Elevated tacrolimus levels in hospitalized organ transplant recipients with COVID-19

ABSTRACT

Purpose: The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied. Methods: We retrospectively studied hospitalized adult (>18-year-old) OTRs with COVID-19, who were receiving tacrolimus and were hospitalized between 3/1 and 12/16/2020. Categorical data were compared by Fisher's exact test, and continuous by the Mann-Whitney and Wilcoxon rank sum tests for unrelated or paired samples, respectively. Results: We studied 30 OTRs. 67% were men, 90% had a kidney transplant. Two were heart transplant and one small intestine transplant recipients. Median age was 60.5 (range 21-84) years, median time from transplant 36 (range 1-224) months. Tacrolimus troughs were significantly higher on admission for COVID-19 than baseline (average trough in the 6 months prior) median 11.5 vs. 7.4 ng/mL, P=0.001;Fig. 1. Patients with diarrhea had higher tacrolimus trough levels, compared to those without diarrhea (P=0.09). We found no significant association between tacrolimus trough and acute kidney injury or bacterial infections. Compared to OTRs with tacrolimus trough <10 ng/mL, those with trough >10 ng/mL were more likely to have elevated aspartate aminotransferase (AST) on admission (P=0.01, Fig. 2) and require supplemental oxygen during hospital admission (P=0.026, Fig. 1 black lines represent OTR requiring supplemental oxygen). Conclusions: Tacrolimus trough levels were substantially elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed;management of immunosuppression should be individualized. (Table Presented).