Persistence of RNA viruses is deadly real

Pyrrhus

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Remember the large Ebola virus outbreak in West Africa that started in 2013?

Remember how many doctors went to West Africa to help contain the outbreak?

Remember that Scottish nurse that contracted Ebola in West Africa, returned home, was fully treated and then their doctors declared the Scottish nurse "Ebola-free"?

Remember how, months later, the Scottish nurse had vision problems and their doctors found Ebola virus persisting in their eye? How the doctors, once again, fully treated the Scottish nurse and again declared the Scottish nurse "Ebola-free"?

Remember how, a year later, the Scottish nurse had meningitis and their doctors found Ebola virus persisting in the cerebrospinal fluid? How the doctors, once again, fully treated the Scottish nurse and once again declared the Scottish nurse "Ebola-free"?

Well...

There is currently a new outbreak of Ebola virus in Guinea, in West Africa, and the journal Science published this article:

New Ebola outbreak likely sparked by a person infected 5 years ago
https://www.sciencemag.org/news/202...ak-likely-sparked-person-infected-5-years-ago

Excerpt:
Science journal said:
An Ebola outbreak in Guinea that has so far sickened at least 18 people and killed nine has stirred difficult memories of the devastating epidemic that struck the West African country between 2013 and 2016, along with neighboring Liberia and Sierra Leone, leaving more than 11,000 people dead.

But it may not just be the trauma that has persisted. The virus causing the new outbreak barely differs from the strain seen 5 to 6 years ago, genomic analyses by three independent research groups have shown, suggesting the virus lay dormant in a survivor of the epidemic all that time. “This is pretty shocking,” says virologist Angela Rasmussen of Georgetown University. “Ebolaviruses aren’t herpesviruses”—which are known to cause long-lasting infections—“and generally RNA viruses don’t just hang around not replicating at all.”

Scientists knew the Ebola virus can persist for a long time in the human body; a resurgence in Guinea in 2016 originated from a survivor who shed the virus in his semen more than 500 days after his infection and infected a partner through sexual intercourse. “But to have a new outbreak start from latent infection 5 years after the end of an epidemic is scary and new,” says Eric Delaporte, an infectious disease physician at the University of Montpellier who has studied Ebola survivors and is a member of one of the three teams. Outbreaks ignited by Ebola survivors are still very rare, Delaporte says, but the finding raises tricky questions about how to prevent them without further stigmatizing Ebola survivors.
 

Pyrrhus

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Possibly related:

‘Long-haul’ covid-19 complications are real. I faced similar problems after surviving Ebola.
Washington Post article by Craig A. Spencer
September 19, 2020
https://www.washingtonpost.com/heal...c2fd20-f45c-11ea-bc45-e5d48ab44b9f_story.html

Excerpt:
Washington Post said:
As a doctor who treated hundreds of covid-19 patients in New York and sees them frequently in the emergency room, I know how this virus touched nearly every organ system, and how many still haven’t recovered months after their initial illness. But in a sense, I’m also a long-hauler myself.

In 2014, I fell ill with Ebola after taking care of patients in Guinea. I spent 19 days in the hospital, and thankfully ultimately survived. But for months I had joint and muscle pains. It hurt to walk. My hair fell out in chunks. All of that got better.

But some things didn’t.

To this date, nearly six years after my “recovery,” I continue to experience difficulty concentrating. My ability to create new memories is drastically reduced. I forget names and details of people I knew very, very well. And in the past six years, it hasn’t gotten any better.
 

Pyrrhus

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A thought-provoking article from The Atlantic:

You Probably Have an Asymptomatic Infection Right Now
No, not COVID-19. Many, many viruses can infect humans without making us sick, and how they do that is one of biology’s deepest mysteries.
APRIL 7, 2021
https://www.theatlantic.com/science...-can-infect-us-without-making-us-sick/618530/

Excerpt:
The Atlantic said:
One of the most perplexing and enduring mysteries of the pandemic is also one of the most fundamental questions about viruses. How can the same virus that kills so many go entirely unnoticed in others?

The mystery is hardly unique to COVID-19. SARS, MERS, influenza, Ebola, dengue, yellow fever, chikungunya, West Nile, Lassa, Japanese encephalitis, Epstein-Barr, and polio can all be deadly in one person but asymptomatic in the next.

But for most of human existence, we didn’t know that viruses could infect us asymptomatically. We didn’t know how to look for them, or even that we should. The tools of modern science have slowly made the invisible visible: Antibody surveys that detect past infection, tests that find viral DNA or RNA even in asymptomatic people, and mathematical models all show that viruses are up to much more than making us sick. Scientists now think that for viruses, a wide range of disease severity is the norm rather than the exception.
 

Pyrrhus

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...And now we have a new paper in Nature that is really making some waves:

Scientists set out to connect the dots on long COVID (Marx, 2021)
https://www.nature.com/articles/s41592-021-01145-z

Excerpt:
Nature Methods said:
With grit, urgency and creativity, scientists address the puzzle of long-haul COVID.
[...]
Data are still emerging, says Karolinska Institute researcher Petter Brodin, but to a first approximation it appears that 70–80% of people experiencing severe acute reactions to COVID-19 are men, whereas women comprise 70–80% of those suffering from long COVID.
[...]
For example, autoantibodies could play a part, with the immune system attacking the body as it does in rheumatoid arthritis3. Perhaps viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition.
[...]
Even months after an infection, mRNA from SARS-CoV-2, as well as viral protein, have been detected in the intestines of infected individuals.
[...]
Four months after onset of COVID-19, immunofluorescence and PCR analysis of intestinal biopsies showed persistence of viral RNA and protein.
[...]
Susan Weiss at the University of Pennsylvania has long studied coronaviruses, and she wants to learn more about the persistence of SARS-CoV-2 and viral RNA. RNA does not integrate into the host genome, she says, but when a mouse is infected with murine coronavirus, viral RNA can persist in its central nervous system (CNS) without infectious virus being present. The virus infects the liver and the CNS, but persists just in the CNS. This has puzzled the field “for decades,” she says. The RNA can remain for the mouse’s whole lifetime, and “this is associated with demyelinating disease,” says Weiss. There is “no evidence at all for this in humans so I don’t really want to make an analogy—just an interesting fact.” Brodin believes that intense study of viral reservoirs, viral persistence and related aspects should be a focus in long COVID and beyond, for example for diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
[...]
“The virus may be gone, but the music lingers on,” says [Avi] Nath. “What is lingering: is it the immune system that is lingering or is it parts of the virus that are lingering?” He has encountered many people with symptoms after a viral infection that were assumed to be immune-mediated conditions. He recalls one person who was part of the NIH Undiagnosed Diseases Program and was experiencing dementia-like symptoms. The team performed whole-exome sequencing, immunoprofiling; they studied immune cells in his blood. With a phage-display method, they looked in his cerebrospinal fluid and blood for immune cells that target dengue virus and checked for autoantibodies; they assessed metabolites and tested for infectious diseases; they gave him drugs used in multiple sclerosis. The assays were inconclusive, the symptoms didn’t cease and the man passed away. The autopsy revealed that in the man’s brain, “there was dengue virus all over the place,” says Nath. Using immunohistochemistry, in situ hybridization, quantitative PCR and sequencing, the scientists found the virus had persisted in his central nervous system and brain, and it appeared this had led to panencephalitis and progressive dementia.
[...]
Months, even years, after recovering from measles, some children develop a deadly condition called subacute sclerosing panencephalitis (SSPE). Hunting for virus in the sick child’s body yields no findings. At autopsy, “you look at the brain, it’s loaded with the virus,” says Nath. What has taken place is that measles virus remains in the brain and it has mutated to the point at which it no longer forms a complete viral particle. It replicates only in a restricted form: it will form some RNA, some proteins and “it even has the ability to go from cell to cell,” he says. The changes allow the restricted virus in one neuron to fuse itself, along with its RNA and protein, with the cell membrane of a neighboring neuron. It keeps moving, infecting a succession of neurons.
(emphasis added)
 

Alvin2

The good news is patients don't die the bad news..
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junkcrap50

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A new paper in Nature that is really making some waves:

Scientists set out to connect the dots on long COVID (Marx, 2021)
https://www.nature.com/articles/s41592-021-01145-z

Excerpt:

(emphasis added)
This was a great article and find! If only we could test CFS people's brains for viruses. We need more autopsy studies done! Why isn't spinal fluid (CSF) in CFS patients testing more common? Aside from spinal taps are invasive, not pleasant procedures. Dr. Peterson does spinal taps on all his patients.

Random, crazy wild thought: Could you biopsy the brain? They do for brain tumors. Any CFS patients have a brain tumor or brain surgery?

EDIT: I did not mean to suggest to biopsy with CFS as the only reason. Of course that's unethical. But someone may have had it done for other reasons while having CFS.
 
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livinglighter

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If my recollections are correct the technology also isn’t available to directly detect neuroinflamation in the brain.

Why isn't spinal fluid (CSF) in CFS patients testing more common? Aside from spinal taps are invasive, not pleasant procedures. Dr. Peterson does spinal taps on all his patients.
Good question. Spinal taps don’t always provide the full picture though. I recently read encephalitis spinal taps can come back as normal. ME/CFS people must hold the record title amongst people ill with normal results. I think because of this many doctors decide to treat without extensive testing. I would like a spinal tap but I’m no longer optimistic that something will be found. But I think it should be done to help rule things out.

Random, crazy wild thought: Could you biopsy the brain? They do for brain tumors. Any CFS patients have a brain tumor or brain surgery?
Perhaps the means justify the method when you can see the tumour via imaging or some other abnormal testing results.
 

Pyrrhus

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Why isn't spinal fluid (CSF) in CFS patients testing more common?
The problem is that cerebrospinal fluid (CSF) will only tell you what's going on inside the blood-brain barrier, it won't tell you about what's going inside the brain,

There is a common misconception that the brain sits in CSF and therefore debris from the brain washes into the CSF. As long as the blood-brain-barrier is intact, this is not true.

The latest model of fluid flow shows that any debris from the brain will be washed into the lymph nodes at the base of the neck, NOT into the CSF as long as the blood-brain-barrier is intact:

1620237060555.jpeg



Random, crazy wild thought: Could you biopsy the brain?
These days, it is generally considered unethical to biopsy the brain...

...but, you CAN biopsy any swollen lymph nodes at the base of the neck!

If my recollections are correct the technology also isn’t available to directly detect neuroinflamation in the brain.
The only technology available to detect neuroinflammation in the brain is PET with special tracers targeting the TSPO protein in brain tissue-resident macrophages. This technology is only available in the research setting, and is not available to patients.

Even in the research setting, it's very difficult to perform this analysis because it requires a facility with a cyclotron (a small particle accelerator), an on-call staff of organic chemists, special machines that can perform both MRI as well as PET, and a team of bioinformaticians to correctly interpret the data.

More information:
Second study might confirm neuroinflammation in ME subcortical brain
https://forums.phoenixrising.me/thr...roinflammation-in-me-subcortical-brain.80923/
 
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livinglighter

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...But, you CAN biopsy any swollen lymph nodes at the base of the neck!
Has this been done in ME/CFS patients?

I have this handout I’ve been meaning to share from an NHS immunology fatigue clinic displaying the underlying pathology of CFS. The therapist at the time explained it’s not the whole picture but what was currently known to have involvement. I’ll post it and do my best to recount what was said to me but it mentions something to do with lymphocytes. I don’t get swollen lymph’s though.