The Lancet Update: COVID-19 is the leading cause of acute childhood hepatitis of unknown origin, and adenovirus is an accelerating factor.
This view comes from a correspondence paper by two scholars in the Department of Immunology and Inflammation, Imperial College London, UK, and the Department of Paediatrics, Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, California, USA .
They propose that acute childhood hepatitis of unknown origin is the result of adenovirus infection combined with intestinal malnutrition in children previously infected with SARS-CoV-2 and carrying the virus reservoir.
In other words, the new coronavirus is the main cause of acute unexplained hepatitis in children, but adenovirus infection exacerbates this process, which has led to the current increase in children with unexplained hepatitis.
Why can I get this conclusion? The two authors gave their reasons.
One is that unexplained hepatitis in children is most likely caused by infection
At present, children with unexplained hepatitis have not been found to be exposed to common hepatitis pathogenic factors, such as hepatitis patients, toxic substances, or drugs that damage the liver, etc., and most children They are very young and have not been vaccinated against the new crown. Therefore, infectious causes are the most likely causes of unexplained hepatitis.
While 18% of reported cases in the UK were found to be infected with Covid-19, they believe ongoing serological testing (aka antibody testing) could be found in children with unexplained hepatitis More children who were or are currently infected with SARS-CoV-2.
PS: Some friends may be wondering, antibodies can also be produced after vaccination. Will this antibody test cause misunderstandings? How to use antibody test to distinguish between new coronavirus infection and vaccination
The antibodies produced by the vaccine are mainly against the S protein, but the antibodies produced after virus infection are against all the proteins of the virus, so screening for antibodies against other viral proteins, such as nucleocapsid proteins, , you can distinguish whether you have been vaccinated or have been infected. However, no such test kits are currently available on the market.
Second, adenovirus 41F has not been found to cause hepatitis, but the new coronavirus may cause hepatitis
Although the UK has previously attributed the cause to the adenovirus 41F subtype, this explanation is not very reliable, and this subtype has not been reported to cause severe acute hepatitis before.
And some previous findings have linked SARS-CoV-2 to acute hepatitis:
One of the authors, Peter’s previous academic review published in the journal Immunity [3], analyzed the characteristics of children infected with new crowns and found that intestinal epithelial cells will long-term discharge new coronavirus RNA . The authors believe that SARS-CoV-2 infection may form a viral reservoir in the gut.
But don’t worry, none of these viruses are live viruses and are not infectious because the virus is inactivated when released from the apical intestinal epithelial cells into the intestinal lumen.
The intestinal pant virus reservoir continuously and repeatedly releases proteins produced by the virus. These proteins are foreign substances, which will cause an immune response in the intestinal tract, and will also release the zonulin in the intestinal tract, increase the intestinal permeability, and allow the viral proteins in the intestinal tract to re-enter the bloodstream, causing a systemic immune response, leading to different Inflammation of body parts, including the heart, lungs, kidneys, brain, skin, liver, etc., is known as multisystem inflammatory syndrome in children (MIS-C).
As early as 2020, Columbia University in New York reported that acute hepatitis is a prominent manifestation of multisystem inflammatory syndrome in children. [4]
Third, adenovirus infection may exacerbate the liver damage caused by the new coronavirus
Further research on the mechanism of this systemic inflammatory response found that a certain sequence of the S protein of the new coronavirus exhibits superantigen properties and is one of the causes of multisystem inflammatory syndrome. This section of the motif with superantigen properties is unique to the new coronavirus and other coronaviruses, but its sequence and structure are highly similar to the superantigen of staphylococcal enterotoxin B. [5] That is, the arrangement order of the two components is very similar to the arrangement.
PS: What is a superantigen? It is an antigen that can cause a strong immune response in the human body at a very low concentration, and it does not pick targets when it is activated, especially to activate T cells. Common antigens are generally deactivated with certain specific immune responses, and common antigens need to reach a certain concentration.
Ordinary antigens require antigen-presenting cells (APCs) for packaging (binding in the red area), and are restricted by major histocompatibility complex (MHC) class II molecules and can only be activated A specific type of T cell; while the superantigen is directly bound to the outside, it can bind to the T cell receptor (TCR) itself, and is not restricted by MHC class II molecules, and can bind to multiple types of T cells. of.
The authors hypothesize that acute childhood hepatitis of unknown origin is the result of adenovirus infection and intestinal malnutrition in children previously infected with SARS-CoV-2 and carrying the virus reservoir.
In order to demonstrate this hypothesis, the author uses an animal experiment of the interaction of adenovirus and staphylococcal enterotoxin B as an example [6]:
This experiment found that staphylococcal enterotoxin B exposure alone did not cause significant liver damage, but co-infection with adenovirus increased the severity of liver damage following staphylococcal enterotoxin B exposure. This may be because adenovirus infection increases the absolute number of T cells in the spleen and leads to excess production of IFN-γ, which mediates hepatocyte apoptosis.
It has already been said that the superantigens of the new coronavirus are highly similar to the superantigens of staphylococcal enterotoxin B, so it is reasonable to suspect that adenovirus infection also causes a similar reaction in patients with the new coronavirus.
Author’s suggestion:
Investigation of faecal SARS-CoV-2 persistence, T-cell receptor skew, and IFN-γ upregulation in children with acute hepatitis to prove or disprove his hypothesis .
Therefore, we need to remain concerned and vigilant without undue panic for their further testing of children with unexplained hepatitis.