Trial Report A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome, 2023, Briese et al.

SNT Gatchaman

SNT Gatchaman

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A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome
Thomas Briese; Rafal Tokarz; Lucinda Bateman; Xiaoyu Che; Cheng Guo; Komal Jain; Vishal Kapoor; Susan Levine; Mady Hornig; Alexandra Oleynik; Phenix-Lan Quan; Wai H. Wong; Brent L. Williams; Suzanne D. Vernon; Nancy G. Klimas; Daniel L. Peterson; Jose G. Montoya; Walter Ian Lipkin

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%–2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high‐throughput sequencing. We found no consistent group‐specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.

Link | PDF (Journal of Medical Virology, paywall)
 
Our analyses included plasma, peripheral blood mononuclear cells (PBMC), stool, and saliva from ME/CFS cases and healthy controls, representing two separate case‐control cohorts.
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Cohort 1 samples included plasma from 285 ME/CFS cases and 201 healthy control [...] ME/ CFS cases were enrolled, if they met the 1994 Centers for Disease Control and Prevention (CDC) CFS case definition and had not received antibiotics within the 3‐month period before enrollment. Potential control subjects were excluded if they had received antibiotics within a 1‐month period before enrollment.
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Cohort 2 samples included PBMC, feces, and saliva samples collected under the auspices of the NIH Center for Solutions for ME/CFS. The study included 106 ME/CFS cases who met both the 1994 CDC and the 2003 Canadian Consensus criteria for ME/CFS and 91 healthy control individuals.
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The richest virome was identified in saliva. Findings were dominated by herpes‐ and papillomaviruses. [...] HHV‐6 and HHV‐7 were encountered together most frequently in cases and controls (65% and 74%, respectively). [...] No significant differences in the prevalence of viral sequences were found between cases and controls.
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Samples from the subjects reported here were collected before the COVID‐19 pandemic; thus, our findings may or may not have implications for understanding the pathogenesis of Long COVID/postacute sequelae of COVID‐19.
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all ME/CFS subjects were symptomatic at the time of sample collection. Thus, if symptoms were linked to an active herpesvirus infection, our inability to detect viral nucleic acid was due to replication in a site other than PBMC and that did not result in shedding into blood, saliva, or feces. Our inability to detect direct evidence of an association between viral infection and ME/CFS does not exclude a role for viral infection in its pathogenesis. It does, however, suggest that rigorous exploration of this hypothesis will require serological methods that can retrospectively detect exposure in instances where the infection has cleared and viral gene products are no longer detectable in accessible samples such as blood, saliva, or feces.
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Which is why non-invasive strategies, such as [18 F]F-AraG-labelled activated T cell PET imaging, could be really helpful. They can guide focus to biopsy-accessible tissue reservoirs (eg gut) or at least indicate troubled but biopsy-inaccessible regions (eg CNS). See —

Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to Two Years Following COVID-19 (2023)

and for background on [18 F]F-AraG —

Biodistribution of a Mitochondrial Metabolic Tracer, 18FF-AraG, in Healthy Volunteers (2022, Molecular imaging)
Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy (2019, Cancer Research)
 
It does make me question the value of ME/CFS patients getting tested for viruses with blood samples in labs like Armin labs. [like I do with their tick-borne infection testing],
 
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When someone says not to test for viruses or bacteria or parasites, it makes me want to test for those all the more - especially in tissue, which someone once said not to bother testing.

I wonder how many patients were in this cohort, and what their demographics were.

Did they only test for viruses? No bacteria or parasites or mold?

And btw, cool list of authors - like a Who's Who of US ME/CFS researchers/clinicians.

I have to add that it seems to me highly improbable that NO ME/CFS patients will have active persistent infections, even if immune dysregulation proves to be the main culprit. I have to believe it's just a question of how large a portion can eventually demonstrate those persistent infections.
 
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Amw66 said:
Tissue.
Most arguments re viral persistence are that it's tissue that provides the reservoir.
Some COVID research has turned up viral evidence in tissues I believe.

Not so easy to look at .
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Is this is the study you are referring to? to https://www.medrxiv.org/content/10.1101/2023.07.27.23293177v1.full.pdf+html

From the abstract :

We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID.
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Amw66 said:
Tissue.
Most arguments re viral persistence are that it's tissue that provides the reservoir.
Some COVID research has turned up viral evidence in tissues I believe.
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Tissue was not tested but I wonder if a virus was there if it would not leave traces in the blood and elsewhere. As somebody noted: "The question is what these viruses can do while replicating at such a low frequency that they are not detected in the blood.
 
ME/CFS Skeptic said:
Tissue was not tested but I wonder if a virus was there if it would not leave traces in the blood and elsewhere.
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I know some viruses have a tropism for tissue, e.g. influenza A toward the lungs, but I'm not sure about traces that serology would detect. I do know, however, that some bacteria are tissue-tropic and traces are next to impossible to find in the blood and waste. PCR is hit or miss. Antibody responses may or may not be there. Etc. etc. That doesn't mean the bacteria aren't causing disease in some area like the brain. Shy of a biopsy, however, or if fortunate, a CSF hit, the patient might never know.
 
duncan said:
I know some viruses have a tropism for tissue, e.g. influenza A toward the lungs, but I'm not sure about traces that serology would detect. I do know, however, that some bacteria are tissue-tropic and traces are next to impossible to find in the blood and waste. PCR is hit or miss. Antibody responses may or may not be there. Etc. etc. That doesn't mean the bacteria aren't causing disease in some area like the brain. Shy of a biopsy, however, or if fortunate, a CSF hit, the patient might never know.
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Think Jonathan has used the example of shingles --- once your immune system isn't functioning then the virus reappears --- so why hasn't it reappeared in ME/CFS?
Seem to recall Jonathan posting [last few days?] that viral persistence in the gut could explain covid symptoms? So perhaps there's a possibilty that persistence in gut would go unnoticed yet provoke symptoms?
 
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