The Effect Of Covid-19 Infection On Sirolimus Metabolism In Heart Transplant

INTRODUCTION: Limited knowledge exists regarding the effect of Covid-19 on heart transplant recipients. Monitoring immunosuppressant levels is an important management strategy concerning the risk of graft rejection. Furthermore, how Covid-19 and its treatment affect sirolimus metabolism in solid organ transplants is not well understood. Here, we present a case of a heart transplant recipient with elevated sirolimus levels following Covid-19 infection. The elevated sirolimus levels occurred after previously being therapeutic on a steady dose and persisted despite significant dose reductions and no other known drug-drug interactions. CASE PRESENTATION: The patient is a 58-year-old male with a history of ischemic cardiomyopathy; status post orthotopic heart transplantation on 8/17/2009. The postoperative course was complicated by atrial tachycardia without rejection status post-ablation in 8/2020 and end-stage renal disease on hemodialysis. In January of 2022, the patient was instructed to present to the ER after missing dialysis due to Covid-like symptoms including generalized weakness, nausea, and shortness of breath. Covid-19 PCR returned positive. Before infection, the patient had been maintained on a steady dose of sirolimus 0.5 mg daily for 5 months with associated trough levels between the goal range of 4-8 ng/mL. At the time of infection, the patient's sirolimus was held due to elevated trough levels, and he was subsequently maintained on a dose of 0.5 mg every other day for the next few days. Seeing no improvement, the dose was then decreased to 0.25 mg every other day for the remainder of his admission. He expired on 2/09/2022 from Covid-19. Figure 1 shows the sirolimus trough:dose ratio before and after diagnosis of Covid-19. DISCUSSION: To our knowledge, this is the first case presented of a heart transplant recipient with altered sirolimus metabolism status post Covid-19 infection without apparent drug-drug interactions. This may suggest a relationship between SARS-COV-2 viremia with sirolimus metabolism.