COVID-19 Hospitalization in Solid Organ Transplant Recipients on Immunosuppressive Therapy

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.

Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service

“…Solid organ transplant (SOT) recipients had more than a two-fold increase in risk for severe COVID-19 outcomes, which supports the observations made in previous studies [ 38 – 40 ]. It revealed that the higher the type and dose of immunosuppressants, the more susceptible the transplanted organ, such as the heart or lungs, the higher the risk of serious illness if the patient is older or has an underlying disease [ 39 , 40 ]. Those patients have to be put on immunosuppressants to suppress rejection in transplanted organs and reduce their defense against virus or bacterial infections [ 41 ].…”

Comparison of COVID-19 Hospitalization and Death Between Solid Organ Transplant Recipients and the General Population in Canada, 2020–2022

“…Older age is an established major risk factor for serious COVID-19 illness but our findings highlight that recipients experience serious outcomes at a younger age, likely because of the presence of several other risk factors (eg, comorbidities like diabetes and the use of immunosuppression medications). 26,27 Across the 7 COVID-19 pandemic waves, we found the lowest incidence rate of severe COVID-19 in solid organ transplant recipients occurred in the last 2 waves (ie, waves 6 and 7), which encompassed the Omicron era. However, we found the risk of severe COVID-19 remained substantially higher than the general population across all waves.…”

“…[15][16][17]24 One potential reason for the higher risk of severe outcomes is because of the need for higher immunosuppression in these groups, with 1 study finding mycophenolic acid and steroids are associated with in an increased COVID-19 hospitalization risk. 25,26 This highlights that multiorgan and lung transplant recipients are particularly vulnerable populations that might require enhanced protections and perhaps novel therapies to target SARS-CoV-2 infections. In accordance with ICES privacy policies, cell sizes ≤5 cannot be reported; this includes being able to calculate small cells based on other information provided.…”

“…Older age is an established major risk factor for serious COVID-19 illness but our findings highlight that recipients experience serious outcomes at a younger age, likely because of the presence of several other risk factors (eg, comorbidities like diabetes and the use of immunosuppression medications). 26 , 27…”

Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality

“…Our data also suggest that the hospitalization rates of LT recipients were not affected by the COVID-19 pandemic. Recently, a cohort study of 14464 LT recipients demonstrated that the use of tacrolimus may also decrease the risk of COVID-19 hospitalization compared to steroids and mycophenolic acid[ 38 ]. In our LT cohorts, it is possible that a number of patients were on tacrolimus, potentially decreasing the need for hospitalization.…”