key: cord-0755658-j4klwm07
authors: Salerno, David M.; Kovac, Danielle; Corbo, Heather; Jennings, Douglas L.; Lee, Jennifer; Choe, Jason; Scheffert, Jenna; Hedvat, Jessica; Chen, Justin; Tsapepas, Demetra; Rosenblatt, Russell; Samstein, Benjamin; Halazun, Karim; Verna, Elizabeth; Pereira, Marcus; Brennan, Corey; Husain, Syed A.; Mohan, Sumit; Brown, Robert S.
title: SARS‐CoV‐2 infection increases tacrolimus concentrations in solid‐organ transplant recipients
date: 2021-01-05
journal: Clin Transplant
DOI: 10.1111/ctr.14193
sha: a893701420103da325fe1ce1c87687e9dde4aa26
doc_id: 755658
cord_uid: j4klwm07

Calcineurin inhibitors (CNI) are narrow therapeutic index medications, with drug concentrations altered by factors such as drug-drug interactions, clinical symptoms including diarrhea, and hepatic dysfunction. Supratherapeutic CNI concentrations can produce a myriad of toxicities, the most worrisome of which are renal injury and seizures.

No funding provided support for this research. In this IRB-approved, multicenter retrospective study, we identified all solid-organ transplant recipients with a SARS-CoV-2 PCRpositive nasopharyngeal swab from March 15 to April 9, 2020. The primary outcome was the difference in dose-corrected trough concentration at baseline and upon presentation for COVID-19 infection. Twenty-one patients (20.6%) presented with a trough concentration >15 ng/ml. Mortality was higher in those patients presenting with a trough above 15 ng/ml 6/21 (28.6%) vs. 8/81 (9.9%) in those below; p = .027. There was no difference in values for AST, ALT, or bilirubin in the patients presenting with a trough value above or below 15 ng/ml. No patients presented with overt seizure activity, while 52 (51%) presented with AKI.

We are the first to report an increase in tacrolimus serum concentrations in solid-organ transplant recipients with COVID-19 infection. While the mechanism of this association may be unclear, COVID-19 infection has been associated with many physiologic alterations including cytokine storm, 2 venous thromboembolism, 3 AKI, 4 neurologic abnormalities, 5 and multisystem inflammatory syndrome (MIS-C) in children 6 without a yet identified mechanism. The phenotypic plasticity of COVID-19 infection in organ transplant recipients has been described as a higher incidence of diarrhea and higher disease severity upon presentation. 1 However, diarrhea is unlikely to explain the increased exposure in our cohort because trough concentrations were higher in patients without diarrhea as a presenting symptom. There are a few hypotheses that may explain the association be- 

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How to cite this article

SARS-CoV-2 infection increases tacrolimus concentrations in solid-organ transplant recipients