Doctors and scientists around the world continue to investigate cases of severe hepatitis of unknown origin that continue to increase around the world. Affected patients already add 450, according to a report released by the European Center for Disease Prevention and Control (ECDC), almost 100 more than the 348 reported by the World Health Organization (WHO) in its latest report this week.
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.
“Recently, there have been reports of children with a severe acute form of hepatitis in the UK, Europe, the US, Israel and Japan. Most patients present with gastrointestinal symptoms and then progress to jaundice and, in some cases, acute liver failure. Until now, No common environmental exposures have been found and an infectious agent remains the most plausible cause.” the researchers maintained.
“Hepatitis A, B, C, D and E viruses 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 one adenovirus detected, and of 18 subtyped cases in the United Kingdom, all were identified as adenovirus 41F. This is not an uncommon subtype but predominantly affects young children and immunocompromised patients. However, as far as we know, Adenovirus 41F has not previously been reported to cause severe acute hepatitis.” they clarified.
Next, they stated that SARS-CoV-2 was identified in 18% of reported cases in the UK and in 11 (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 most of the 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. The viral persistence of SARS-CoV-2 in the gastrointestinal tract can lead to the repeated release of viral proteins through 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”, they maintained.
Paradoxically, the authors clarified that acute hepatitis has been reported in children with multisystem inflammatory syndrome, but coinfection with other viruses was not investigated. And they came to the following conclusion: “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.”
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 result was explained by adenovirus-induced type 1 immune bias, which, after subsequent administration of staphylococcal enterotoxin B, led to excessive IFN-γ production and IFN-γ-mediated apoptosis of hepatocytes,” they clarified.
“Translated to the current situation, we suggest that SARS-CoV-2 persistence in faeces, T-cell receptor diversion, and IFN-γ upregulation in children with acute hepatitis be investigated, because this could provide evidence. of a SARS-CoV-2 superantigen mechanism in a host sensitized with adenovirus-41F. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis,” the researchers concluded.
The hypotheses that link acute hepatitis in boys with COVID-19
In this context, The WHO announced that it is working on several hypotheses to determine the origin of acute childhood hepatitis and specified that three of them are linked to the coronavirus.
In parallel, the medical journal The Lancet published on Friday a study by doctors Petter Brodin and Moshe Arditi, in which the causes of several of the detected cases of the disease of still unknown origin were investigated.
The report gives an account of the cases registered in the United Kingdom, Europe, the United States, Israel and Japan, and makes general considerations first. “Most patients present with gastrointestinal symptoms and then progress to jaundice and, in some cases, acute liver failure,” say the scientists.
“So far, no common environmental exposures have been found and an infectious agent remains the most plausible cause,” they held.
They then stated that the SARS-CoV-2 virus was identified in 18% of reported cases in the UK; 11 (11%) of the 97 cases from England tested positive on admission; and three other cases had tested positive in the previous 8 weeks.