Why do some viruses take months to recover from, and does that tell us anything about ME/CFS?

For most people, a cold lasts a few days but glandular fever can last many months. What drives the difference? Is it viral persistence, or something else? And does that tell us anything about postviral ME/CFS?

 

If viruses are simply a trigger for the ME state (for some people), then it probably doesn't tell anything about ME itself, especially if it can also be triggered by non-viral events.

 

What is it, though? Do viruses such as EBV fire up a bit of the immune system that can take ages to shut down, but eventually do so?

 

We have had discussions before about whether some viruses are more likely to be associated with ME onset than others, but not really reached any firm conclusions. Is there any link between the viruses that take longer to clear and those that seem to be associated with triggering ME, such as EBV?

Also there is the idea that some viruses are more likely to trigger reactivation of other viruses dormant in the system than others. Could it be combinations of different viruses that is the issue?

 

If I exerted a similar amount of energy as my body did fighting a virus doing something else, ie. getting a surgical procedure, overexerting for long periods, it will also take months to recover from or I may never recover.

I therefore don’t think viruses are important to this phenomenon, it seems to be something common with all types of major overexertions in pwME.

 

I find this question really intriguing, irrespective of it's relevance to ME (or long COVID). I don't have the relevant background to do more than speculate, but somebody here must have some idea, surely?

 

@Sasha I just realised my comment is completely irrelevant to your post, you asked about why some viruses take months to recover from in general, and I answered why some viruses take months to recover from for pwME. My bad!

 

No problem, don't worry!

 

I can think was discussed somewhere else already and there was a possible explanation. Maybe in the needing to lie down thread?

Edit: Found the reference:

 

2 viruses might be hard to detect. One might remain undetected

This, and or other opportunistic, or co-morbid, infections, might or might not, help to explain:

- loss in resistance, resilience, recovery & repair
- protractions and protracted aftermaths
- various inflammatory markers

Eg pre-covid, some unususal things remained unexplained, as too hardly explained.

But after covid then became explained, eventually, by hard work, while experts on national TV told us all: the technology exists to test for all viruses etc etc but it is still not being used

After covid, intensive investigation of unexplained, lethal, paediatric hepatitis, found the (EDIT: suspected) atypical co-morbid adenovirus

So 2 viruses may inflame a liver where 1 virus may not

And also may protract recovery, maybe

- if susceptible for some reason

A likely cause:

The two teams of researchers, from London and Glasgow, say infants exposed later than normal - because of Covid restrictions - missed out on some early immunity to:

• adenovirus, which normally causes colds and stomach upsets
  
  
• adeno-associated virus two, which normally causes no illness and requires a coinfecting "helper" virus - such as adenovirus - to replicate
  

.

 

.
For example, the "helpers" of the "helped" virus: adenovirus 2

This is a collection of loosely associated info, and some speculation, which might signify, or I might be up the creek without a paddle. The research cited might have been followed up since

I don't know if the DECODE indications of liver involvement might correlate to other liver involvements found, and to the lingering of viral infections (complicating and compounding)

- as in this post: liver cases co-morbid with covid

- and as in above post: liver cases with no significant covid connection. But those case-studies mentioned genetic susceptibility, and lockdown lacks of exposure, and seasonal coincidences; with top suspect being the adenovirus 2 (and "helpers"):

"AAV2 does not typically cause illness itself and needs a ‘helper’ virus to be able to divide in the body"

These attacks on the liver seem to LINGER

4th Technical briefing on AAV2 and other suspects

Spoiler: alleles and stuff

...associated with the presence of adenovirus infection and both researcher groups also detected AAV2 infection as well asindications of a potential immunological component.

AAV2 may be an indicator of a recent adenovirus (or other) infection but given the strong association further investigations are merited...

... Analysis of HLA allele positivity in 9 early Scottish cases indicates that 8 out of 9 cases (88.9%) carried the HLA-DRB1*04:01 allele. In comparison, the frequency of HLA-DRB1*04:01 in a control Scottish population (n=974) is 8.9%...

... SARS-CoV-2 was not detected by PCR and sequencing in any clinical samples, including liver samples, in cases or controls. Six of 9 (67%) of the case patients had SARS-CoV-2 spike (S)

or nucleocapsid (N) IgG antibodies,

which is comparable to SARS-CoV-2 seroprevalence in children in Scotland during the study period (59 to 67%)

AAV2 typically needs a co-infecting ‘helper’ virus to replication, most commonly adenovirus or a herpesvirus.

Adenovirus (C or F) were found 6 out of 9 case samples, include 3 out of 4 liver biopsies, while human herpesvirus 6B (HHV6B) was detected in 2 out of 9 case samples, including 2 out of 4 liver biopsies.

A full genome of adenovirus F41 was retrieved from a faecal sample and was found to be closest to 2 genomes reported from Germany in 2019 and 2...

... Most of the cases had presented with a subacute history of gastrointestinal symptoms up to 11 weeks prior to onset of acute hepatitis.

Using metagenomic and target enrichment sequencing and real-time PCR, AAV2 was identified in

- plasma of 9 out of 9 and
- liver of 4 out of 4 cases but in

- 0 out of 13 of sera/plasma of age-matched healthy controls

- 0 out of 12 children with adenovirus infection without hepatitis and normal liver function and

- 0 out of 33 children admitted with hepatitis of other aetiology...

Near full genomes of AAV2 were detected in all 9 cases...

... GOSH also report that assessment by electron microscopy, immunohistochemistry or proteomics could not find AdV or AAV2 viral particles or proteins in explanted livers, suggesting that

hepatic pathology is not due to direct lytic infection by either virus....

... Analysis of the 5 transplanted cases in the GOSH series carried out under International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) consent, found at least one of these alleles to be present in each of the 5 cases, with HLA DRB1*0401 being present in 4 out of 5.

Whole genomes were not obtained from the blood of any case due to high Ct values. However, GOSH report that partial sequences were identified as AdV-F41 with reads positioned across the entire viral genome and were not suggestive of a recombinant virus

... The data shows an association of Adeno-associated virus 2 (AAV2) at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent Adenovirus F41 (AdV-F41) outbreak

Lesser suspects were

- Adenovirus (AdV)
- Human Herpesvirus 6B (HHV-6B)

"Both of which enable AAV2 lytic replication"

Spoiler: These non-Covid studies used metagenomics

The studies used metagenomics, studying samples taken from those affected, to take an unbiased approach to seeking other viruses that may be involved in the cause of the outbreak

In addition to supporting the finding on adenovirus, both studies detected adenovirus associated virus 2 (AAV2) in the majority of cases studied, but absent (or at low levels) in samples taken from people unaffected by the outbreak as part of the study (known as controls)

AAV2 does not typically cause illness itself and needs a ‘helper’ virus to be able to divide in the body

There are also some early findings which suggest that differences in people’s immune systems could potentially be playing a role.

At the moment, it is too early to say how these findings interact and which ones are significant in context of the outbreak.

There may also be other "helper / helped" viruses, likewise not typically tested for

It seems a "helped" adenovirus 2 can somehow prolong, and so exacerbate an apparent inflammation

Maybe, at first, its a systemic inflammation, then it hit the susceptible cases in the liver, badly enough, across the world, in enough cases, to be revealed, maybe. But it might hit elsewhere

I am not sure, so I guessed that, retaining a "synthetic" liver function (in the non-covid cases), means the damage, assumed as indicated by the raised enzymes, is not typical, and so no local pain, not yellow, no nausea

I gather some research showed: that raised enzymes can indicate damage elsewhere. It might not be in the liver. It might be in the skeletal or heart muscle, the kidney, the brain, or the erythrocytes (might even explain a high ESR)

Its all very intriguing:

The other aminotransferase synthesis sites

The ALT tested, in great detail

=======================

In the Covid-connected cases, the liver can also take a hit, but these cases seem to be non-symptomatic Covid, otherwise

Sometimes showing a treatable "complement hyperactivation", whatever that is.

These attacks on the liver can also be lethal and/or severe, as also ?LINGERING?

What Is Known/What Is New

What Is Known

• Coronavirus disease 2019 (COVID-19) can cause elevated liver enzymes in children.
  
  
• Severe hepatitis in COVID-19 is typically associated with significant respiratory or systemic symptoms.

What Is New

• COVID-19 in the absence of significant respiratory or other symptoms may be associated with pediatric acute severe hepatitis and even acute liver failure.
  
  
• Complement hyperactivation can be associated with hepatic dysfunction in COVID-19 and may improve with targeted therapy

"None of the patients had respiratory symptoms. One patient was found to have complement dysfunction resulting in microangiopathic features and was treated successfully with eculizumab.

"This case is in line with adult post-mortem data showing that more severe cases of hepatic dysfunction secondary to COVID-19 infection may be associated with complement activation and microangiopathic features

"Liver function should be evaluated in cases of severe COVID-19, and severe acute respiratory syndrome coronavirus 2 infection should be considered as a cause of acute severe hepatitis

even in patients without significant respiratory or other systemic symptoms" !!!

I guess such things can also happen without a Covid

To a GP, a "slight liver infection" might not be worth mentioning or investigating for the patient record. Its not that surprising if a liver involvement, genetically indicated, might have escaped the NHS notice, for 70 yrs, or maybe even got forgotten 50 years ago

Even if lingering
.

 

I find this interesting going back to my experience of vaccines, no problem with the flu one but significant issues with mRNA and viral vector covid-19 ones. So my body is, for some reason, reacting very differently to I guess the spike proteins?
So within the wider population why not differences in how the body (or some people’s bodies) responds to both severity but also type of virus? No idea if this has a relationship with ME/CFS, just as likely not. But how and how long the body responds to things is vey interesting and I’m assuming given the complexity of the immune system and many different virus.. complicated.

 

@mariovitali

 

I thought that was such an interesting question that I've just started a whole new thread on it!

 

Most persistent infections do so because they mess with the immune system.

We know the severity of SARS-2 was primarily due to avoiding the immune system (it was the exact opposite to "cytokine storms" - that is also why it affected older people more), namely suppressing type I interferon responses and syncytial infection in the lungs.

EBV has 85+ open reading frames, many of which code for genes which are there to mess with/evade the immune system
https://www.ncbi.nlm.nih.gov/books/NBK304353/

The longevity of the infection is generally associated with increased risk of ME/CFS (or LongCOVID), but this is not the same thing as viral persistence being the cause of those conditions.

Another hypothetical factor is the fact that virtually all infections associated with ME/CFS are neurotropic.