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Are Rising Hepatitis Cases in Kids Linked to Covid?

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(This column was co-authored by Sam Fazeli)

Over the past month, the UK, U.S. and other countries have reported increasing cases of acute hepatitis, or inflammation of the liver, in otherwise healthy children, some as young as one month old. Some have required liver transplants and at least one death has been reported. 

The reports first emerged in Scotland in early April and then across the UK. There are at least 165 cases across a dozen countries, including the U.S., Denmark, Spain and the Netherlands. The Centers for Disease Control and Prevention has issued an advisory warning about the outbreak, and the World Health Organization has also released statements.

I spoke with Bloomberg Intelligence pharmaceutical senior analyst Sam Fazeli about the cases and how they might be connected to SARS-CoV-2. 

Therese Raphael: Can we start with what constitutes a significant outbreak? The aggregate numbers seem quite low. Indeed, the WHO had said it wasn’t clear if there were really more cases of acute hepatitis or just more awareness given that often hepatitis goes undiscovered. How do we know if this is significant?

Sam Fazeli: The WHO’s comment is absolutely right. There is heightened awareness of infectious diseases. We have become much better at testing for infectious agents because of the pandemic and so it’s very possible that this is the case with the hepatitis numbers.

TR: We are normally used to seeing a letter after hepatitis — A, B, C and so on. But here they didn’t find any of the usual suspects. Does that suggest an entirely new virus is at work?

SF: Those letters all relate to the type of virus that causes the hepatitis, ranging from A to E. They all transmit in slightly different ways and can remain dormant for most of the life of an infected person. There are vaccines for some (for example, Hepatitis B) and very good drug therapies for others (Hep. C). The problem with the latest childhood cases is that there is no trace of these usual viruses, raising the need to look for another causative agent.

TR: One possible explanation put forth for the outbreak is that it has been triggered by an adenovirus, which is responsible for common colds among other illnesses. It was identified in cases in the UK., and Alabama’s public health authority reported nine cases in young children in April, all with something called Adenovirus 41. Would an adenovirus be a trigger here and what are the implications if that’s so?

SF: Well this is a very large family of viruses, of which there are 88 known to infect humans (human adenovirus is written HAdv) and can cause a variety of diseases. They are divided into groups from A to G (this has nothing to do with the classification of hepatitis viruses). Adenovirus family F contains 40 and 41, both of which are very rare. Respiratory disease is caused by the B and C families, whereas 40F, 41F and 52G cause gastroenteritis. D is known to cause conjunctivitis.

If indeed HAdV-41F is the causative agent for these hepatitis cases, not only would it help us increase surveillance but we can also try to develop a vaccine.

But there is no certainty yet that this is the case. The UK has reported the highest number of cases (163 as of May 3) with adenovirus detected in 91 of 126 samples tested. Now this does sound like a lot, but bear in mind that the majority of children are infected with some adenovirus at any one time. The incidence of HAdV infection peaks between six months and five years of age. By five, 70% to 80% of children have  neutralizing antibodies for one of the adenoviruses.

But detailed genomic analysis of 18 of the UK cases has shown 100% were 41F. So it is possible that this virus, which is thought to be present in 5.3% of cases of gastroenteritis in the U.S. according to one study, is the cause of the hepatitis cases currently seen across the globe.

TR: Another hypothesis raised by Scottish investigators was that the hepatitis cases could be the result of “immunologically naive” children. How would that work? 

SF: It is possible that two years of reduced infection rates for a whole variety of viral diseases has led to children not having encountered an adenovirus. This could then work in two ways. One possibility is that infection by a related adenovirus provides some protection against severe disease caused by another, in this case 41F. And, given that during the pandemic lockdowns most infections were suppressed, this cross-protection is no longer in play for some. Another possibility is we are now seeing a concentration of catch-up infections.

TR: If that’s the case, would we expect to see the curve taper off over time as kids get used to normal interactions? 

SF: There is some evidence this is happening in the UK but it’s too soon to know.

TR: Some of the children with acute hepatitis had Covid and some presented with both Covid and an adenovirus. Are there other ways this could be related to SARS-CoV-2? 

SF: Sure. An infection by one virus can lead to activation of another virus, such as Epstein Barr virus or a herpes simplex virus (the kind that causes cold sores). It is also possible that a SARS-CoV-2 infection changes the body’s response profile to another infection, in this case an adenovirus. But all of this needs data before it can be established. If a link is proven, even in some cases, then it provides yet another reason to vaccinate those under the age of five with a SARS-CoV-2 vaccine, assuming the risk-benefit argument works in favor of vaccination.

More From Bloomberg Opinion:

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• McDonald’s Exit From Russia Ends a Hopeful Era: Therese Raphael

• Zoonotic Spillover Is the Apocalypse You’ll Be Hearing About a Lot: Andreas Kluth

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Therese Raphael is a columnist for Bloomberg Opinion covering health care and British politics. Previously, she was editorial page editor of the Wall Street Journal Europe.

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