Clinical insights into the role of immunosuppression and its disturbances in solid organ transplant recipients with coronavirus disease 2019.

Background The ongoing COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation. Objectives To analyze a cohort of transplant recipients in our practice who developed COVID-19, with a focus on immunosuppressive regimen, tacrolimus blood levels, clinical course, and patient and graft outcomes. Methods During the first 12 months of the pandemic, we identified patients diagnosed with SARS-CoV-2 infection among our ambulatory cohort, including kidney, liver, and heart transplant recipients. Baseline and follow-up data concerning graft function, immunosuppression details, and patient and graft outcomes were analyzed. Results Of 2091 ambulatory patients, 201 (9.6%) with diagnosed SARS-CoV-2 infection were identified, including 112 kidney, 56 heart, and 33 liver transplant recipients. COVID-19 cases were significantly more common among those who had recently undergone kidney (during 2015-2020) or heart transplantation (during 2020) than earlier recipients. Additionally, blood levels of tacrolimus measured during or shortly after COVID-19 in 23 kidney graft recipients were significantly increased (median increase, 76.1%; interquartile range: 47.4%-109.4%) relative to pre-dose trough levels, but liver function values were not concomitantly elevated, necessitating a tacrolimus dose reduction in 73.9% of these patients. Conclusions In our cohort of transplant recipients, we found substantial disturbances of tacrolimus metabolism in kidney recipients, which may play a role in the worsening of kidney function during SARS-CoV-2 infection. In addition, we found that infections were more common with recent kidney or heart transplantation, and results suggest the potential importance of immunosuppressive regimen strength for SARS-CoV-2 infection-related morbidity.