Doctors Petter Brodin and Moshe Arditi yesterday published a scientific study in the prestigious medical journal The Lancet in which they investigated the causes of several of the detected cases of the disease of unknown origin.
“Viruses of hepatitis A, B, C, D and E have not been found in these patients, but 72% of children with severe acute hepatitis in the UK who were tested for an adenovirus had an adenovirus detected, and of 18 subtyped cases in the UK, all were identified as adenovirus 41F. This is not an uncommon subtype but predominantly affects young children and immunocompromised patients. However, to our knowledge, adenovirus 41F has not previously been reported to cause severe acute hepatitis,” they clarified.
They then indicated that the SARS-CoV-2 it was identified in 18% of reported cases in the UK and 11% of 97 cases in England with available data who tested positive for SARS-CoV-2 on admission; three other cases had tested positive in the 8 weeks prior to admission.
“Ongoing serological testing is likely to show an increased number of children with severe acute hepatitis and previous or current SARS-CoV-2 infection. 11 of the 12 Israeli patients were reported to have had COVID-19 in recent months, and the majority of reported hepatitis cases were in patients too young to be eligible for COVID-19 vaccines. SARS-CoV-2 infection can lead to the formation of a viral reservoir,” they explained.
And they added: “The viral persistence of SARS-CoV-2 in the gastrointestinal tract can lead to repeated release of viral proteins across the intestinal epithelium, leading to immune activation. Such repeated immune activation could be mediated by a superantigen motif within the SARS-CoV-2 spike protein that resembles staphylococcal enterotoxin B, triggering a broad and nonspecific activation of T cells. by superantigens has been proposed as a causal mechanism of multisystem inflammatory syndrome in children,”
The authors clarified that there have been reports of hepatitis in children with multisystem inflammatory syndrome, but co-infection with other viruses was not investigated. “We hypothesized that recently reported cases of severe acute hepatitis in children could be a consequence of adenovirus infection with intestinal trophism in children previously infected with SARS-CoV-2 and carriers of viral reservoirs,” they noted.
The experts pointed out that in mice, adenovirus infection sensitizes to subsequent toxic shock mediated by staphylococcal enterotoxin B, leading to liver failure and death. “This finding was explained by adenovirus-induced type 1 immune bias, which, following subsequent administration of staphylococcal enterotoxin B, led to excessive IFN-γ production and IFN-γ-mediated apoptosis of hepatocytes,” they noted.
“Translated to the current situation, we suggest investigating SARS-CoV-2 persistence in faeces, T-cell receptor diversion, and IFN-γ upregulation in children with acute hepatitis, because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitized host. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis,” the researchers concluded.
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