T cell repertoire profiling in allografts and native tissues in recipients with COVID-19 after solid organ transplantation: insight into T cell-mediated allograft protection from viral infection

The effects of the SARS-CoV-2 virus on the body remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of severe disease manifestations and graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for treating these vulnerable patients. Existing knowledge about the effects of the SARS-CoV-2 virus on transplanted organs is limited to histological findings. There are no known studies of viral levels in graft versus native tissue or T cell responses throughout the native and graft tissues. We addressed this knowledge gap by investigating transplant recipients at our institution who died from SARS-CoV-2 and underwent autopsy or whose grafts were biopsied during active SARS-CoV-2 infection. Severe disease correlated with elevated inflammatory markers, but we identified no difference in viral load or distribution of COVID-specific T cells between allograft and native tissue. Our findings suggest a previously uncharacterized systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and is consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly. Notably, these findings likely apply to non-transplant patient as well.

目前人们对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对人体的影响仍未完全阐明。其中一类受重点关注的特殊人群为移植受者，因其本身处于免疫抑制状态。阐明新型冠状病毒肺炎（COVID-19）综合征移植患者中重症临床表现与移植物功能障碍的病理生理学机制，对这类易感患者的临床救治具有重要指导价值。目前关于SARS-CoV-2对移植器官影响的既有认知仅局限于组织学发现，尚无针对移植物与自体组织间病毒载量差异，或贯穿自体与移植物组织的T细胞应答的相关研究。本研究针对本机构内死于SARS-CoV-2感染且接受尸检，或在活动性SARS-CoV-2感染期间接受移植物活检的移植受者开展分析，填补了这一研究空白。研究发现，重症疾病与炎症标志物升高存在相关性，但未在同种异体移植物与自体组织间观察到病毒载量或新冠特异性T细胞分布的显著差异。本研究结果提示，实体器官移植患者针对SARS-CoV-2存在一种此前未被表征的全身免疫应答，该应答与排斥反应无关，且与受者人类白细胞抗原（HLA）限制性T细胞克隆的广泛破坏性作用高度一致——这类克隆对供体器官与自体器官的影响并无差异。值得注意的是，上述研究结论或同样适用于非移植患者。