Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients
Authors: Jordi Colmenero, Manuel Rodríguez-Perálvarez, Magdalena Salcedo, Ana Arias-Milla, Alejandro Muñoz-Serrano, Javier Graus, Javier Nuño, Mikel Gastaca, Javier Bustamante-Schneider, Alba Cachero, Laura Lladó, Aránzazu Caballero, Ainhoa Fernández-Yunquera, Carmelo Loinaz, Inmaculada Fernández, Constantino Fondevila, Miquel Navasa, Mercedes Iñarrairaegui, Lluis Castells, Sonia Pascual, Pablo Ramírez, Carmen Vinaixa, María Luisa González-Dieguez, Rocío González-Grande, Loreto Hierro, Flor Nogueras, Alejandra Otero, José María Álamo, Gerardo Blanco-Fernández, Emilio Fábrega, Fernando García-Pajares, José Luis Montero, Santiago Tomé, Gloria De la Rosa, José Antonio Pons
Journal: Journal of Hepatology (2020)

•The incidence of coronavirus disease 2019 (COVID-19) is higher in liver transplant patients.•Mortality rates are lower than those observed in the matched general population.•Immunosuppression withdrawal may not be justified.•Mycophenolate may increase the risk of severe COVID-19 in a dose-dependent manner.•Calcineurin inhibitors and everolimus are not deleterious for COVID-19. Background & AimsThe incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate.MethodsWe 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.ResultsA 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.ConclusionsBeing 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 summaryIn 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. The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. 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. 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. 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.