key: cord-281086-fmftr5jn
authors: Morand, A.; Roquelaure, B.; Colson, P.; Amrane, S.; Bosdure, E.; Raoult, D.; Lagier, J-C; Fabre, A
title: Child with liver transplant recovers from COVID-19 infection. A case report
date: 2020-05-06
journal: Arch Pediatr
DOI: 10.1016/j.arcped.2020.05.004
sha: 
doc_id: 281086
cord_uid: fmftr5jn

Abstract We present the case of a 55-month-old girl who recovered from coronavirus disease 2019 (COVID-19) infection 5 months after undergoing liver transplantation; she had a co-infection with Epstein–Barr virus (EBV). To the best of our knowledge, this is the first case report of a COVID-19 infection in a pediatric patient with liver transplantation. Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.

J o u r n a l P r e -p r o o f 3 We herein present the case of a 55-month-old girl who was infected with coronavirus disease 2019 (COVID-19) 5 months after undergoing liver transplantation. After an uneventful birth at term, she was diagnosed with congenital cholestasis due to biliary atresia and underwent Kasai portoenterostomy (KPE) at 53 days of age. KPE was partially successful, but in the following years she developed portal hypertension with refractory ascites and angiocholitis.

Liver transplantation (from her father) was performed without major complications at the age of 50 months. The patient was discharged 20 days after the procedure on tacrolimus immunosuppression therapy and with no immunization against Epstein-Barr virus (EBV) before the transplantation. She had mildly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (approx. 1. A few days before the child's presentation, the mother, a 29-year-old woman with no medical history, presented with rhinopharyngitis. She felt progressively tired and had a fever, cough, polypnea, thoracic pain, and headache. She was referred to the Méditerranée Infection University Hospital Institute where she was diagnosed with COVID-19 by RT-PCR of a nasopharyngeal swab [1] . She was hospitalized in the Contagious Infections Diseases Department. Low-dose computed tomography showed bilateral, asymmetrical, peripheral frosted-glass images and two alveolar condensation foci in two different segments of the right lung. This was compatible with COVID-19 pneumonia. The mother was treated with oral hydroxychloroquine and oral azithromycin [2] . On the fourth day of treatment, the results of her nasopharyngeal samples were negative and within 8 days she was discharged from hospital and followed up as an outpatient.

The young liver transplant girl had rhinitis starting from mid-March, 2020, shortly after the onset of her mother's symptoms. Two days later, she suffered from fever, cough, and polypnea, and 3 days later she was referred to the Méditerranée Infection University Hospital Institute at the same time as her mother, where she was also diagnosed with COVID-19 after a nasopharyngeal swab test. To the best of our knowledge, this is the first case report of a liver transplantation patient with COVID-19. Although children seem to have a less severe reaction to COVID-19 than J o u r n a l P r e -p r o o f 5 adults [3] , even when they have significant health complications [4] , there have been some doubts regarding immunosuppression therapy and the risk of severe infections as they are usually negatively correlated. An immunocompromised state has been associated with increased risk of severe lower respiratory tract disease in patients with coronavirus [5] . Contrary to other viruses, during the COVID-19 infection, the host's innate immune response seems to be the main cause of lung tissue damage [6] . It should be noted that the most important factors in adult patients are age, sex, and a history of hypertension [7] . A report of the successful recovery of 52-year-old renal transplantation patient was recently published [8] .

Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. Two studies reported patients having a positive serology result for EBV at the same time as a COVID-19 infection, but EBV DNA was not assessed [9, 10] . A single study conducted in China aimed to assess the role of EBV co-infection during COVID-19. In all, 35 out of 62 COVID-19 patients (56.5%) were seropositive for EBV viral capsid antigen (VCA) IgM antibody, which reflects an acute EBV infection or reactivation [10] . EBV was reported to be correlated with a more severe course of COVID-19. The authors noted that EBV-positive COVID-19 patients had a 3.64-fold higher risk of presenting with fever (95% CI: 1.26-10.5;

p=0.02), higher CRP levels (p=0.01), and a lower proportion of CD8+ and CD4/CD8 lymphocytes (p=0.048 and =0.046, respectively) than EBV-negative patients. The median recovery time for EBV-seropositive COVID-19 patients was higher than for EBV-negative patients, without being statistically significant (p=0.07) [10] . These authors hypothesized that EBV infection and COVID-19 share some pathogenic characteristics such as an overactivation of T cells, which can lead to severe immune injury [11] . In fact, even if EBV infection is often asymptomatic [12] , some people present with fever, asthenia, myalgia, sore throat, anorexia, skin rash, and the disease can be fatal, especially in immunocompromised individuals [13] . Therefore, the clinical case of our young immunocompromised patient recovering from EBV infection at the same time as COVID-19 is particularly interesting.

The hepatic anicteric cholestasis and cytolysis of our patient was probably due to her transplant state, as no hepatitis during COVID-19 infection was described in the literature [14] .

On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development, even when there is a high level of immunosuppression under tacrolimus treatment. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.

Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

SARS-CoV-2 Infection in Children

Epidemiology of COVID-19 Among Children in China

Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State

Coronaviruses and immunosuppressed patients. The facts during the third epidemic

Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan

Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression

Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen

Positive Epstein-Barr Virus Detection in Corona Virus Disease 2019 (COVID-19) Patients

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Epstein-Barr virus in healthy individuals from Portugal

Positive Epstein-Barr virus detection and mortality in respiratory failure patients admitted to the intensive care unit

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

We thank the family for allowing us to publish this case report.