The PolyBio Research Initiative: New ME/CFS research from some of the brightest young minds!

lenora

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PolyBio has some new talks posted on their website!

https://polybio.org/#section-presentations

Amy Proal: Introduction to PolyBio; ME/CFS & Long Covid/PACS research considerations

Michael VanElzakker: Studying the intersection of autonomic, neurovascular, & glymphatic systems

Matthew Anderson: Neuropathology study of immune penetration at the perivascular spaces in autism

Lena Pernas: Toxoplasma - mitochondria interactions, and Toxoplasma activity in COVID-19

Felix Ellet: Microfluidic devices visualizing host-pathogen interactions in Lyme

Resia Pretorius: Consequences of coagulation in COVID-19 and Long Covid

Marcelo Friere: Host-viral inflammatory responses in the saliva of COVID-19 patients

William Eimer: "Rethinking Alzheimer’s: Infection, amyloid, & innate immunity

@Pyrrhus....Hello. How do you keep up with all of this information? Do you remember it, or do you make notes or even save it? Thanks for doing it, as it's not easy to wade through reams of information.

I'll come back and read this later as I just finished a long report. They're always interesting, though, and it's good to have another source(s) of information. Yours, Lenora.
 

Pyrrhus

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PolyBio has some new talks posted on their website!

https://polybio.org/#section-presentations

Amy Proal: Introduction to PolyBio; ME/CFS & Long Covid/PACS research considerations

Michael VanElzakker: Studying the intersection of autonomic, neurovascular, & glymphatic systems
Here are the direct links to the video presentations!

Amy Proal:


Michael van Elzakker:
 

Pyrrhus

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NEW PAPER ON LONG COVID:

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (Proal and van Elzakker, 2021)
https://forums.phoenixrising.me/thr...te-to-persistent-symptoms-polybio-2021.84761/

Excerpt:
Proal and van Elzakker 2021 said:
The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 2019 (COVID-19). Across the globe, a subset of patients who sustain an acute SARS-CoV-2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months. These patients are being given the diagnosis Long COVID or Post-acute sequelae of COVID-19 (PASC).

It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms, none of which are mutually exclusive. This paper details mechanisms by which RNA viruses beyond just SARS-CoV-2 have be connected to long-term health consequences. It also reviews literature on acute COVID-19 and other virus-initiated chronic syndromes such as post-Ebola syndrome or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to discuss different scenarios for PASC symptom development.

Potential contributors to PASC symptoms include consequences from acute SARS-CoV-2 injury to one or multiple organs, persistent reservoirs of SARS-CoV-2 in certain tissues, re-activation of neurotrophic pathogens such as herpesviruses under conditions of COVID-19 immune dysregulation, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis.
 
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Pyrrhus

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NEW PAPER ON LONG COVID:

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (Proal and van Elzakker, 2021)
https://forums.phoenixrising.me/thr...te-to-persistent-symptoms-polybio-2021.84761/

Here are a few selected quotes from this excellent paper:
SARS-CoV-2 is a positive-sense single-stranded RNA virus (V’kovski et al., 2021). It is one of seven coronaviruses capable of infecting humans (Corman et al., 2018). Compared with other coronaviruses (e.g., HCoV-NL63, HCoV-229E, and HCoV-OC43) that are pathogenic to humans but generally drive only mild clinical symptoms, SARS-CoV-2 more closely resembles MERS-CoV or SARS-CoV (sometimes called SARS-CoV-1) in that it is capable of causing severe disease (Zhu et al., 2020).
[...]
Like all pathogens, SARS-CoV-2 employs a number of mechanisms to disable and evade the host immune response (Lucas et al., 2001; Bowie and Unterholzner, 2008; Taefehshokr et al., 2020). These include the ability to replicate within double-membrane vesicles that are not detected by host pathogen pattern recognition receptors (Taefehshokr et al., 2020). SARS-CoV-2 also dysregulates the host interferon response (Ribero et al., 2020). Interferons are cytokines secreted by host cells in response to viral infection. They bind to cell surface receptors and act as transcription factors, regulating the expression of hundreds of genes whose protein products target viruses at many levels (Acharya et al., 2020). SARS-CoV-2 expresses at least 10 proteins that allow it to either counteract the induction or escape the antiviral activity of interferons (Ribero et al., 2020), allowing the virus to better survive by rendering the host innate immune response inefficient.
[...]
Autopsy, animal, and organoid model studies show that, like SARS-CoV, SARS-CoV-2 is able to reach and infect cells of the CNS, infect neurons, and produce neuroinflammation (Matschke et al., 2020; Song et al., 2020; Song et al., 2021). Indeed, SARS-CoV-2 may be capable of transport up and down nerves and neuronal axons (Lima et al., 2020; Rangon et al., 2020; Song et al., 2020; Karuppan et al., 2021).
[...]
A growing number of studies show that some patients infected with SARS-CoV-2 do not successfully clear the virus over long periods of time (Liotti et al., 2020; Sun et al., 2020; Vibholm et al., 2021). In such studies, confirmation of SARS-CoV-2 in patient samples is generally assessed via identification of viral RNA and/or proteins. While identification of SARS-CoV-2 RNA could technically represent “inert” RNA, the possibility is unlikely because inert RNA in the human body is rapidly degraded (Houseley and Tollervey, 2009; Fabre et al., 2014). Nearly every human cell type, and human tears, saliva, mucus, perspiration, and extracellular spaces express RNAase enzymes that rapidly degrade inert RNA (Sorrentino, 2010; Gupta et al., 2013).
[...]
Persistence of SARS-CoV-2 in some patients with [Long Covid] symptoms is not unexpected. The literature is replete with examples of single-stranded RNA virus persistence, spanning decades of research on samples obtained from living human patients, autopsy studies, and animal studies (Viola et al., 1978; Riddell et al., 2007; Doi et al., 2016; Randall and Griffin, 2017; Ireland et al., 2020). Persistence of single-stranded RNA viruses in the central nervous system has been documented on multiple occasions. In a 1986 paper on the topic, Kristensson and Norrby explain that “Although it would seem difficult for RNA viruses to persist in the brain under conditions of normal immune defense mechanisms, representatives of at least seven of the established families of RNA viruses have been shown capable of causing persistent infections under these conditions” (Kristensson and Norrby, 1986).
[...]
Dozens of studies show coronaviruses capable of persistence, with some coronaviruses tied to chronic disease development (Arbour et al., 1999; Chan et al., 2004). One study found that in primates infected with two different coronaviruses, the viruses persisted, replicated, and disseminated in the central nervous system, leading to demyelination in the brain (Murray et al., 1992b). Coronavirus RNA and/or antigen have also been found in human multiple sclerosis (MS) brains examined at autopsy, including in both plaque and non-plaque areas of brainstem, cortex, and spinal cord samples (Murray et al., 1992a).
[...]
A number of teams have identified enteroviruses and their proteins in tissue samples obtained from patients with ME/CFS or ME/CFS-like symptoms (Yousef et al., 1988; Dowsett et al., 1990; Chia et al., 2010; Chia et al., 2015). For example, Chia and Chia found enterovirus VP1 protein and RNA in stomach biopsy specimens obtained from 165 ME/CFS patients with chronic abdominal complaints. 82% of ME/CFS specimens stained positive for enterovirus VP1 protein, compared to 20% of control specimens (Chia and Chia, 2008) (Figure 2). A non-cytolytic form of enteroviral infection was cultured from 5 ME/CFS specimens. Positive staining was found in repeat stomach biopsy specimens taken from 6 ME/CFS patients at the onset of symptoms and again 2–8 years later.

Enteroviruses have also been found in ME/CFS brain and muscle tissue (Cunningham et al., 1991; Gow et al., 1991; Richardson, 2001). For example, McGarry et al. (1994) examined the central nervous system of a woman with ME/CFS who died by suicide for the presence of enteroviruses. Positive PCR sequences with similarity to coxsackievirus B3 were identified in brain samples from the hypothalamus and brainstem, and also in muscle and heart samples. No enteroviral sequences were identified in any tissue obtained from four control subjects.
[...]
It is well understood that humans accumulate persistent viruses over the course of a lifetime. These viruses generally persist in dormant, latent, or non-cytolytic forms, but may reactivate under conditions of stress or immunosuppression. Indeed, people regarded as healthy have been shown to harbor a wide range of persistent viruses in blood, saliva (Wylie et al., 2014), or tissue that are capable of activation under such conditions (Virgin et al., 2009).
[...]
Acknowledgments
Thank you to supporters of PolyBio Research Foundation.
 
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lenora

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Thanks, Pyrrhus, I found the above particularly helpful in pointing out that things such as ME are not caused by one virus (or other causes) only. I've long thought that must be the case and it's helpful to hear someone like Dr. VanElzakkerk back it up.

True, 10 people may have the same cause of a problem, but 11-15 may have something else entirely. This doesn't mean that we shouldn't be happy when a cure is found for 1-10, just that we have to understand that the others still need more research and answers.

Virus activity has been thought to be harmless for far too many years. We should all be aware of the interlink between the virus and the illness....and whether or not it truly ever goes away. Yours, Lenora.
 

sometexan84

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Thanks, Pyrrhus, I found the above particularly helpful in pointing out that things such as ME are not caused by one virus (or other causes) only. I've long thought that must be the case and it's helpful to hear someone like Dr. VanElzakkerk back it up.
That's true, but I think it's important to point out that most are positive-sense single-stranded RNA viruses.

Like the chart shared here. And even in the video, VanElzakker mentions Zika and Ebola, those are actually both in the Flaviviridae family as well. So, all in that same group.

1628554695029.png
 

sometexan84

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A new presentation by Dr. Michael VanElzakker, which he recently gave to the Massachusetts General Hospital and the Brigham Clinical Trials Tools COVID-19 working group:

“What Long Covid may be and how to study it: Learning from ME/CFS"
Oh my god he is so freakin smart!

I've thought before VanElzakker is my favorite ME/CFS researcher, but this solidifies it. I am jealous of his intelligence.

This guy may not be on the verge of a "cure" as that's not necessarily his focus, but he's likely to be the first to figure out the pathophysiology of ME/CFS.
 

SNT Gatchaman

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Oh my god he is so freakin smart!

I've thought before VanElzakker is my favorite ME/CFS researcher, but this solidifies it. I am jealous of his intelligence.

This guy may not be on the verge of a "cure" as that's not necessarily his focus, but he's likely to be the first to figure out the pathophysiology of ME/CFS.
Just finished watching this video - fantastic. You can't help but be hopeful. Even if the neuroimaging modalities translating to clinically useful non-invasive diagnostics were all that transpired, that would be such a step forward.
 

bertiedog

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I feel that Van Elzakker presents the best all round explanation for our illness. It seems to me to cover everything and in the video he presented evidence to back up his statements. The only thing I don't think I heard mention was PEM but when you realise how much is going wrong in the specific areas of the brain stem that he illustrated, it doesn't take much imagination to realise PEM must always be just around the corner for each individual suffering with this illness to a great or lesser degree depending on one's own individual circumstances.

One thing in particular stood out for me was the example of when rats were injected with Campylobacter Jejuni they developed changes in the vagal circuit which affected the central autonomic pathways. The rats then exhibited sickness behaviour, became listless, not interested in food or exercise. They also exhibited a stress response as if they were suffering with anxiety and/or depression but it was pointed out that this was A RESULT OF THE INFECTION and not because they had a psychosomatic reaction. (After all they were rats and not human! My thoughts). He stressed the the psychologists had completely got this round the wrong way and did ME patients a massive dis-service.

He explained that the vagus nerve is affected by acute infection via the Microbiota-Gut-Brain axis.

This struck a cord with me because although I had many endocrine issues after 2 weeks of flu in 1979 which caused serve vertigo/migraine/anxiety attacks I had fairly good energy. But this all changed when in October 1998 I had a severe bout of Campylobacter poisoning, confirmed by my GP after a stool test. I was bedridden and extremely ill for around 2 weeks.

Within a year of this I started having huge bouts of hypoglycaemia when I was walking my dogs. These were so severe I could hardly get back to the car when walking on the beach and I felt completely helpless as I was so dizzy and couldn't see how I could get back to my car. I walked like somebody drunk and couldn't walk straight. Obviously I had a massive stress response every time this happened.

This was the start of real ME with very severe autonomic symptoms and an inability to walk for more than 20 minutes which has never improved and I had to give up my part teaching by early 2000. Thankfully I got help with the endocrine issues which have hugely improved and for which I am so grateful but my immune system etc remains badly affected along with POTS, severe migraines etc.

Thanks so much for posting these videos @Pyrrhus , they really are encouraging.

Pam
 

Violeta

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That's true, but I think it's important to point out that most are positive-sense single-stranded RNA viruses.

Like the chart shared here. And even in the video, VanElzakker mentions Zika and Ebola, those are actually both in the Flaviviridae family as well. So, all in that same group.

View attachment 44325
Do you mind if I ask why you pointed out about the viruses being single stranded RNA? Do you think the different categories of viruses can cause different types of ME/CFS? And do you know where EBV would be on that chart?

I am trying to figure out why some people have hypertension and some people have hypotension. Long COVID seems to involve hypertension. (I haven't had COVID, and I am on the hypotension spectrum)

I suppose the vagus nerve can be involved in both hyper and hypo tension, but what is causing the difference?
I will keep looking, but maybe someone can help by pointing me in a certain direction.
Thank you
 

lenora

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HI......at one time I was severely hypotensive, I mean under 90 systolic. After an early menopause at age 42, I went in the exact opposite direction and was declared hypertensive. And these were high numbers.

I'm now on meds and have evened out at anywhere from 110 to 145, about normal for me. However, it wasn't/isn't unusual for me to sometimes hit 300 or above. I do have epilepsy....does that have any bearing on it? This didn't occur until my later years (72, I'm now 74) and that's oddly enough when my BP evened out to what it is today, bearing in mind that I do use meds. I'm exhausted most of the time and personally, I put it down to low hypertension. Crazy, maybe, but perhaps we're not all meant to have such numbers.

I'm open in thought as to what the causes may be. Hormonal? Who knows.
 

sometexan84

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Do you mind if I ask why you pointed out about the viruses being single stranded RNA? Do you think the different categories of viruses can cause different types of ME/CFS? And do you know where EBV would be on that chart?
Because there appears to be a strong connection between chronic post-viral illness (including ME/CFS and LC), and these types of viruses. I thought it was interesting how closely related they are.

EBV is herpesviradae, on the opposite side of the chart.
 

Pyrrhus

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