COVID-19 Associated Hepatitis in Children (CAH-C) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon

Abstract

Background: Besides Covid-19, SARS-CoV-2 infection has been associated with Multiple Inflammatory Syndrome in children (MIS-C). However, a unique presentation of a transient form of hepatitis in pediatric age group occurring subsequent to the asymptomatic SARS-CoV-2 infection is yet to be reported in children. Presently the clinical work, temporal association and characteristics different than MIS-C of the cases of CAHC is being dealt with. Methods: As a retrospective and follow up observational study we reviewed all pediatric patients presenting with acute hepatitis during the study period from April 2021 to mid- June 2021. We observed a sudden rise of features of hepatitis in a group of pediatric patients during the second wave of SARS CoV-2 infections, where children or adolescents developing sudden onset acute hepatitis with no history of pre-existing liver disease in the absence of familiar etiology of acute hepatitis and with a recent 3-6 week history of RT-PCR positivity or a retrospectively proven Covid-19 infection with high titer SARS CoV-2 antibodies. Such patients had asymptomatic Covid-19 infection, while another very small group (n=8) patients having findings similar to MIS-C was identified with protracted and grave presentation, having multiple organ involvement along with Covid-19 diagnosis. Routine lab workup along with viral serology of acute hepatitis was performed in all such patients. These patients were negative for Hepatitis A, B, C and E but had high titer of SARS CoV-2 antibodies. Results: Among 33 patients who presented with hepatitis, 25 patients showed unique features of CAHC, they had hepatitis only. These patients did not have any typical Covid-19 symptoms, had normal to borderline inflammatory markers, with admission to general care wards, all recovered on supportive treatment without any complications or mortality. Whereas patients with MIS-C (n=8) required admission to critical care, they had high level of inflammatory markers and 3 (37.5%) had an adverse outcome. Conclusion: With emergence of newer variants of concern such as the Delta variant which caused the massive wave of Covid-19 in India, with varied presentations, CAHC is one of them. Such new entities need to be timely identified and differentiated from other types of emerging syndromes in children for appropriate management.

Severe Acute Hepatitis in Children of Unknown Etiology

“…18 However, when one considers both evidence of acute and previous infection, the strength of association may increase. In a preprint from India, 19 among 37 cases of hepatitis between April -July 2021, all were either infected with or had prior evidence of SARS-CoV-2 infection. Furthermore, from the European surveillance data, while serology results were only available on 26 cases, 19 (73.1%) were seropositive.…”

“…19,25 A preprint report of a nationwide (US) retrospective cohort study from March 11, 2020 to March 11, 2022 of 245,675 children with a history of COVID-19 (≤10 years old, mean age: 6.0 ± 3.1 years),26 found that children with COVID-19 had a higher risk of elevated AST or ALT (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 2.03-3.12) and bilirubin (HR: 3.35, 95% CI: 2.16-5.18) at six months after infection compared with a propensityscore matched cohort of those with other respiratory virus infections (n= 245,161).…”

Elevated liver enzymes and bilirubin following SARS-CoV-2 infection in children under 10

“…1,2 Early evidence from a study in India described 37 pediatric patients presenting with clinical signs of hepatitis after having COVID-19, but how COVID-19 affects the liver in pediatric patients remains unknown. 3 Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. 4 In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children.…”

Emerging cases of acute hepatitis of unknown origin in children amid the ongoing COVID-19 pandemic: Needs attention – Correspondence

“…Another possibility is both adenovirus and coronavirus infecting the same child may lead to a totally different virus that has not been detected yet ( https://theconversation.com/hepatitis-cases-are-increasing-among-children-in-the-uk-could-covid-have-a-role-to-play-181303 ). A recent study from India suggested that either the Delta variant or its interaction with adenovirus or newer recombinants of Delta variant may possibly be associated with pediatric hepatitis which needs urgent and thorough investigations [ 10 ]. Another possible reason is autoimmune hepatitis (the body itself attacks the liver); however it is also a rare condition that is causing a cluster of cases in children.…”

“…Some asymptomatic SARS-CoV-2 infection in children or adolescents (n = 33) developed into acute hepatitis with no history of pre-existing liver disease. The patients (n = 8) with MIS having a high level of inflammatory markers which required admission to critical care, and three patients had an adverse outcome [ 13 ]. Pessoa and his coworkers have reported the first case of hepatitis in a male child infected with SARS-CoV-2 that has the Toll-like receptor 7 (TLR-7) Gln11Leu single nucleotide polymorphism, which could impair an efficient initial immune response [ 14 ].…”