COVID-19诱发的免疫损伤机制研究支撑疫情防控

The Immune Damage Caused by SARS-CoV-2 Infection

SARS冠状病毒2型(Severe Acute Respiratory Syndrome Coronavirus 2,SARS-CoV-2)感染导致新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19),主要特征是同一病毒感染导致迥然不同的临床后果,而同一病毒在不同机体诱导不同的免疫反应是其根本原因。SARS-CoV-2及其变异株感染导致重症、危重症具有与其他重症感染共性损伤机制,如高炎症反应、I型干扰素两相反应及补体系统过度活化等。针对COVID-19的特殊免疫损伤机制,我们在国际上率先发现急性病毒感染诱导的T细胞应答可导致老年人“急性T细胞功能耗竭”,该耗竭状态不但是外周耗竭,表现为T细胞减少和功能降低,还表现为中枢耗竭即中枢免疫器官对外周自稳的机制缺失,而通过药物增加胸腺输出可减轻疾病严重度及减少死亡;发现SARS-CoV-2感染引起的免疫反应还可攻击二级淋巴器官如脾脏和淋巴结及肺以外的靶器官—肾脏;结合保护性免疫机制的认识,我们研发了新冠病毒抗原诊断试剂盒及治疗性单克隆抗体等。后期将围绕冠状病毒感染的免疫损伤和免疫保护机制进行深入研究,为新型疫苗和免疫治疗技术的发展提供科学依据。

The coronavirus disease 2019(COVID-19)severe patients who were suffered from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection manifested with inflammatory storm,delayed secretion of type I interferon and over-activation of complement system.SARS-CoV-2 induces the dysregulation of innate immune responses,which further reshapes the adaptive immune system,leading to“lymphopenia”,and finally causes delay of virus clearance.Our group has focused on the immune injury mechanism caused by of SARS-CoV-2,we firstly reported that the virus infection can promote“acute T cell function depletion”in the world.Most important,we found that Thymosin-αinjection can reverse T cell exhaustion,by thus improves the progress of disease.Moreover,we also found that SARS-CoV-2 directly invades the kidney and secondary lymphoid organs including spleen and lymph nodes.Based on these results,we are developing coronavirus universal vaccine,a diagnostic kit of based on SARS-CoV-2 N antigen etc.In the future,we would cooperate with other groups in China to carry out the immune evaluation of coronavirus vaccines.