Doctors are panicking as hundreds of children around the world continue to develop severe hepatitis with no apparent cause. However, the results of two newly published studies have uncovered the suspected culprits of this childhood hepatitis. Both studies attribute genetic factors, COVID-19 containment measures, and at least two viruses that appear to work together to contribute to the increase in hepatitis in children.
In April of this year in Scotland, doctors first noticed a rather strange outbreak of hepatitis in children. Since then, by 8 April, 60 cases of hepatitis in children have been investigated across Scotland, England and Wales, mainly children between the ages of 2 and 5. As of July 8th The World Health Organization (WHO) reported that there were 1,010 suspected cases of acute hepatitis in children in 35 countries.. Antonia Ho, an infectious disease consultant at the University of Glasgow Center for Virus Research (MRC) and who has been investigating the outbreak, said the actual number of children with hepatitis is likely to be much higher than the WHO estimate. One-third of all reported childhood hepatitis cases have occurred in the United States.
This child’s acute hepatitis is usually severe. Globally, 5% of children with hepatitis require a liver transplant and 22 die. What’s more, the cause of this hepatitis outbreak remains somewhat of a mystery. Studies have shown that children with hepatitis usually do not have the virus that causes hepatitis.
Initially, the cause of hepatitis in children was SARS-CoV-2, the causative virus of COVID-19, and adenovirus, a common virus that often causes symptoms similar to colds and flu. Adenovirus had an unusually low rate of transmission during the COVID-19 lockdown, but it appeared to rise sharply as lockdowns were lifted and people started to socialize again.
To find out more, Ho worked in detail with some of the infected children with Emma Thomson, professor of infectious diseases at the same University of Glasgow Center for Virology Research, and colleagues. not yet peer-reviewed recent researchIn the study, researchers compared nine Scottish children with unexplained hepatitis to 58 children without hepatitis.
The researchers studied blood, liver and fecal samples taken from children, as well as samples taken from the throat and nose using cotton swabs. The virus that normally causes hepatitis was not found in children’s samples, but adenovirus was detected in samples of six out of nine children.
The team also discovered another virus called adeno-associated virus or AAV2. Specifically, the virus was found in all nine children with unexplained hepatitis. Children who did not have hepatitis did not have the virus.
It is known that most people are infected with AAV2 by the age of ten, and in general, people begin to develop antibodies to this virus around the age of three. However, according to Thompson, AAV2 has not previously been directly linked to human disease.
A distinctive feature of AAV2 is that it cannot replicate itself and must use another virus. “In this case, we think the adenovirus played the role of a helper virus,” Thompson told reporters at a virtual press briefing on the 25th. It is also possible that the adenoviral infection occurred after the AAV2 infection, or that both viral infections occurred at the same time, she added. “We can’t say for sure at this time which of these viruses caused the hepatitis,” Thompson said.
However, it was not only these two viruses that contributed to the incidence of hepatitis in children of unknown etiology. In genetic testing, the research team found that children with unexplained hepatitis were much more likely to have a gene called ‘DRB1*0401’. 89% of infected children carried the gene, but typically only 16% of the Scottish population. This gene is known to affect the way the immune system works. This gene also helps immune cells decide what to destroy.
released on the 25th of july other studiesIn London, UCL Great Ormond Street Institute of Child Health researcher Sofia Morfopoulou and colleagues performed genetic analysis on samples taken from 28 children. Five of these children received a liver transplant.
“Our findings are in perfect agreement with the findings of the Scottish researchers,” co-author Judy Breuer from the same institute told reporters at a briefing on the same day. Brewer found that in both studies, AAV2 was found in 96% of children with unexplained hepatitis, but only 4% of children without hepatitis.
Interestingly, the team looked for viral genes and evidence that the virus was replicating, but not the virus particles themselves. This could mean that the virus was having an indirect effect on children, or it could mean that it played a role in the children’s immune system and helped with the infection while making them sick.
“We think that AAV2 and human adenovirus may work together to cause childhood hepatitis of unknown origin in children who are initially susceptible to infection due to their immune genes,” says Brewer.
The researchers also suspected that SARS-CoV-2 could also be a cause of hepatitis in children. However, none of the children had symptoms of COVID-19. Some children appeared to have had COVID-19 in the past because they had antibodies to SARS-CoV-2, but their rates of infection were close to those of the entire Scottish population. In addition, the researchers said that the hypothesis that COVID-19 is the cause of hepatitis can be ruled out given that this child’s hepatitis outbreak occurred two years after the outbreak of the pandemic.
However, the COVID-19 pandemic may have played an indirect role in the development of unexplained hepatitis. Measures to reduce social contact, such as lockdown measures, have helped reduce the spread of COVID-19, but have also affected the spread of other infectious diseases. for example Influenza infections and mortality rates have declined sharply in the United States and elsewhere..
The sudden spike in adenovirus infections may be the result of children finally returning to school and hanging out with other friends as before. “As lockdowns are lifted and things are going back to their priorities, many things are coming back,” Ho said.
Thompson emphasized that the riddle has not yet been fully solved. Both studies were done on a small scale, and neither of them have yet been published in a scientific journal. But the results of this study are the clearest picture we have so far. Fortunately, the incidence of unexplained hepatitis in children is declining. Still, the WHO warns that it does not have complete and up-to-date information from all countries.
Researchers believe that similar child hepatitis cases may have been going on for several years, but that this outbreak may have only just come to light because of its spread. “Without the mass infection, the detailed investigation would not have been done,” Brewer said.