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).
ABSTRACT
Background: Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19. Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses. To our knowledge, no case-control study of COVID-19 in OTR has been published to-date. Methods: We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020. After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls). All patients were discharged from the hospital or died. Results: 16 KTR had COVID-19. All 3 KTR off IS, who were excluded from further analyses, survived. Median age was 54 (range: 34-65) years;5/13 KTR (38.4%) were men. Median time from transplant was 41 (range: 1-203) months. Two KTR, both transplanted >10 years ago, were managed as outpatients. IS was reduced in 12/13 (92.3%), most often by discontinuation of the antimetabolite. IL6 levels were >1,000 (normal: < 5) pg/mL in 3 KTR. Tacrolimus or sirolimus levels were >10 ng/mL in 6/9 KTR (67%) (Table 1). Eleven KTR were hospitalized (84.6%) and matched with 44 controls. One KTR, the only one treated with hydroxychloroquine, died (CFR 5.8%;7.6% in KTR on IS;9% in hospitalized KTR on IS). Four controls died (CFR: 9%;state CFR: 5.2%;inpatient CFR: 16.6%). There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls. Four KTR (30.7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab. KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2). Conclusion: Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients. Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction. Extremely high IL6 levels were common. The role of IS and potential benefits from investigational treatments remain to be elucidated. A larger multi-institutional study is underway. (Table Presented).