During the new crown epidemic, most of the children infected showed asymptomatic or mild symptoms, and only a small number of children were infected with the new coronavirus for 1-2 months Later, multisystem inflammatory syndrome(MIS) appeared, and one of the complications of MIS was acute hepatitis. In a 2020 single-center study, 44 children developed a multisystem inflammatory syndrome after COVID-19 infection, 19 of whom had acute hepatitis symptoms , 1 patient developed liver failure. It is worth noting that more than half of the children with MIS had negative nucleic acid tests on admission(56.8%), while antibody tests were positive< /span>(92.3%), indicating that patients with multisystem inflammatory syndrome are likely to have been infected with the new coronavirus, but not necessarily during the new coronavirus infection. Only 18% of children with unexplained acute hepatitis in the UK recently tested positive for the new coronavirus nucleic acid, and further serological testing can determine whether these children have ever been infected with the new coronavirus. SARS-CoV-2 spike protein(S) There is a superantigen motif on span>, which is highly similar to the sequence and structure of staphylococcal enterotoxin B superantigen. If ordinary antigens can only activate T cells with corresponding receptors, the principle of superantibody can widely activate a large number of T cells, generate inflammatory storms, and damage multiple organs, including the liver. This question is equivalent to asking why MIS is more common in children? As mentioned earlier, most children have mild symptoms after being infected with the new crown virus. In the first year of the new crown epidemic, only about 2 deaths per million new crown deaths in the UK were from patients under the age of 18, but the new crown virus caused more MIS. Seen in children and rarely in adults. An interesting explanation is the energy distribution trade-off theory, which states thatchildren who are in the growing stage tend to devote more energy to their own development if they become infected with a virus. If a severe inflammatory reaction occurs and consumes a lot of energy, the body will choose to coexist with the virus, rather than immediately launch an immune response to attack the virus. Petter Brodin recommends stool testing for SARS-CoV-2 in these children with severe hepatitis There is T cell receptor skew and upregulation of IFN-γ consistent with superantigen activation.If the hypothesis that SARS-CoV-2 superantigen causes severe hepatitis is true, treatment with steroids and immunoglobulins or other immunomodulators , may be able to save these children with severe hepatitis.References 1.Brodin P, Arditi M. Severe acute hepatitis in children: investigate SARS-CoV-2 superantigens [published online ahead of print, 2022 May 13]. Lancet Gastroenterol Hepatol. 2022;S2468-1253(22)00166-2. doi:10.1016/S2468-1253(22)00166-2 2.Brodi n P. SARS-CoV-2 infections in children: Understanding diverse outcomes. Immunity. 2022;55(2):201-209. doi:10.1016/j.immuni.2022.01.014 3. Cantor A, Miller J, Zachariah P, DaSilva B, Margolis K, Martinez M. Acute Hepatitis Is a Prominent Presentation of the Multisystem Inflammatory Syndrome in Children: A Single-Center Report. Hepatology. 2020;72( 5):1522-1527. doi:10.1002/hep.31526 4.Yarovinsky TO, Mohning MP, Bradford MA, Monick MM, Hunninghake GW. Increased sensitivity to staphylococcal enterotoxin B following adenoviral infection. Infect Immun. 2005;73(6):3375-3384. doi:10.1128/IAI.73.6.3375-3384.2005 5. Cheng MH, Zhang S, Porritt RA, et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci U S A. 2020;117(41):25254-25262. doi :10.1073/pnas.2010722117Since the UK first notified WHO of 10 cases of acute severe hepatitis of unknown origin in Scotland on 5 April, the UK, US, Israel, Japan, Spain, Denmark More than 300 cases have been reported in 12 EU countries including China, the Netherlands and Sweden. As of the beginning of May, 18 children have been treated with liver transplantation, and more than 5 cases have died. The possibility of hepatitis virus infection, exposure to toxic substances or drug-induced hepatitis has been ruled out, however, 72% of UK cases tested positive for adenovirus, of which 18 children underwent adenovirus subtype analysis, All without exception are adenovirus type 41. February-April is the peak period of adenovirus epidemic, and children are also susceptible to adenovirus, but patients with adenovirus type 41 infection usually present with diarrhea, vomiting and fever, accompanied by respiratory symptoms, almost Does not cause liver failure. Not only that, in the case of Alabama, USA, adenovirus was only found in the blood of the child, and the presence of adenovirus was not detected in the liver. Therefore, some medical experts believe that adenovirus infection is not the direct cause of severe hepatitis. The real killer of severe hepatitis is someone else. Adenovirus is only an accomplice or innocent person involved in the storm span>(just in time for the peak of the adenovirus epidemic). Recently, Petter Brodin, a paediatric immunologist from Imperial College London, UK, published his latest hypothesis in The Lancet Gastroenterology and Hepatology, proposingCOVID-19 Viral superantigens may be the real cause of acute severe hepatitis in children.
Mechanism of MIS caused by novel coronavirus
Why is severe hepatitis only seen in children?
On the 34th day after the child was infected with the new crown, the feces could still be detected (only the new crown nucleic acid fragment was detected on the 19th day in adults) /span>, if the new coronavirus persists in the intestine, it will continuously release superantigens, resulting in an inflammatory response, which in turn leads to damage to the intestinal mucosal barrier, superantigens enter the blood circulation, and cause MIS.
Another explanation is thata virus commonly found in children is able to act synergistically with the SARS-CoV-2 superantigen , which causes MIS, and this virus is adenovirus type 41.A 2005 study in mice demonstrated that adenovirus infection enhanced the sensitivity of mice to staphylococcal enterotoxin B superantigen, resulting in Liver failure and death in mice. If a child is infected with adenovirus and then infected with 2019-nCoV, or if 2019-nCoV exists in the body for a long time, MIS may theoretically occur, resulting in severe hepatitis.
How to verify that SARS-CoV-2 superantigen causes severe hepatitis
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