(133) Immunosuppressive therapy and covid-19-related hospitalization in solid organ transplant recipients: a French nationwide cohort study

Publication Number: 470

Background: Solid organ transplant recipients (SOTR) population is considered at high risk of severe infection compared with the general population. However, factors of covid-19-related severity in this population are insufficiently explored in the literature.

Objectives: To identify immunosuppressive drugs against graft rejection and health conditions associated with the risk of severe covid-19 in SOTR population.

Methods: Using the French national health data system, we identified SOTR between date of birth and the entry into the cohort on 15 February 2020, and we included those of them who received at least one reimbursement for an immunosuppressive drug, i.e. tacrolimus, cyclosporine, azathioprine, mycophenolic acid, sirolimus and everolimus, in the six months before the date of entry. The outcome was the occurrence of a severe sars-cov-2 infection defined by hospitalization for covid-19 reported between 15 February 2020 and 31 July 2022. The maintenance immunosuppressive drugs and other factors associated with the outcome were identified with a non-conditional logistic regression. Confounding by indication was controlled for using a multivariate model with adjustment for individual confounders.

Results: Of the 60456 SOTR included in the study, 41463, 14464, 5327, and 2823 were kidney, liver, heart, and lung transplanted, respectively. Among them, 12.5%, 6.4%, 12.9%, and 18.0% of renal, liver, heart, and lung transplant recipients experienced a severe infection, respectively. In kidney transplant recipients, steroids (aOR=1.60 [1.49-1.73]) and mycophenolic acid (aOR=1.37 [1.25-1.51]) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (aOR=0.77 [0.61-0.98]) is associated with a decreased risk and, steroids (aOR=1.60 [1.38-1.86]), mycophenolic acid (aOR=1.61 [1.37-1.90]) increased the risk of hospitalizations. In heart transplant recipients, ciclosporin (aOR=0.67 [0.47-0.94]) is associated with a decreased risk and, steroids (aOR=1.42 [1.11-1.82]), mycophenolic acid (aOR=1.29 [1.02-1.64]), sirolimus (aOR=2.71 [1.20-6.09]), everolimus (aOR=1.24 [1.01-1.51]) are associated with an increased risk of hospitalization. Only steroids (aOR=1.72 [1.19-2.48]) are associated with a high risk of Covid-19 hospitalization in lung transplant recipients. Compared with patients on a triple drugs regimen, those on a single, double drugs regimens were associated with a decreased risk of severe infection in each organ transplant subgroup.

Conclusions: Mycophenolic acid, sirolimus/everolimus and long corticosteroid therapy in SOTR increase the risk of severe covid-19 due to their cytotoxic effects. These findings should be considered for the management of SOTR with sars-cov-2 infection.