Analysis of Adverse Effects of COVID-19 Vaccines in Spain following Booster Dose.

The present study evaluates the adverse effects of three vaccines: AstraZeneca (Vaxzevria), Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) according to the dose. From 733 participants collected, the vaccine schedule was as follows: 330 (45%) received a double dose of the AstraZeneca vaccine, 382 (52.1%) received a double dose of Pfizer, 18 (2.5%) received a heterologous prime boost and 3 (0.4%) received a single dose. Pfizer and Moderna vaccines were administered as a third dose in 70 and 121 individuals, respectively. Local and systemic reactions observed in the three vaccines were mild to moderate in severity. Only one AstraZeneca recipient (0.3%) presented a serious adverse effect: blurred vision. Adverse events were more frequent after the first dose of AstraZeneca and after the second dose of Pfizer. As the third dose, Moderna causes more adverse effects than Pfizer regardless of the type of vaccine previously administered, whereas the reactogenicity of a third dose of Pfizer is slightly higher in the group previously vaccinated with Pfizer than in that group with AstraZeneca. In short, secondary effects of the third dose of COVID-19 vaccines were similar to those after dose 2, but their frequency depends on the type of vaccine and the combinations of vaccines.

The Impact of Severe Acute Respiratory Syndrome Coronavirus Type 2 on Children With Liver Diseases: A Joint European Society for Pediatric Gastroenterology, Hepatology and Nutrition and Society of Pediatric Liver Transplantation Position Paper.

ABSTRACT: Children are seldom affected by severe forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) infection; however, the impact of comorbidities in the clinical presentation and outcome of SARS-CoV2 in children is poorly characterized including that of chronic liver disease (CLD) and those taking immunosuppressive medications for autoimmune liver disease or following liver transplantation (LT). Although not the main target organ, a spectrum of liver involvement has been described in children infected with SARS-CoV2 and those presenting with Multisystem Inflammatory Syndrome in Children (MIS-C). The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) present an evidence-based position paper on liver involvement in children with SARS-CoV2 infection and its impact on those with CLD as well as LT recipients. All children may exhibit acute liver injury from SARS-CoV2 infection, and those with CLD and may experience hepatic decompensation. Preventative and therapeutic measures are discussed.

Acute Liver Injury Among Pediatric Liver Transplantation Recipients With Coronavirus Disease 2019: An International Collaborative Study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic. The occurrence of acute liver injury (ALI) has been reported in liver transplant (LT) recipients; however, the findings on children remain controversial. This is the first extensive, worldwide report on the impact of COVID-19 on pediatric LT recipients. Our online survey reported 110 pediatric LT recipients with severe acute respiratory syndrome coronavirus 2 infection. Of these, 37 were symptomatic and 20 out of them (54%) had complicated COVID-19, which included ALI and acute liver graft rejection. No mortality was reported. Pediatric LT recipients who had undergone transplantation less than 6 months before contracting COVID-19 had a greater number of hospital admissions and a higher ALI frequency (P = 0.013 and P = 0.033, respectively) than those who had undergone transplantation more than 6 months prior. Our study found that COVID-19 cases among pediatric LT recipients demonstrated a high complication rate. We propose that these patients must be followed up strictly.

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Liver involvement in children with SARS-COV-2 infection: Two distinct clinical phenotypes caused by the same virus.

BACKGROUND AND AIMS: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) associated acute liver injury (ALI) has been linked to poor outcomes in adults. Here we compare characteristics in children with elevated ALT (E-ALT) in two distinct manifestations of the infection, multisystem inflammatory syndrome-children (MIS-C) and coronavirus disease 2019 (COVID-19). METHODS: This is a retrospective study of patients ≤21 years of age with positive for SARS-CoV-2 PCR. E-ALT was defined as alanine aminotransferase (ALT) > 40 U/L. Bivariate analysis and multivariable logistic regression were obtained to describe differences in children with and without E-ALT in COVID-19 and MIS-C. RESULTS: E-ALT was detected in 36% of the 291 patients; 31% with COVID-19, and 51% with MIS-C. E-ALT in COVID-19 was associated with obesity (P < .001), immunocompromised status (P = .04), and chronic liver disease (P = .01). In the regression models, E-ALT in COVID-19 was associated with higher c-reactive protein (OR 1.08, P = .01) after adjusting for common independent predictors. Children with E-ALT and MIS-C were more often boys (P = .001), Hispanic (P = .04), or Black (P < .001). In MIS-C, male gender (OR 5.3, P = .02) and Black race (OR 4.4, P = .04) were associated with increased odds of E-ALT. Children with E-ALT in both cohorts had significantly higher multiorgan dysfunction, longer hospitalization, and ICU stay. Children with MIS-C had 2.3-fold increased risk of E-ALT compared to COVID-19. No association was found between E-ALT and mortality. CONCLUSION: E-ALT with SARS-CoV-2 presents as elevated transaminases without hepatic synthetic dysfunction. Patients with either manifestation of SARS-CoV-2 infection and E-ALT experienced more severe disease.

Acute Hepatitis Is a Prominent Presentation of the Multisystem Inflammatory Syndrome in Children: A Single-Center Report.

BACKGROUND AND AIMS: A newly recognized multisystem inflammatory syndrome in children (MIS-C) has had a paradigm-shifting effect on the perception of severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) illness severity in children. We report the clinical and biochemical features of liver involvement, and the comorbidities that present with hepatitis, in a substantial cohort of patients. APPROACH AND RESULTS: This is a retrospective cohort study of 44 patients with MIS-C admitted at Morgan Stanley Children's Hospital of New York-Presbyterian during April and May 2020. We evaluated the number of patients who developed hepatitis and examined both demographics and inflammatory laboratory values to ascertain those that were at higher risk for liver involvement and more severe disease. Hepatitis was present in 19 subjects (43%) and was associated with more severe disease. Persons with hepatitis had significantly higher rates of shock at presentation (21.1% vs. 0%; P = 0.008), greater respiratory support requirement (42.1% vs. 12%; P = 0.005), and longer hospitalization times (median, 7 [interquartile range {IQR}, 5, 10] vs. 4 days [IQR, 3.5, 6.5]; P < 0.05). Patients with hepatitis also had significantly higher levels of ferritin (706.9 vs. 334.2 mg/mL; P < 0.01), interleukin-6 (233.9 vs. 174.7 pg/mL; P < 0.05), troponin (83.0 vs. 28.5 ng/L; P < 0.05), and B-type natriuretic peptide (7,424.5 vs. 3,209.5 pg/mL; P < 0.05). The single patient with liver failure also developed multiorgan failure requiring vasopressors, hemodialysis, and mechanical ventilation. All patients were discharged, though >50% had persistent hepatitis up to 1 month after discharge. CONCLUSIONS: Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests in many. Despite the positive outcomes reported here, close follow-up is warranted given the limited knowledge of the long-term impact of SARS-CoV-2 on the liver.

A case of an Infant with SARS-CoV-2 hepatitis early after liver transplantation.

We present a case of a pediatric liver transplant recipient diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection four days after receiving a living donor liver allograft from her mother. The recipient was a 6-month-old with end-stage liver disease due to biliary atresia and failed Kasai. The infant had an uncomplicated implantation, excellent graft function and down-trending liver enzymes until developing fevers, diarrhea, and moderate respiratory distress requiring non-invasive respiratory support. SARS-CoV-2 testing (nasal swab Polymerase Chain Reaction) was positive on post-operative day (POD) 4. Liver enzymes peaked ~1000 U/L (5-fold higher than the previous day) on POD 6. Histology demonstrated a mixed picture of moderate acute hepatitis and classical elements of mild to moderate acute cellular rejection. Her hepatitis and respiratory symptoms improved coincident with completing treatment with hydroxychloroquine, reduced immunosuppression, and intravenous gamma globulin (IVIG).

COVID-19 Associated Hepatitis Complicating Recent Living Donor Liver Transplantation.

We present a case of COVID-19 hepatitis in a living donor liver allograft recipient whose donor subsequently tested positive for COVID-19. The patient is a female infant with biliary atresia (failed Kasai procedure). She recovered well, with improving liver function tests for 4 days. On post-operative day (POD) 4 the patient developed respiratory distress and fever. COVID-19 testing (polymerase chain reaction) was positive. Liver function tests increased approximately 5-fold. Liver biopsy showed moderate acute hepatitis with prominent clusters of apoptotic hepatocytes and associated cellular debris. Lobular lymphohistiocytic inflammation was noted. Typical portal features of mild to moderate acute cellular rejection were also noted.