The Effect Of COVID-19 Infection On Tacrolimus Metabolism In Heart Transplant

INTRODUCTION: There is limited knowledge regarding the effects of COVID-19 in heart transplant recipients. Reliance on tacrolimus levels has become a cornerstone of management strategy to balance the immune response with the potential for rejection of the graft. How COVID-19 and its treatment affect tacrolimus metabolism in solid organ transplant is not well understood. Here we present a case of a heart transplant recipient with highly elevated tacrolimus levels following COVID-19 infection despite little to no tacrolimus administration and no other known drug-drug interactions. CASE PRESENTATION: The patient is a 58-year-old male with history of ischemic cardiomyopathy; status post orthotopic heart transplantation 6/17/2018. The postoperative course was complicated by two occurrences of 2R cellular rejection within 1 year, RV dysfunction, calcineurin induced renal dysfunction, and relative bradycardia. In 7/2020, the patient presented to the ED with complaints of jaw pain, symptoms of urinary retention and 3 days of diarrhea. COVID-19 PCR returned positive. Before infection, the patient had been maintained on a steady dose of tacrolimus 0.5mg BID for 8 months with associated trough levels between the goal range of 4-8ng/mL. At the time of infection, the patient's tacrolimus was held to account for elevated trough levels, and he was then maintained on a dose of 0.5mg QAD for the next 8 months. DISCUSSION: Tacrolimus metabolism is represented in Graph 1 via trough:dose (T:D) ratio (T:D ratio measured in 48-hr intervals as the patient was on QAD dosing post-infection). T:D ratio remained stable on tacrolimus 0.5mg BID before COVID-19 infection. Following infection, the ratio sharply rose and remained elevated 8 months later despite reducing the dose to 0.5mg QAD. To our knowledge, this is the first case presented of a heart transplant recipient with altered tacrolimus metabolism status post COVID-19 infection without apparent drug-drug interaction. This suggests a relationship between SARS-COV-2 viremia with tacrolimus metabolism.