Late pandemic immune dysregulation? Opportunistic infections and unexplained pediatric hepatitis

Pyrrhus

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Hip

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Uh-oh. Looks like a post-pandemic surge of enterovirus infections:
I am wondering whether the known long-term immune dysregulation that appears after COVID infection may be the cause of these recent seemingly opportunistic infectious outbreaks. Much of the world has now had COVID, so there may be a lot of people with weakened immunity post-COVID.

Last month we saw how young children were needing liver transplants after a liver infection with adenovirus 41, a virus which normally does not cause much issue.

Then this month, we have seen a global outbreak of monkeypox, and person-to-person transmission of monkeypox (there have been isolated cases of monkeypox in the West before, but never person-to-person transmission, to my knowledge).

Now we see that the incidence of hand, foot and mouth disease from enterovirus has increased 20-fold in Malaysia.
 
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All the scientists who seem worth following on twitter are convinced that this is the case. Many of the ME researchers are convinced as well Hip.

International research has now proved that naive t cells are reduced post infection. T cell exhaustion has also been proven and this appears to occur in more patients than just severely infected. That is they've proven mild patients are also infected.



A new study shows fully vaccinated patients only get 15% protection from long covid. I assume that with all antibodies waning this goes down to zero. Previously lower quality studies had shown 50% protection.



Other immune dysfunctions have absolutely shown up on an almost daily basis over the last 2 months.


https://twitter.com/zalaly/status/1529494840249032705?t=PdyntpAuPI8tFLFyIvbsmg&s=19

As for hand foot and mouth diseeas. My friends baby got this in 2020 sometime around June. He said it was pretty uncomfortable but worse for the baby in terms of symptoms. So this has been going on for ages. Probably unrecorded. I've literally never ever heard of it. Pretty sure I had Coxsackie A as a child too and my parents don't remember.

Anthony j Leonardo has a theory which is that super antigens created by some viruses but always by covid19 are what cause such widespread and systematic damage. People can say this is only a first wave thing but the monkeypox and other viruses sort of beg the question is that really true? I think by the end it the summer we will know.

https://twitter.com/LeonardiBot/status/1529569658654834697?t=d_SM3UYBCUkHdR8S7cx-2w&s=19

https://twitter.com/fitterhappierAJ/status/1305954881497432064?t=P98-qPcj8TYxDXJmlzmTEA&s=19
 

SNT Gatchaman

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Totally agree with the risk of new infections spreading wider and being more pathogenic in a paediatric population almost universally exposed now, many even multiply. I'm worried.

Last month we saw how young children were needing liver transplants after a liver infection with adenovirus 41, a virus which normally does not cause much issue.
As far as I'm aware, there has been no evidence that AdV41 has infected the livers. No biopsy or explant specimens have shown any evidence of viral infection. There have been substantial numbers of cases positive for AdV41 on serology in some countries, but by no means all. I think the informed best working theory is an abnormal T cell response following prior/recent Covid, possibly in association with a subsequent current adenovirus infection (though that may turn out to be co-incidental and irrelevant).

The mechanism needs to be established, because the treatments are polar opposites: antivirals vs steroids. Israel has been successful with steroids. Avoiding transplant should be priority 1. Regrettably, there seems to be a lack of candour around performing and reporting SARS-CoV-2 serology, which has been widely viewed with suspicion.,
 

Hip

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As far as I'm aware, there has been no evidence that AdV41 has infected the livers. No biopsy or explant specimens have shown any evidence of viral infection.
Wow, that seems lazy on behalf of the hospitals dealing with these cases. Livers have been transplanted in several children, so I would have thought it would be easy enough to obtain some liver tissues from the removed liver, and test those tissues for adenovirus using PCR.
 

Hip

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They did in the UK. Zero.
Interesting. So the infectious agent (if any) behind these liver failures remains elusive.

I wonder if anyone has used high-throughput sequencing on liver tissue samples to determine if any pathogen is present in the liver?
 

SNT Gatchaman

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I suspect they won't find an infectious agent in the liver specimens themselves. We see fulminant hepatitis, often requiring transplant, for unestablished reasons regularly, though never in such a surge as has happened recently. Suspect these are probably all variations of immune dysfunction, where the inciting virus has probably "long gone" (at least in terms of meaningful active infection).

Another suggestion has been that this is a variant of MIS-C, which typically happens six weeks post COVID. While multi-system, it's gut-centred and may represent either privileged site viral persistence or perhaps microbiome upset and subsequent uncontrolled inflammation. Liver is next in line from gut via portal blood flow, so potentially a reduction of mucosal integrity could lead to bad proteins/debris reaching gut blood without necessarily causing overt gut symptoms, but then inciting destructive immune cell activity in the liver.

I hope they can do due diligence here as this could answer questions that have eluded us for years. There does seem to be a political reluctance to entertain that this might be due to uncontrolled COVID infection in unprotected children. Many of us have been warning against the "let it rip" policies vocally, but have been overcome by minimising voices speaking bad science to those only too happy to listen. (Dr Gurdasani, as in the above tweets, has been beyond admirable through all of this, facing misogyny and racism, in lieu of valid scientific counter-arguments).
 

Pyrrhus

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I hope they can do due diligence here as this could answer questions that have eluded us for years.
Hear! Hear!

There does seem to be a political reluctance to entertain that this might be due to uncontrolled COVID infection in unprotected children.
Another factor here is the fact that this seems to have occurred suddenly, two years into the epidemic. So why now? What has changed? Is there an immunological depression that allowed normally harmless pathogens to trigger the hepatitis? Or, equally scary, has this been going on all through the epidemic and we are just now realizing it?
 

SNT Gatchaman

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Further follow up on paediatric hepatitis, with latest WHO report. 650 cases, mostly under 5. SARS2 serology available in only 26 (4%), but 73% positivity in those tested. Background positive serology is 47% for UK (one third of cases are in the UK). This is particularly significant given the lower seroconversion / early seroreversion in children.

 

Pyrrhus

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Good article from STAT:

Viruses that were on hiatus during Covid are back — and behaving in unexpected ways

https://www.statnews.com/2022/05/25...vid-are-back-and-behaving-in-unexpected-ways/

For nearly two years, as the Covid pandemic disrupted life around the globe, other infectious diseases were in retreat. Now, as the world rapidly dismantles the measures put in place to slow spread of Covid, the viral and bacterial nuisances that were on hiatus are returning — and behaving in unexpected ways.
 

halcyon

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Another factor here is the fact that this seems to have occurred suddenly, two years into the epidemic. So why now? What has changed?
I think what changed was the public health strategy. Once the vaccines had been out for a few months, everybody switched to “let er rip”, children and the immunodeficient be damned.

I know someone who finally caught COVID in this latest wave. They then caught two further viral infections back to back in the weeks after catching COVID.
 

SNT Gatchaman

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King's College Hospital in London is the largest of three paediatric liver transplant centres in the UK. They have published their findings.

Outbreak of hepatitis in children: clinical course of children with acute liver failure admitted to the intensive care unit (Jun 2022, PDF)

7/8 under 5 years old
(0/8 vaccinated)
6/8 required liver transplant
No evidence of adenovirus in explant or biopsy specimen
8/8 evidence of AdV DNA in blood
8/8 negative for SARS-CoV-2 PCR
6/8 positive for SARS-CoV-2 serology (1 negative, 1 indeterminate)

The 75% SARS seroprevalence is a strong signal of implication, given the population child prevalence rate (1-4 years old) was 47% at the time.

Also note AdV DNA persists in blood for variable time.

However, histopathology studies on the explant liver and in a few who have had biopsies have not demon- strated evidence of adenovirus in hepatocytes, though all of them revealed hepatocyte necrosis and parenchymal collapse. The lack of adenovirus demonstration in hepatocytes, but severe liver injury leading to acute liver failure may be related to an aberrant immune response from the host’s immune system of liver.
Detailed characterisation of immune infiltrates in the liver of children who progress to liver failure may identify a subgroup that respond to immunosuppression including steroids and avoid liver transplantation. Media speculations relating this outbreak to SARS-CoV-2 or vaccine are not yet substantiated. The presence of adenovirus in these children raises a hypothesis of SARS-CoV-2 superantigen mediated disease potentiated by a second virus. The hypothesis of an aberrant immune response in those (<10%) who required urgent transplantation is being investigated.
The most important point was that treating these children as "adenovirus hepatitis" leads to a very high rate of transplantation. Treating as an aberrant immune response, with steroids, can lead to salvage with no requirement for transplant.
 

SNT Gatchaman

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I would put more weight on the sheer numbers of children infected, following the "let it rip" policies. Previously the children were much more protected from infection. This is a rare outcome but we're probably seeing more now because of the denominator.