量可在药物治疗的帮助下减轻病情，降低死亡率。我们发现，SARS-CoV-2引起的免疫反应也可以攻击次级淋巴器官，如脾脏，淋巴结和肾脏，以及我们通常认识的肺。结合对免疫保护机制的认识，我们研制了冠状病毒抗原诊断试剂盒和治疗性单克隆抗体。未来，我们将进一步研究冠状病毒感染引起的免疫损伤和保护机制，为开发新的疫苗和免疫疗法提供更科学的策略。
Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has diverse clinical manifestations, which is the main feature of the disease, and the fundamental reason is the different immune responses in different bodies among the population. The damage mechanisms of critical illness by SARS-CoV-2 and its variants, such as hyperinflammatory response, a double-edged function of type I interferon, and hyperactivation of the complement system, are the same as other critical illnesses. Targeting specific immune damage mechanisms of COVID-19, we scored the first to put forward that the responses of T cells induced by acute virus infection result in “acute T-cell exhaustion” in elderly patients, which is not only the peripheral exhaustion with quantity reduction and dysfunction of T cells but also the central exhaustion that central immune organs lost immune homeostasis over peripheral immune organs, whereas the increased thymic output could alleviate the severity and reduce the mortality of the disease with the help of medication. We discovered that immune responses raised by SARS-CoV-2 could also attack secondary lymphoid organs, such as the spleen, lymphoid nodes, and kidneys, in addition to the lung, which we generally recognize. Integrated with the knowledge of mechanisms of immune protection, we developed a coronavirus antigen diagnostic kit and therapeutic monoclonal antibody. In the future, we will further investigate the mechanisms of immune damage and protection raised by coronavirus infection to provide more scientific strategies for developing new vaccines and immunotherapies.