Researchers and health officials are vying to determine the cause of an unexplained outbreak of pediatric hepatitis, as more cases are reported worldwide each day. Unfortunately, the mysterious pile of cases is also causing a burst of misinformation.
“People are speculating as they turn blue, but all we have is a bunch of correlations and there is no definite reason,” Isaac Bogoch, MD, of the University of Toronto, told the Financial Times.
As previously reported, a group of cases of pediatric hepatitis was first discovered two weeks ago in the United Kingdom. At that time, 60 cases in England and 13 cases in Scotland were investigated, mostly among children aged 2 to 5. Shortly afterwards, nine cases dating back to last fall were reported in Alabama.
Once health professionals knew what to look for, new messages began to flood in. The unexplained disease has already been detected in more than a dozen countries, including Canada, Japan, Israel and several European countries. Nearly 200 children were affected, ranging from 1 month to 16 years, although most were preschoolers. At least 17 children needed a liver transplant and at least one died, according to a World Health Organization newsletter that is no longer up to a week old.
CDC National Health Signal: A group of children identified with # hepatitis and # adenovirus infection. Physicians should be alert to symptoms and report all suspected cases of hepatitis of unknown origin to their local and state health departments.
– CDC (@CDCgov) April 21, 2022
In the United States, the Centers for Disease Control and Prevention (CDC) issued a national health alert on April 21, asking doctors to be vigilant about possible cases. So far, more than two dozen cases have been reported in the states, including Alabama, California, Delaware, Illinois, New York, North Carolina and Wisconsin.
What is causing the epidemic? Hepatitis simply means inflammation of the liver and can have many causes. Viral hepatitis (including hepatitis A, hepatitis B and hepatitis C) is the best known. The condition can also be caused by fatty liver disease, heavy alcohol consumption, toxins and some inherited conditions.
Signs and symptoms of hepatitis – regardless of the cause – include elevated liver enzymes, jaundice (yellowing of the skin and eyes), dark urine and pale stools. It can also cause less specific symptoms, such as fatigue, fever, loss of appetite, abdominal pain, nausea and vomiting.
Although the cause of the outbreak of pediatric hepatitis remains unknown, many suspects are under investigation. Press reports and social media discussions have suggested that this may be a complication of COVID-19 or the result of blocking COVID, but neither has been confirmed by the available evidence.
Several leading hypotheses were described during an emergency session of the recent conference of the European Society of Clinical Microbiology and Infectious Diseases in Lisbon and presented at a briefing by the UK Health Security Agency.
There are so many uncertainties. Working hypotheses include: – co-infection of adenovirus with other infections – factors that increase the susceptibility and severity of adenovirus infection – toxins, drugs or environmental factors There is still work to be done # ECCMID2022 pic.twitter.com/byDbWYZNIk
– Muge Cevik (@mugecevik) April 25, 2022
First, some reasons can be ruled out:
- Affected children were negative for well-known hepatitis viruses (A, B, C, D and E).
- Few, if any, of the affected children have been vaccinated against COVID-19, as children of this age still do not qualify in most countries.
- Most of the children are over 2 years old, which means that their mothers would not be pregnant during the COVID pandemic.
- Adenoviruses used as vectors in some COVID vaccines (adenovirus type 26 in the J&J vaccine and chimpanzee adenovirus in the AstraZeneca-Oxford vaccine) were inactivated and did not cause disease.
- So far, no shared exposure to potential toxins, contaminated food, drugs or other environmental factors has been identified.
The leading suspect is adenovirus type 41, according to most health experts investigating the outbreak. More than 50 types of adenovirus can cause infection in humans. Although these viruses are best known to cause the common cold, this particular type is associated with gastrointestinal diseases.
Most of the affected children had detectable adenovirus in their blood, and type 41 is the most common among those with available molecular sequencing results. However, in Alabama cases, adenovirus was not detected in liver biopsy specimens.
Adenoviruses are widespread and the infection is common in children and adults. This raises the question of why they have not previously been associated with outbreaks of liver disease. There have been previous reports of adenoviruses causing hepatitis, especially in immunocompromised people, but this seems to be rare.
It is possible that a new or previously unrecognized adenoviral strain is the culprit or that the adenovirus interacts with another pathogen to cause a more severe disease.
Some experts, including the authors of a Eurosurveillance report on the Scottish case, suggest that reduced microbial exposure due to “limited social mixing” during the COVID-19 pandemic may have left children with inadequate immunity. But this raises the question of why cases occur in areas with and without blockage and at different intervals after the end of COVID restrictions.
How about COVID?
The emergence of an unexplained outbreak of pediatric hepatitis during a global pandemic has led many to wonder if SARS-CoV-2, the coronavirus that causes COVID-19, is to blame.
“Whatever theory you join, it has to come from the huge public health event of the last two years,” Alistair Sutcliffe, a professor of general pediatrics at University College London, told the Financial Times. “It’s too much of a coincidence – it’s either a drop in immunity to adenovirus, or the adenovirus is collaborating with COVID to cause hepatitis, but the pandemic has to play a role.
SARS-COV-2 was found in only a small proportion of children involved in the epidemic. But the virus usually clears up after a few weeks, and the lack of viral material at the moment does not mean that the child has not had COVID in the past. In fact, the growing prevalence of COVID – a recent CDC study found that 75% of children in the United States have SARS-CoV-2 antibodies – suggests that many of these children may have been infected. Researchers are now reviewing medical records, testing for antibodies and analyzing liver biopsy samples in an attempt to learn more.
SARS-CoV-2 is not just a respiratory virus and it is becoming increasingly clear that it can damage organs throughout the body. Potential COVID-related liver disease has been reported in adults and children during the pandemic.
In August 2020, for example, researchers in New York reported that 19 of 44 pediatric patients with COVID-related multisystemic inflammatory syndrome in children (MIS-C) had inflammation of the liver. Another U.S. team recently reported four healthy children who presented with severe hepatitis as a major manifestation of COVID-19. And in India, researchers reported 37 cases of what they called “COVID-19-related hepatitis in children” during the country’s second wave, 10 of which were severe.
This raises even more questions. Given that the pandemic is in its third year, why will the outbreak of hepatitis in children only appear now? This may be due in part to the fact that clinicians and healthcare professionals are now looking for it, and the sporadic cases seen in the last two years may in fact be the same.
Perhaps SARS-CoV-2 interacts with adenovirus (several affected children have tested positive for both coronavirus and adenovirus type 41). Maybe there’s something unique about the omicron version that makes it more likely to cause liver disease in children – or maybe the culprit is a new, unrecognized version of SARS-CoV-2. Perhaps COVID triggers immune dysfunction, which leaves children less able to repel other viruses or keep them under control.
Important information for parents about hepatitis in children ????????
Please note: if your child shows signs of jaundice (yellowing of the eyes / skin), see a doctor immediately!
Dr. Jerome Adams talks about a mysterious disease affecting children’s livers – WISH-TV
– Jerome Adams (@JeromeAdamsMD) April 27, 2022
Good science takes time and experts emphasize that it is extremely important to study all possible causes and not to jump to conclusions. While this investigation is ongoing, health officials are urging parents to be vigilant about the symptoms of hepatitis and asking clinicians to report suspicious cases to their local or national health authorities.
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