In silico study may explain the rise of hepatitis among children

Posted on by Jesse Santiano, M.D.

You may have heard of the unexplained rise in liver inflammation or hepatitis among children. In a report by Yale Medicine,

Yet more than 100 cases of severe hepatitis—in otherwise healthy children—have been reported in 25 states and territories in recent months.

And there have been at least another 100 cases in 19 other countries. While most children fully recover from hepatitis, 14% of the cases in the U.S. require a liver transplant, and five children have died, according to the Centers for Disease Control and Prevention (CDC).

In the same Yale article, COVID-19 and its vaccines may not have anything to do with hepatitis in children since even those less than five years old are affected. Instead, scientists believe that another virus, the adenovirus causes hepatitis.

A preprint study from the Chinese Academy of Sciences may provide an answer to the mystery. Their experiment analyzed all the available genetic sequences of the SARS-CoV-2 in GISAID. They found 170 strains of SARS-CoV-2 with mutations that made them similar to a human protein. The modifications have been detected in fifteen countries across five continents. 

Those mutations are in the Open Reading Frame 1ab (ORF1ab).  ORF1ab functions in viral replication and is not part of the spike protein. The image below shows the genetic sequence of the SARS-CoV-2. Notice that the ORF1ab is separate from the spike protein.

In Silico Study May Explain The Rise Of Hepatitis Among Children
By Furfur – Own Work, Using Ncbi Orf Finder Genbank: Wu,F., Zhao,S. Et Al. A Novel Coronavirus Associated With A Respiratory Disease In Wuhan Of Hubei Province, China. Accession Mn908947., Cc By-Sa 4.0, Https://Commons.wikimedia.org/W/Index.php?Curid=86175627

In any infection, the body develops an immune response to the different parts of the attacking microorganism. In the case of COVID-19, antibodies and T cells are produced against the many proteins of the SARS-CoV-2, including the spike protein and the ORF1ab.

In the study, mutations in the ORF1ab made it similar to the human protein PAPR14 in the liver. What happens next is that an autoimmune response occurs, and inflammation results. Since the PAPR14 protein is in the liver, the resulting inflammation is called hepatitis.

Their findings are consistent with the occurrence of the ORF1ab mutations detected in the United Kingdom and the USA.

To test their autoimmune hypotheses, they used a binding prediction tool to determine if the T cells produced in response to the mutations in the ORF1ab will also attack the PARP14 – the results showed that those T cells produced in repose to the mutated SARS-CoV-2 could also bind PARP14. 

Why are children mostly affected?

The immune system always encounters similarities between “self” proteins and “non-self” or foreign proteins that we inhale or ingest. However, a mature immune system has a mechanism to prevent an autoimmune response.

The authors explained that the thymus, where T cells come from, is still developing and learning to sort out “self” and “non-self” proteins in children. Therefore, if they get COVID-19 at a young age, the risk of autoimmunity is higher.

Another explanation from the authors is that COVD-19 infection has been known to alter the T cell response, leading to an autoimmune response.

This study is preliminary but provides a direction where future studies can be made to understand better and prevent hepatitis.

This study does not show any connection between the COVID injections and hepatitis. Another study explains that. You can read about how the Pfizer mRNA jab can cause autoimmune liver hepatitis at Pfizer COVID shot makes human liver cells produce SARS-CoV-2 spike DNA.

 

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Reference:

Yu Wang, Yuexing Liu. SARS-CoV-2 ORF1abA1061S potentiate autoreactive T cell responses via epitope mimicry: an explanation to hepatitis of unknown cause. 
bioRxiv 2022.05.16.491922; doi: https://doi.org/10.1101/2022.05.16.491922