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

mango

mango

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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
Auto-translate said:
A research team at Linköping University, in collaboration with us at the Bragée ME center, has published an article in the prestigious journal Frontiers in Immunology today, 20 October 2022, describing a new mechanism that may shed new light on both ME/CFS and PostCovid.

You can read my chronicle of the research project here.
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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."

Auto-translate said:
A research chronicle: A new discovery about mysterious tiredness.

Why can't anyone find the virus behind ME/CFS? Because, truth be told, many have searched over the years, but never found evidence of any new virus or any particular guilty infection. In fact, those of us who have worked with the disease have seen how many patients seem to get their unexplained knockout after all sorts of flu-like conditions. Even quite a few without even describing any apparent infection. Professor Anders Rosén at the University of Linköping Biomedical Institute has described advanced findings in ME for many years and in several articles, but still asked himself the same question. When the pandemic hit like an unexpected bomb, amidst all the misery and darkness, there was also an opportunity.

The undersigned warned already in the spring of 2020, in an article in Dagens Medicin, that Covid19 could drastically increase the risk of ME. After all, the history of ME was lined with various viral outbreaks and their consequences, and in the wake of the last SARS pandemic, Norway saw a doubling of the number of people diagnosed with ME. Would this be the case, and how would all our patients with ME react to this new viral infection that they were at risk of contracting?

So when Professor Rosén and his research team got in touch and asked if we at Bragée Clinics, who have so many carefully diagnosed patients, would like to help in a research study by taking samples from patients for a year and following what happens, it seemed obvious to contact interested patients. And a lot of people wanted to volunteer. We ended up with 95 ME patients and Linköping contributed 100 healthy people to compare with. And the findings would prove to be very interesting.

We might not find any new virus when we search around in ME/CFS. This is because it is old infections that we have had in the past that are haunting us! Viruses that have been dormant in the body's cells and come back to life when we get new infections of various kinds, for example during a pandemic!

It is well known, for example, that viruses of the herpes family can lie dormant for decades in the body and then be awakened by stress or infection, causing tiredness and fever, and not infrequently aches and pains, which are then called latent. We even have congenital viruses like "retrovirus-K" that can bloom in the same way and cause both malaise and sometimes autoimmune diseases like rheumatic joint pain, but most of all tiredness. Symptoms not unlike those reported by both ME and PostCovid patients, i.e. prolonged fatigue after Covid19.

So today on TV4's News Morning I had the opportunity to talk about the research team's new discovery. It was real news as the scientific paper was published internationally at the exact same time, so TV4 was on the ball. Lead authors Eirini Apoustolu and Anders Rosén are, like their colleagues, super-experts on viruses and the immune system, and our paper has now been published in the prestigious journal Frontiers In Immunology. Such an article is not so easy to read, so to speak. After all, the title alone can be a bit of a challenge "Saliva Antibody-Fingerprint of Reactivated Latent Viruses after Mild/Asymptomatic COVID-19 is Unique in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"

so I thought I'd explain it a bit simply, without losing too much in scientific accuracy.

Professor Anders Rosén's team in Linköping, led by Eirini Apostolou, has advanced equipment and world-class expertise in analysing antibodies and the immune system. After a year of driving the chilled samples down to Linköping every week, this summer they could be brought out of the freezer at more than 80 degrees [Celsius] below zero and analysed simultaneously. Exciting times - would we see any difference between "our" patients and the healthy patients, the so-called controls? The lab team first concentrated on how many had received Covid-19 during the year, and it was more than half of the ME patients, and a little less among the controls. And the symptoms had been mild, with a third not even noticing they were affected by the pandemic. It only showed up in blood tests. We had just as much difficulty determining who had Covid-19 when we met the patients for testing, as ME/CFS is a disease that itself varies greatly depending on the efforts you make. I can't believe there were so many!

So what about the dormant viruses that are found mainly in white blood cells and nerve cells? Had they been awakened, or reactivated, as it were, by Covid-19? Such awakenings tend to produce less severe infections and more diffuse symptoms such as fatigue, fever or exhaustion. It is also well known that the body's energy powerhouse in the cells, our mitochondria, are hijacked by infections. Yes, stress and strain too. Now, if the pandemic had knocked out our internal power plants, it's no wonder that many people would experience extreme tiredness and deterioration...

Yes, both patients and controls had activations of various herpes viruses and the congenital retrovirus-K, but the response was much stronger in those with ME/CFS. They had a significantly, i.e. statistically certain different test response, especially from the core virus EBNA1, i.e. from the Epstein Barr Virus or EBV. And then only in saliva, not in blood samples. It was not entirely unexpected that EBV was a culprit in the drama. Almost all individuals have antibodies because they were infected with EBV early in childhood. Some are infected later in adolescence and then develop a splendid infection with general swelling of the lymph nodes, glandular fever, or as it is also called "kissing disease", as it is transmitted through mucous membranes. After these infections, EBV slumbers in our lymphocyte blood cells and waits patiently to be awakened. And apparently the new pandemic virus was such a wake-up call. The fact that we didn't understand this before may be partly because we normally take blood samples and not the simpler saliva samples that we also did in our study.

The bottom line then is that patients with ME/CFS are more susceptible and have much stronger reactions to a mild covid-19 infection. Their dormant virus is awakened and chews up the energy and the result is more tiredness, more exhaustion and a feeling of fever, rather than typical flu symptoms. And this is probably how it can be with many different flu infections, patients with ME often report how they get "minor infections" and exacerbations time and time again. Again and again, the power plants shut down. And you get worse general health and a weaker immune system. Not only have you been infected with a new virus, you have also awakened an army of dormant former sinners who are reactivated.

So what are the consequences of this discovery? Well, first of all, several research groups will have to get involved to see if we/our research group are right or wrong! And we ourselves have many new studies in the pipeline, but perhaps most importantly, it is very difficult to find a cure and a cure for a disease that is not understood. 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. Yes, there are many ideas.

Perhaps this will give some hope. And the knowledge that "it's not just psychological" but that testing and advanced analyses actually also show clear differences is not only a comfort, but also an inspiration for the health care system as well as for the patients and their relatives.

I would like to thank the team at Linköping University, all our staff and, above all, our committed patients!

Björn Bragée, pain physician, co-author

Here you can read the article, there are also nice maps of virus types and test results.

REF

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

Frontiers in Immunology, 20 October 2022.

Related links

External links
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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
Auto-translate said:
Groundbreaking study on ME: "A disease to be taken seriously", 8 min
Previously it was thought that the enormous tiredness felt by many ME and post covid patients was due to a virus. Now, a new study has finally brought us one step closer to an explanation. Pain doctor Björn Bragée joins us to teach us about this exciting new research. Bragée says the new research may also give legitimacy to patients who have struggled to get recognition of the condition.
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mango said:
TV4 Nyhetsmorgon: Banbrytande studie om ME: ”En sjukdom som ska tas på allvar” (8 minutes)
https://www.tv4play.se/program/nyhetsmorgon/banbrytande-studie-om-me-en-sjukdom-som-ska-tas-på-allvar/13796989?offset=1
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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.
Auto-translate said:
Bragée: This is not a psychiatric illness. This is not laziness. This is not a question of avoidance behaviour. This is a biological, ascertainable, serious disease that should be treated as such by the health care system and the Social Insurance Agency, relatives and the community.

Presenter: That is important to point out. It is a shame, and must be taken seriously.

Bragée: Yes, and now that we can even see significant differences in something as simple as a saliva test, you understand that this causes quite significant changes in the body. [...]

The next step for us is to start looking at the genome, so DNA, heredity and things like that. And start different types of treatment studies, of course. [...]

And those things we keep saying, take it easy, don't exercise but take it step by step, baby steps, do pacing, learn to manage your activity.
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mango said:
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
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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.
 
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Trish said:
Can you explain which parts are pseudoscience?
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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.
 
ME/CFS Skeptic said:
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.
​
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That's starting to sound like they just sliced and diced the data until the found something.
 
I understand that the antibodies titles can be meaningless per se.

My question was more about the repartition of the antibodies. Why would there be a difference between patients and control? If you can separate a population in two groups with a blood test and that it matches repartition of the patient group and control group, can't that mean anything or could it be just chance or methodolical flaws?
 
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