Influence of immunosuppressant management on mortality in kidney transplant recipients hospitalized with covid-19

ABSTRACT

Purpose: Kidney transplant recipients are thought to be at high risk for mortality from COVID-19 due to the necessity for chronic immunosuppressive therapy to prevent graft rejection. However, the optimal immunosuppressant management strategy for patients with COVID-19 remains unknown. Methods: We conducted a single-center, retrospective review of all kidney or kidneypancreas transplant recipients with a functioning graft who were hospitalized with COVID-19 between 3/15/2020-5/15/2020. Patients were followed from the date of admission, up until 1 month following hospital discharge or study conclusion (6/15/2020). Multivariable logistic regression was used to identify potential patient or immunosuppression characteristics associated with the development of severe COVID-19 and in-hospital mortality. Results: 69 (3.2%) patients followed longitudinally at our center were hospitalized with COVID-19 during the review period, 38 of whom were admitted to the study institution. Patients were ethnically diverse, and the majority were receiving tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) at baseline. Following COVID-19 diagnosis, median tacrolimus trough levels decreased by-11% (-26%-+17%) during hospitalization and mycophenolate doses were reduced by at least 50% in 33 patients. Adjunctive therapy included hydroxychloroquine (68.4%), convalescent plasma (26.3%), anticoagulation (52.6%), and participation in clinical trials (10.5%). Twenty patients developed severe disease, and 11 (28.9%) died during hospitalization. Admission characteristics associated with increased risk for mortality included age (OR=2.0;1.0-4.0) and history of HIV (OR=22.6;1.1-483.7). No association was found between baseline tacrolimus trough levels, mycophenolate dosing, or the number of immunosuppressants prescribed and COVID-19 mortality. Similarly, the degree of immunosuppression reduction following hospital admission was not associated with survival or severe disease progression. No differences were observed in the prescription of adjunctive therapies, with the exception of a higher daily dose of prednisone equivalents in patients who died (37.0 vs 15.4;p=0.02). Among survivors, death-censored allograft survival was 96.2% at 1-month, and no cases of biopsy proven rejection were observed during the review period. Conclusions: The findings from our study confirm age as a significant risk factor for COVID-19 mortality in kidney transplant recipients, and suggest HIV status as an additional risk factor that may warrant further investigation. Pre-emptive immunosuppression reduction does not appear to be warranted, as baseline immunosuppression intensity and dose modulation following diagnosis of infection were not associated with hospital outcomes. However, no episodes of acute rejection were observed, so providers may wish to consider immunosuppression reduction on a case-by-case basis.