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Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients
Jordi Colmenero1, Manuel Rodríguez-Perálvarez2, Magdalena Salcedo3
1Liver Transplant Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Insights
Liver transplant patients face a higher risk of COVID-19 but have lower mortality rates. Mycophenolate may increase severe COVID-19 risk, suggesting dose adjustment could be beneficial.
Area of Science:
- Immunology
- Transplant Surgery
- Infectious Diseases
Background:
- Outcomes of COVID-19 in immunocompromised populations, including liver transplant recipients, remain under investigation.
- Assessing COVID-19 incidence and severity in liver transplant patients is crucial for clinical management.
Purpose of the Study:
- To evaluate the incidence and outcomes of coronavirus disease 2019 (COVID-19) in a cohort of liver transplant patients.
- To identify predictors of severe COVID-19 in this immunocompromised group.
Main Methods:
- A prospective, nationwide study of liver transplant patients with COVID-19 during the Spanish outbreak (February-April 2020).
- Calculation of standardized incidence and mortality ratios (SIR and SMR) compared to the general population.
- Multivariate Cox regression analysis to identify independent predictors of severe COVID-19.
Main Results:
- 111 liver transplant patients diagnosed with COVID-19; incidence was 191.2 per 100,000 population.
- 86.5% hospitalized, 19.8% required respiratory support, 10.8% admitted to ICU.
- Mortality rate was 18%, lower than the matched general population (SMR=95.5).
- Mycophenolate-based immunosuppression was an independent predictor of severe COVID-19 (RR=3.94), especially at higher doses.
Conclusions:
- Liver transplant patients have an increased risk of contracting COVID-19 but experience lower mortality compared to the general population.
- Mycophenolate dose reduction or withdrawal may prevent severe COVID-19 in hospitalized patients.
- Complete immunosuppression withdrawal is not recommended; temporary conversion to other agents may be beneficial.
Background & Aims:
The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate.
Methods:
We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression.
Results:
A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit.
Conclusions:
Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged.
Lay Summary:
In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.
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