key: cord-0721560-01g5wozt
authors: Tejedor-Tejada, Javier; Fuentes-Valenzuela, Esteban; Alonso-Martin, Carmen; Almohalla-Alvarez, Carolina; Garcia-Pajares, Felix
title: COVID-19 and short and medium-term outcomes in liver transplant patients: A spanish single-center case series
date: 2021-05-31
journal: J Clin Exp Hepatol
DOI: 10.1016/j.jceh.2021.05.009
sha: 2b8ffa39fba8a1fc7809813da48c63c4231d69a4
doc_id: 721560
cord_uid: 01g5wozt

BACKGROUND & AIMS: The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium and short-term outcomes in liver transplant patients. PATIENTS AND METHODS: A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021, were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications and liver graft function were assessed at diagnosis and 3-month follow-up. RESULTS: Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalised (50%) and 8 (50%) hospitalised patients were analyzed. The median follow-up was 5.33 months (IQR 3.06-8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnoea and fatigue were the most prevalent symptoms during the 3-months follow-up. No Liver graft dysfunction were reported despite of partial immunosuppression withdrawal in 4 patients (25%). One patient had cardiovascular complications. CONCLUSIONS: Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3-month after COVID-19. However, no cases of loss or liver graft dysfunction were reported.

The evidence suggests that most vulnerable subjects to COVID-19 infection suffer from patients with comorbidities or immunosuppression, including liver transplant recipients. Liver graft dysfunction may be a rare complication. Some patients complain about the post-COVID-19 syndrome. The aim of this study was to assess medium and short-term outcomes in liver transplant patients.

A retrospective case series was performed at a tertiary referral center. We screened 845 patients who had liver transplant (LT) in our center. All consecutive LT patients with COVID-19 during the Spanish outbreak from March 2020 to April 2021, were included. Demographics, pre-existing comorbidities, clinical and radiological data of COVID-19 infection, complications and liver graft function were assessed at diagnosis and 3-month follow-up.

Overall, 20 LT patients were diagnosed with confirmed COVID-19. We included 16 patients that met the inclusion criteria, 8 nonhospitalised (50%) and 8 (50%) hospitalised patients were analyzed. The median follow-up was 5.33 months (IQR 3.06-8.26). One patient died during the follow-up. All patients presented some grade of respiratory or functional symptoms. Dyspnoea and fatigue were the most prevalent symptoms during the 3-months follow-up. No Liver graft dysfunction were reported despite of partial immunosuppression withdrawal in 4 patients (25%). One patient had cardiovascular complications.

Our results suggest the presence of post-COVID-19 syndrome with mild residual physical and psychological dysfunction in this subgroup of patients at 3-month after COVID-19. However, no cases of loss or liver graft dysfunction were reported. The severe respiratory distress syndrome coronavirus (SARS-CoV-2) is responsible for COVID-19 disease. The liver involvement has been described in various studies 1 , with some potential role of cholangiocytes due to their high expression of virus receptor angiotensin-converting enzyme 2 (ACE2) (2) . Liver damage could be induced by cytopathic effect of the virus, cytokine storm or drug toxicity 2 .

The pandemic has affected liver transplantation (LT) units worldwide reducing their activity 3 . Although, data about the risk of LT patients for contracting the virus are limited and the role of immunosuppression in the inflammatory response remain Recently, the Spanish experience regarding LT recipients and COVID-19 infection was published, suggesting an increased risk of acquiring the infection without higher mortality rates 4 . An international register found that LT was not independently associated with lower survival. However, worse outcomes following COVID-19 were related to comorbidities 5 .

Some studies have suggested that COVID-19 patients can experience some symptoms after being discharged called "post-COVID-19 syndrome" 6 . This syndrome could affect physical and mental health with the need for rehabilitation. Then, even though the short-term outcomes seem to be like the general population, the medium and longterm outcomes or the possible effect on the graft has not been described yet.

Thus, the aim of this study was to assess short and medium-term outcomes in LT patients with COVID-19.

Design and study population J o u r n a l P r e -p r o o f This was a single center retrospective study including all adult ( 18 years) LT recipients routinely followed at Hospital Universitario Rio Hortega (Valladolid, Spain) and diagnosed with COVID-19 from March 2020 to April 2021. We screened 845 LT patients at our center. Patients whose follow-up was less than 1 month after the COVID-19 diagnosis were excluded. The study protocol was approved by the local Ethic 

Descriptive statistics were used to report characteristics of patients. Normally distributed values were shown as mean ± standard deviation (SD), otherwise as median and interquartile range whenever appropriate. Student t or nonparametric test were used to compare continuous variable and X 2 test or Fisher´s exact test was used for categorical variables, wherever appropriate. Statistical analyses were performed using IBM SPSS Statistic for Windows, (Version 24.0. IBM Corp, NY, USA). P-values <0.05 was considered statistical significance.

From March 2020 to April 2021, a total of 20 LT patients (2 Re-LT patients) were diagnosed with COVID-19. Two patients died due to acute respiratory distress syndrome during hospitalization and 2 hospitalized patients had not been discharged at the time of writing this manuscript and were therefore excluded for the present analysis. 

During the follow-up, one patient with comorbidities died 39 days after COVID-19 hospitalization discharge due to cardiac insufficiency secondary to acute coronary syndrome and cardiac dysfunction as COVID-19 cardiovascular complication.

Many uncertainties remain about the impact of COVID-19 infection in LT population, including the recovery and short and medium-term outcomes. We present a case series to report the partial physical and psychological recovery after COVID-19 infection in LT patients in a Spanish region with a high COVID-19 incidence.

The incidence of COVID-19 among LT recipients in our center was 2.37% (20/845). All patients were followed up using COVID-19 screening tests, telephone interviews or conventional clinic visits. COVID-19 cases were registered in local database.

Despite the heterogeneity of time interval from LT (4-190 months) and age (ranging from 54 to 74 years), the short and medium-term outcomes of COVID-19 infection were associated with comorbidities and respiratory failure. Also, hospitalized patients were older and had more comorbidities than non-hospitalized patients.

The rate of hospitalization, pneumonia and ICU admission were similar to other published series of solid organ transplant recipients 13 .

As recent published data 14 There are some limitations that should be mentioned, as a retrospective study. Despite screening the database thoroughly, we cannot exclude some degree of underreporting. Secondly, our study was conducted at a single LT centre with a small sample size. Future larger studies are needed to validate our results and determine long-term outcomes.

In conclusion, our analysis reveals that all LT patients had a partial recovery with residual medical problems at 3-month. Moreover, this report highlights the need of physical and psychological follow-up and monitoring the liver allograft function after COVID-19 in LT patients. 

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