Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with [ME/CFS], 2022, Apostolou et al

Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome

Eirini Apostolou, Muhammad Rizwan, Petros Moustardas, Per Sjögren, Bo Christer Bertilson, Björn Bragée, Olli Polo and Anders Rosén.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.

Methods: Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.

Results: At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.

Conclusion: Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.949787/full

 

Nya rön om ME/CFS: Vi presenterar en ny upptäckt om ME!
https://www.bragee.se/nyaronomme

En forsknings krönika: En ny upptäckt om gåtfull trötthet.
https://www.bragee.se/mecell

"The bottom line then is that patients with ME/CFS are more susceptible and have much stronger reactions to a mild covid-19 infection."

"So what are the consequences of this discovery? [Replication needed.]

[...] Now that we suspect new mechanisms, new treatments may also come into question. These could be new antivirals or immune-modifying drugs. It could be developed methods to strengthen the body's resistance, pacing and activity adaptation are given more weight I think. What happens if you supply these nerves, lymph nodes and blood cells with oxygen in excess, i.e. use high-pressure chambers with oxygen therapy? We are also preparing such a study."

 

TV4 Nyhetsmorgon: Banbrytande studie om ME: ”En sjukdom som ska tas på allvar” (8 minuter)
https://www.tv4play.se/program/nyhetsmorgon/banbrytande-studie-om-me-en-sjukdom-som-ska-tas-på-allvar/13796989?offset=1

 

Sounds really significant to a layman like me, hope some more knowledgeable people are willing to shed a light on it.

 

There was no new info in the TV interview (unless I lost it to the fog), other than what has already been posted in this thread. The focus was on tiredness and ME as a "tiredness disease after infection". No mention of PEM.

 

The way the material is presented suggest that the authors do not really understand much immunology I am afraid. Maybe they do but I would be more inclined to take a serious look at the paper if it wasn't presented in terms of pseudoscience.

 

I just noticed that they have updated the title.

The new title is: 'Banbrytande studie förklarar ME och postcovid: ”Vi har tittat på fel vävnader”'

New title (auto-translated):
'Groundbreaking study explains ME and postcovid: "We've been looking at the wrong tissues"'

Old title (auto-translated):
'Groundbreaking study on ME: "A disease to be taken seriously"'

 

So if I understand correctly they found antibodies against herpesviruses to be increased in the saliva (but not so much in the plasma) of ME/CFS patients who had antibodies against sars-cov-2. In ME/CFS patients without increased antibodies against sars-cov-2, there was no marked increase of antibodies against herpesviruses.

Some interesting quotes from the article:

ll the age differences related to anti-viral titers were to be found in participant < 40 years of age, but there was no difference in subgroups in participants > 40 years of age.

The 39 ME/CFS participants with a history of IM as a disease trigger (disease mean duration 13.0 years) were compared with patients without a history. No significant difference was found.

In negative-ME, only VCA IgG was significantly higher compared with the negative-HD.
​

 

This looks promising to me too. But, I don't have advanced science training.

Interesting that saliva was tested. And, the authors say research has been looking at the wrong tissues. Surprising, but also, maybe not, that saliva has not been looked at before. I don't know what would make the difference.

Some pwME can have multiple reactivation of EBV. Maybe this study is onto something.

 

If there are antibodies to latent or asymptomatic viruses found in saliva, would that suggest that some of those reactivated pathogens that are communicable via saliva may now be contagious?

ETA: They mention ME/CFS patients had low functioning NK cells (I think the word they used was "unresponsive"). Pretty cool. Maybe there is diagnostic potential there after all.

 

How about: 'Their dormant virus chews up the energy'

Garbage.

More antibodies does not necessarily mean reactivation.

More antibodies in saliva but not blood suggests better secretion, not immunodeficiency.

It is just the same old simplistic memes trotted out that have been investigated over decades and found not to hold up.

 

That's starting to sound like they just sliced and diced the data until the found something.

 

Looks like this is attracting interest from potential funders...

 

Ref 26 points to one prior saliva study, discussed here:

https://www.s4me.info/threads/saliv...acerda-nacul-cliff-et-al-preprint-2021.18611/

Which makes it strange the current study didn't look at HHV7 as well.

 

https://onlinelibrary.wiley.com/doi/10.1002/ana.26452?af=R

Same old, same old? Don't think so.

 

Synthesis of antibody in salivary gland or higher proportion of IgA might.
Altered salivary composition might produce the effect as an artefact.
It doesn't seem something likely to be important to me.
Even higher antibodies in blood do not mean much.

 

Thanks @Ravn