Between April and July of this year, 1,010 cases of severe hepatitis without any explicable cause were reported in children in more than 35 countries. Nearly half of these cases were in Europe, including more than a quarter in the UK.
Usually, hepatitis in children is caused by infection with one of the hepatitis viruses (such as hepatitis A or hepatitis C). But even though children showed elevated levels of hepatitis markers in their blood, no traces of hepatitis viruses were detected in these children, nor in any of the related cases since then.
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Initial studies found a possible association between adenovirus infection and these cases of hepatitis. Adenoviruses are very common viral infections, especially in children. They usually cause infections such as a mild cold, pink eye (conjunctivitis), or stomach problems. However, if they get into the liver, in rare cases they can cause hepatitis.
Given how common adenoviruses are in children — and because they rarely cause hepatitis in healthy people — it’s hard to say that this was the likely cause.
A new study suggests the wave of severe hepatitis cases seen in children may be the result of three factors working together: adenovirus, adeno-associated virus 2 (AAV2) and an underlying genetic predisposition to the disease.
A possible cause emerges
In a pre-print study (meaning it hasn’t yet been reviewed by other scientists), a team of researchers examined nine of the original hepatitis cases in April and conducted a large number of tests to detect new or previously undetected viruses. to find. or genetic factors that may have caused hepatitis in the children.
The team found that all nine children were infected with adeno-associated virus. They then compared their findings with 13 healthy children and 12 children who had had adenovirus infections but no hepatitis. Adeno-associated virus 2 was not detected in any of these children. This was a strong indication that AAV2 was the cause of these mysterious hepatitis cases.
Adeno-associated virus 2 belongs to a group of viruses called Dependoparvovirus that infects both humans and some primates. But what’s especially interesting about AAV2 is that in order to infect the host, it needs another virus to infect the host at the same time. It uses this helper virus to replicate in human cells. The most common AAV2 helper viruses are adenovirus and herpes virus.
The researchers found that six of the nine patients they looked at had an adenovirus, while three showed signs of a herpes virus. This makes it likely that these hepatitis infections were caused by a combination of AAV2 and one of these helper viruses.
Immune Systems and Infections
But both AAV2 and infections such as adenovirus and herpesvirus are quite common in children, and most children infected with them do not develop hepatitis. This means that an additional factor must be at play here, perhaps even on a genetic level.
The team of researchers then analyzed the children’s genomes to look for specific immune system markers called human leukocyte antigens. Immune system cells use human leukocyte antigens to detect and engulf other viruses and pathogens.
This then sends a signal to other immune cells that come along and destroy the pathogen. There are many different types of human leukocyte antigens and depending on which type a person has can determine which infections they are more susceptible to.
The researchers found that eight out of nine children had a higher genetic prevalence of a certain type of person leukocyte antigen, which may have increased their chances of getting hepatitis symptoms from these viral infections. This type is also more common in people of European descent, which may further explain why these cases of hepatitis were mainly seen in Europe.
While this study suggests that a combination of factors may explain the sudden, severe cases of hepatitis in children, the study itself was small and only conducted on participants in Scotland. A much larger, peer-reviewed study will need to be done to fully determine the exact link and how best to protect children in the future.
Another factor that could have played into this was: COVID-19 limitations, which meant that many children were not exposed to these viruses and developed immunity at the ages they would normally have. This meant that when restrictions were lifted, children would be exposed to these viruses all at once, which would overwhelm their immune systems, which are unprepared to deal with them.
However, research will need to be done to find out if this really played a role in the severe hepatitis cases. But if it’s shown to be a cause, we’re likely to see fewer and fewer cases of childhood hepatitis as the months go by since the last. lockdown.
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