Affiliation:
1. EPI-PHARE, Scientific Interest Group in Epidemiology of Health Products, French National Agency for the Safety of Medicines and Health Products, French National Health Insurance, Saint-Denis, France
2. Anti-Infective Evasion and Pharmacoepidemiology Team, INSERM UMR1018, School of Medicine Simone Veil, University Versailles Saint-Quentin-en-Yvelines, Paris-Saclay University, Montigny-Le-Bretonneux, France
3. Department of Nephrology-Dialysis-Transplantation, Bicêtre University Hospital, Assistance Publique–Hôpitaux de Paris, Paris-Saclay University, Le Kremlin-Bicêtre, France
4. Assistance Publique–Hôpitaux de Paris, Hepato-Biliary Centre, Paul Brousse Hospital, Unit INSERM 1193, Villejuif, France
5. Departement of Lung Transplantation and Mucoviscidose Reference Centre, Foch Hospital, Suresnes, France
6. Clinical Research Unit, Université Paris-Saclay, Direction of Clinical Research, Assistance Publique–Hôpitaux de Paris, Paris, France
Abstract
ImportanceSolid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19–related severity in this population are still insufficiently explored in the literature.ObjectiveTo examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19–related hospitalization in solid organ transplant recipients.Design, Setting, and ParticipantsUsing the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022.ExposuresImmunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities).Main Outcomes and MeasuresThe main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately.ResultsOverall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients.Conclusions and RelevanceThis study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19–related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.
Publisher
American Medical Association (AMA)