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.