Long COVID-19 Liver Manifestation in Children

Abstract

Objectives: Severe acute respiratory syndrome coronavirus 2 , the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. Methods: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. Results: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. Conclusions: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.

Adeno-associated virus 2 infection in children with non-A-E hepatitis

“…In the recent outbreaks of unexplained hepatitis in children, it has been inconsistently reported. [4][5][6][19][20][21] HHV6B is a human herpesvirus that is associated with the childhood illness roseola infantum (sixth disease) and a self-limiting otherwise non-specific febrile illness. 22 Seroconversion usually occurs by 2 years of age and hepatitis occasionally occurs in immunocompetent individuals.…”

Mysterious cases of acute hepatitis in children: is adenovirus still a lead suspect?

“…However, evidence for the hepatic tropism of SARS-CoV-2 and molecular signature data from the characterization of associated liver injury provides strong incentive to pursue further study in this area [ 13 ]. The recently published report on documented long COVID-19 liver manifestations in children [ 14 ] adds significant fuel to the ongoing debate. Importantly, an additional mechanism has been proposed, where release of viral proteins across the intestinal epithelium may mediate a superantigen motif in the SARS-CoV-2 spike protein, in adenovirus-sensitized hosts [ 15 ] which also warrants further investigation.…”

Mysterious child hepatitis continues to vex researchers

“…On 10 June, Waisbourd-Zinman published a case series concerning five children with un explained hepatitis 3 . Only one of them, she says, tested positive for adenovirus.…”