Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients

ABSTRACT

Purpose: Kidney transplant recipients (KTR) are at increased risk of mortality from COVID-19. We conducted a cohort study among KTR from the French Solid Organ Transplant COVID-19 (SOT COVID) registry to investigate the association between maintenance immunosuppressive drugs and 60-day mortality in KTR with COVID-19. Method(s) Data from all KTR with COVID-19 included in SOT COVID 02/28/2020 and 12/30/2020 were retrieved. Among them, 116 were excluded because of missing data on immunosuppressive therapy. We evaluated associations between immunosuppressive drugs and death <=60 days of 1st symptoms using logistic regression, with all baseline characteristics considered to influence outcome or immunosuppressive regimen. Benjamini-Hochberg correction was used for controlling false positive rate;40 multiple imputations were performed. Adjusted p-value <0.05 was considered statistically significant. Result(s) There were 1,451 KTR included. Median age was 58 years, 963 (66.4%) were men. Most frequent comorbidities were hypertension (n=1188, 81.9%), diabetes (501, 34.5%), cardiovascular disease (428, 29.5%). Median time since transplant was 71 months. Maintenance immunosuppression regimen included calcineurin inhibitors (1295, 89.2%), antimetabolites (1205, 83%), corticosteroids (1094, 75.4%), Mammalian Target of Rapamycin inhibitors (144, 9.9%) and belatacept (58, 4.0%). Among 1,451 KTR, 201 (13.9%) died <=60 days. Older age and baseline creatininemia were associated with mortality (OR 1.09 [1.07-1.11];1.01 [1.005- 1.009], p<0.001). Corticosteroid-free regimens were associated with a significantly lower risk of death (OR 0.48 [0.31;0.76], p=0.011). All other variables yielded non-significant adjusted p-values. Conclusion(s) Corticosteroid-free regimens were associated with a lower risk of death in KTR with COVID-19. While a short course of high-dose corticosteroids is beneficial in severely ill COVID-19 patients, prolonged maintenance corticosteroids expose to chronic immune disorders that may predispose KTR to severe forms of COVID-19.