Acute hepatitis with unknown etiology amidst the COVID-19 and monkeypox time: an emerging global concern among the children

Dear Editor, Many countries are reporting cases with acute severe hepatitis without any identifiable cause among young children. This sudden surge of cases has been observed after the WHO published disease outbreak news on 23 April 2022. It may be due to sudden increase in severe hepatitis cases after COVID-19 pandemic or due to increase in awareness and laboratory testing for hepatitis. According to theWHO report, approximately all cases were in the range of 1 month to 16 years of age. Among which nearly 10% required liver transplantation and one mortality was reported. In European countries, 75.4% of the cases are aged below 5 years and are mostly clustered between 1 month and 16 years of age. These children are presenting with symptoms of abdominal pain, diarrhea, vomiting, acute hepatitis with elevated liver enzymes (aspartate transaminase, alanine transaminase greater than 500 IU), and mild jaundice. Fever was absent in the majority of cases and serology for the commonly known hepatotropic viruses causing hepatitis-like hepatitis A, B, C, D, E viruses was also negative, thus the exact pathophysiology and mode of transmission are still unclear. Currently, around 74 cases were found positive for adenovirus which on further molecular testing was identified as type F41 among 18 of the total cases. SARS-CoV-2 was identified in 20 and 19 cases were detected with a SARS-CoV-2 and adenovirus co-infection, the etiology is accepted to be adenovirus type F41 and many countries are also reporting enhanced community circulation of adenoviruses. Adenoviruses often cause minor respiratory symptoms; however, they have previously been linked to hepatitis in immunocompromised children. In this context, a recent WHO report showed that out of 63 cases with data available on COVID-19 vaccination status, 53 (84.1%) were not vaccinated. This might be due to an undetected latent SARSCoV-2 infection that is now manifesting as CAH (COVID-19acquired hepatitis). It is further supported by the fact that post COVID liver injuries are also being reported in adults as well. In a study, two pediatric patients presenting with post COVID-19 hepatic symptoms underwent liver biopsies and the explant of two infants requiring liver transplant shows massive necrosis along with bile duct proliferation and lymphocytic infiltrate was evident. Some researchers believe that previous exposure to SARS-CoV-2 genetic variants like B.1.1.529 may have enhanced the risk of severe hepatitis. They reported at least one acute severe hepatitis case among 12 of 39 countries included in the study and number of confirmed SARS-CoV-2 genetic variant (mostly Omicron B.1.1.529 variant) cases in these 12 countries found to be between 4.4 and 11.9 million. Of 181 cases, 60.8% were positive for adenovirus, 12.2% cases positive for SARS-CoV-2 ,and it was observed that 133 cases were positive for both the viruses. Population-based serological testing in the affected countries will probably show a greater number of children suffering from acute severe hepatitis having past or recent SARS-CoV-2 infection. In a study done by Yarovinsky et al., it was reported that adenovirus infection in mice sensitizes the mice for HIGHLIGHTS • Many countries are reporting cases with acute severe hepatitis without any identifiable cause among young children. • Hepatitis may be due to sudden increase in severe hepatitis cases after coronavirus disease 2019 (COVID-19) pandemic or due to increase in awareness and laboratory testing for hepatitis. • As a preventive action, COVID-19 vaccination should be encouraged globally in healthy children to break the possible chain of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in communities.