Hepatitis Cases Mount, And So Do The Theories

Yet The Answer To The Question Of Cause Remains "I Do Not Know"

It has now been a month since the start of a global outbreak of hepatitis in a cohort of patients with the lowest incidence of liver disease, very young children. If anything, less seems known now than at the start of the outbreak.

While adenovirus has been detected in a majority of US cases identified by the CDC, and sequencing has indicated the particular strain to be type 41, known to cause gastrointestinal symptoms, doctors are far from certain it is the cause of the liver disease.

Nearly half of the children identified by the CDC also have tested positive for adenovirus, a common bug among kids that usually causes severe stomach illness and pink eye. CDC officials are casting a wide net as they search for a cause but on Wednesday the agency said that adenovirus infection “continues to be a strong lead.”

Adenovirus has also been detected in around 70% of cases identified in the UK, yet even in the UK doctors are refraining from asserting a clear causative role for adenovirus in the hepatitis cases.

"Over the last week, there's been some important progress with the further investigations and some refinements of the working hypotheses," Philippa Easterbrook, from the WHO's global hepatitis programme, told a press conference.

One reason doctors are uncertain about adenovirus type 41: known indicators of adenovirus-related liver damage or disease are not being found in this cases linked to this hepatitis outbreak.

None of the U.K. liver samples " … show any of the typical features you might expect with a liver inflammation due to adenovirus but we are awaiting further examination of biopsies," Easterbrook added.

COVID Related?

Even though only around 18% of patients have tested positive for an active SARS-CoV-2 infection, doctors are taking a closer look at a possible role for COVID, perhaps in the form of a lingering “long COVID” effect of a prior and no longer active infection.

"At present, the leading hypotheses remain those which involve adenovirus, with also still an important consideration about the role of Covid as well, either as a co-infection or a past infection," Easterbrook said.

One hypothesis for the involvement of past COVID infection described in The Lancet centers on a residual presence of virus in the intestines—what researchers are labelling as “viral reservoirs”.

SARS-CoV-2 has been identified in 18% of reported cases in the UK and 11 (11%) of 97 cases in England with available data tested SARS-CoV-2 positive on admission; a further three cases had tested positive within the 8 weeks prior to admission.2 Ongoing serological testing is likely to yield greater numbers of children with severe acute hepatitis and previous or current SARS-CoV-2 infection. Eleven of 12 of the Israeli patients were reported to have had COVID-19 in recent months,3 and most reported cases of hepatitis were in patients too young to be eligible for COVID-19 vaccinations. SARS-CoV-2 infection can result in viral reservoir formation.4 SARS-CoV-2 viral persistence in the gastrointestinal tract can lead to repeated release of viral proteins across the intestinal epithelium, giving rise to immune activation.5 Such repeated immune activation might be mediated by a superantigen motif within the SARS-CoV-2 spike protein that bears resemblance to Staphylococcal enterotoxin B,6 triggering broad and non-specific T-cell activation. This superantigen-mediated immune-cell activation has been proposed as a causal mechanism of multisystem inflammatory syndrome in children.4, 7

The reference to Israeli patients is particularly noteworthy, owing to recent research from Israel of wastewater data regarding levels of fecal shedding of the SARS-CoV-2 virus. While that study’s conclusions were considered specious and probably wrong by no less a viral authority than Geert Vanden Bosche, the data gathered was not entirely without value. As fellow Substack writer Igor Chudov has detailed, the data confirmed an ongoing presence of the virus in the gut, indicating an inability of COVID patients to fully clear the virus.

… highly vaccinated Israel is beset with Chronic Covid, and that people who seem to have recovered from Covid, are still sick and have ongoing active Covid infections that they picked a long time ago.

I myself had significant criticisms of the Yaniv wastewater study, owing to methodological defects and questionable base assumptions.

Israeli Wastewater Study A Study In Junk Science

Yet, to the extent the data can be trusted, the presence of SARS-CoV-2 virus in wastewater confirms the virus does express itself within the GI tract, and, as Igor demonstrated, can reside there for some time, leading to gut-related “post-acute COVID-19” gastrointestinal symptoms.

We report expression of SARS-CoV-2 RNA in the gut mucosa ∼7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8+ T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19, immunosuppressive therapy and gut inflammation. We were unable to culture SARS-CoV-2 from gut tissue of patients with viral antigen persistence. Post-acute sequelae of COVID-19 were reported from the majority of patients with viral antigen persistence, but not from patients without viral antigen persistence.

Post-acute COVID infection has already been identified as involved in multisystem inflammatory syndrome. The authors of the Lancet “superantigen” study hypothesize that post-acute COVID infection, coupled with adenovirus infection, overloads the immune system, causing it to overreact to the presence of adenovirus and ultimately attacking the liver—in essence, either an autoimmune response triggered by post-acute presence of SARS-CoV-2 coupled with an opportunistic infection of adenovirus type 41, or a toxic shock phenomenon from the immune system fighting off two viruses simultaneously.

Acute hepatitis has been reported in children with multisystem inflammatory syndrome, but co-infection of other viruses was not investigated.8 We hypothesise that the recently reported cases of severe acute hepatitis in children could be a consequence of adenovirus infection with intestinal trophism in children previously infected by SARS-CoV-2 and carrying viral reservoirs (appendix). In mice, adenovirus infection sensitises to subsequent Staphylococcal-enterotoxin-B-mediated toxic shock, leading to liver failure and death.9 This outcome was explained by adenovirus-induced type-1 immune skewing, which, upon subsequent Staphylococcal enterotoxin B administration, led to excessive IFN-γ production and IFN-γ-mediated apoptosis of hepatocytes.9 Translated to the current situation, we suggest that children with acute hepatitis be investigated for SARS-CoV-2 persistence in stool, T-cell receptor skewing, and IFN-γ upregulation, because this could provide evidence of a SARS-CoV-2 superantigen mechanism in an adenovirus-41F-sensitised host. If evidence of superantigen-mediated immune activation is found, immunomodulatory therapies should be considered in children with severe acute hepatitis.

Thus COVID infection may yet prove to play a role in the hepatitis outbreak—not from an active infection but from post-acute persistence of the virus within the intestines. Hepatitis arising from such COVID phenomena, whether brought on by an autoimmune response or by toxic shock, would mark a major increase in the potential severity and seriousness of lingering post-acute COVID infection.

Still No Correlation To COVID Inoculation

While there continues to be a level of suspicion on social media that the much-maligned (and justly so!) COVID inoculations are somehow involved, the reported clinical data has yet to yield evidence of any demonstrable link between the inoculations and the hepatitis outbreak. The stumbling block is simple: by far the majority of pediatric hepatitis cases are in patients too young to receive the inoculations.

Because adenoviruses are used in some of the COVID-19 vaccinations, one theory on social media suggested a link between the jab and the hepatitis outbreak in the U.K., where most of the cases have been reported, according to Reuters.

But these adenoviruses in the vaccines are "harmless transporters which have been modified so they cannot replicate or cause infection," according to BBC News.

"There is no evidence of any link to the coronavirus (COVID-19) vaccine. The majority of cases are under 5 years old, and are too young to have received the vaccine," the U.K. Health Security Agency (UKHSA) said.

Of course, the eternal caveat remains that absence of evidence is not evidence of absence. While the possibility of the inoculations playing a role is at this point increasingly unlikely, it is not possible to exclude them absolutely.

However, the possibility of the lunatic lockdowns having stunted immune system development among children due isolation and social distancing limiting otherwise routine exposure to environmental pathogens remains an actively considered hypothesis.

Prof McConkey told Pat Kenny he believes social distancing, as a result of the pandemic, may have played a part.

"It could be a link to the social distancing we've all had.

"We've all been sort of not physically interacting with as many people for the last couple of years.

"So little children haven't been getting their usual childhood exanthems - their fevers, and snotty noses that children normally get in the first couple of years of life.

The reality of childhood illness is that it is the primary means of “teaching” the human immune system about environmental pathogens, and shielding children from all potential illnesses is fraught with its own health risks and consequences.

The possibility that a consequence for some children of enduring the lunatic lockdowns is a diseased and failed liver is real enough for doctors to seriously consider it. It is unequivocally a possibility that cannot be ignored.

There Is No Magic Wand

While the Lancet “superantigen” study offers some guidance on how to confirm the presence of SARS-CoV-2 viral reservoirs, which, if found often enough, could establish a consistent causative agent to explain the origins of these cases of pediatric hepatitis, as of this writing there remains no definitive explanation, no definitive “this is why” theory which has been proven to be a plausible explanation of the condition. It might involve adenovirus type 41. It might involve SARS-CoV-2 viral reservoirs in the gut. It might even involve the COVID inoculations.

As of this writing, the doctors, the WHO, and the CDC simply do not know for certain what is causing children to suddenly experience liver inflammation, hepatitis, and, tragically, death for a few.

We do well to pause to remember that liver failure in children is extremely rare, and half of all such cases historically have defied explanation—even before this rash of cases, half the time, doctors simply do not know why children develop hepatitis.

Medicine and science have done much to reduce human suffering and death from disease. Yet for all the strides both have made, both remain finite and limited—for all that is known about disease as well as the human body, there is yet much more that is not known. Medical mysteries are still very much a medical reality.

Which remains the constant cautionary lesson in every new disease outbreak, and with the appearance of every novel pathogen. For all that we know about disease, and for all that is knowable about disease, we are always stymied by the boundary between what is known and what is unknown, between what is knowable and what is as yet unknowable. Through research and investigation we push that boundary back, but we never eliminate that boundary. Ultimately, we are forever confounded by the unknown and the as yet unknowable.

Medicine and science are the means by which we push the boundary back. They are not magic wands, and they are not guarantees that no one will ever suffer from disease ever again. There are no magic wands, and neither doctors nor researchers are magicians, able to work miracles with a simple wave of the hands.

While people will never stop searching for answers to questions of medicine and of science, we must still understand, for today, the answer is most likely “I do not know.”