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Over the past few months I have compiled a list of all Enterovirus associated diseases. Some of these are broad (as in other diseases / viruses can cause them), some are speculation, but a majority are confirmed to be associated or semi-associated (i.e. multiple possible pathologies). I also included some very important symptoms/predispositions that I think are noteworthy in our case.
I recently did a WGS with Nebula and was absolutely floored when I saw I was predisposed to almost all of these, which indicates a common denominator. It is a big clue.
Legend:
[B] = Broad, not the sole virus or driver known cause this disease
[C] = Confirmed, only virus or driver known to cause this disease
[P] = Predisposure or symptom allowing or proving the persistent infection
[S] = Speculation or conflicting evidence
ENTEROVIRUS ASSOCIATED DISEASES:
Ulcerative Colitis [C]
Not much to say about this one, cut and clear. All IBDs, including UC are pretty much confirmed enterovirus. A small select few of Dr. Chia's healthy controls that test Enterovirus positive have this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828589/
Rheumatoid Arthritis [B]
This one is caused by multiple processes and viruses, however, usually the self limiting RA, which is to say, the RA that has no symptoms and doesn't progress is usually viral. With a mildly positive Rheumassure panel (usually the 14-3-3 protein) and even collagen type 2 antibodies, Enterovirus should be a prime suspect.
Actually, I'm now seeing all respiratory infections could drive RA or create those same abs and proteins seen in RA. And COVID and EV are respiratory.
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1977-9
And here the 14-3-3 protein is noted to interact with VPs (viral proteins). The protein that ALL Enteroviruses use is VP1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232403/
And also here, collagen is required for enteroviruses to thrive, yet they also destroy it. So, they could theoritcally make these antibodies.
Not saying all cases of RA are viral, but seems like if you have the non-specific, self-limiting version, then clearly you should be curious. It appears to be a big case for viral. Especially if it was a sudden onset and you didn't have these RA markers prior.
Osteoarthritis [B]
Pretty much the same evidence as above, covers all forms of arthritis.
https://sci-hub.se/https://link.springer.com/article/10.1007/s00296-009-0891-x
Kawasaki Disease [B]
Again, like above, pretty much all respiratory viruses can cause this kind of disease. Also note that this is seen mostly in children and enteroviruses are often caught as a child. I'll get into why MECFS is usually at a later onset below, but it has to do with your gut barriers and how your body develops.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125523/
SLE (Lupus) [B]
Ah, Lupus. Okay, so, Lupus is a super interesting one not just because it can be caused by multiple viruses, but because interferon alpha has a large role in the development and progression of this illness. This is another reason why Interferon Alpha, you see these cases of people with Hepatitis who take IFN Alpha, right, and some go on to develop "Lupus like" syndrome and some also go onto, believe it or not, develop CFS. Interferon Alpha is an important cytokine, but in high levels can cause all sorts of issues, I would never recommend someone try alpha. Lambda is far superior. Even Beta, which is also a type one interferon is much safer than alpha. That should tell you enough.
Anyways, with that out of the way, the main viruses known to cause Lupus are: Herpesviruses like EBV, CMV, etc. Coxsackie B (Enterovirus), Rotavirus, Retroviruses like Influenza, and Parvovirus B19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581196/
https://pubmed.ncbi.nlm.nih.gov/33320244/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743115/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083591/
https://www.sciencedirect.com/science/article/abs/pii/009012299290250R
https://lupus.bmj.com/content/6/1/e000270#:~:text=Interferon in SLE&text=16 Observational studies found that,and induce an autoimmune disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/
Multiple Sclerosis [S]
Okay, onto MS, which is our first speculative one. I keep it as speculation because recently there has been growing evidence, and a remission case, after treating EBV. The patient got a remission after doing a T-Cell transplant with ATA-188. This transplantation completely eradicated the EBV infection and sent the patient into remission. That being said there is some evidence of enteroviruses playing maybe a minor role in it, but again, due to the recent remission case this is more speculation.
https://www.science.org/doi/10.1126/science.abj8222
https://www.socialpost.news/multiple-sclerosis-the-new-immunotherapy-in-phase-i-trials-stop-it/
https://www.msaustralia.org.au/news/ata188-experimental-treatment-progessive-ms-improvements/
https://pubmed.ncbi.nlm.nih.gov/19444695/
That last paper shows that there may be a link to MS and "MS like" diseases with Coxsackie B virus... But then, there is also this paper that says there was no Enteroviral RNA in CSF... However, I think they didn't really measure it properly as it isn't always in the CSF. Like, in our case it is in tissues and nerves, and blood sometimes... But only a specific neutralization method for blood should be used to detect it. So again, rather inconclusive.
https://pubmed.ncbi.nlm.nih.gov/16128872/
Also, one could argue that Enteroviruses were actually causing the EBV to remain persistent, which I will get to later on.
ALS [S]
This kinda ties in above, but there is at least more evidence of EV D68 and EV A71 possibly playing a role here, but the data thus far is conflicting. This article does conclude that EV was found and that broad-spectrum antiviral therapy was somewhat effective in patients with ALS. Based on these results, one would think that this is enough evidence to make a reasonable conclusion.
https://www.frontiersin.org/articles/10.3389/fnmol.2018.00063/full
However, there was also a recent linking of this disease to Toxoplasma...
https://alsnewstoday.com/news-posts...GsNY9eciGYG-dEyqVXrNcCAWpSzovCOrCGg183A93J9NY
So again, conflicting. And based on other papers, I wouldn't be surprised if there are multiple pathogens, like, working together to create ALS. Or maybe just different subsets and causes... So, my theory is Toxoplasma and EV BOTH have a role to play in this disease. But, again, pure speculation for now.
Parkinson's [C]
This is going to shock many of you. Many of you were probably expecting speculation or broad spectrum, but that is simply not the case here. In fact, Parkinson's is a pretty common neurological comordbidity alongside ME/CFS or "Parkinson's like" syndrome, strictly speaking for the neurological subset. I know a decent amount of people with ME/CFS who have a family history of the disease as well, but what makes me so confident it is caused by an enterovirus? Well, for starters 100% of brain autopsies have come back EV positive. Then we have evidence of the viral particles in the brain stem and neurons infected by enteroviruses. Lastly, in Parkinson's low dopamine and/or dopamine dysfunction is found to be a major player in the pathology of the disease, kinda like in ME/CFS... And we know these viruses deplete dopamine as a strategy because dopamine is an important immunomodulator. There are a surprising amount of similarities of Parkinson's in comparison to ME/CFS, but in Parkinson's it is like the neurons themselves have been hijacked, and in ME/CFS, we haven't quite gotten to that stage yet, for a majority.
Anyways, a chronic viral infection means that any dopaminergic upregulation will be met with viral insult. It basically conditions the arousal system towards a hypoactive state by sheer immune punishment.
And, please correct me if I'm wrong, but I have yet to see as much damning evidence for a virus or pathogen causing this disease as much as Enteroviruses... And when I say damning, I mean like autopsy of the brain, some sort of evidence that yes, indeed the virus is there not that it might be there. There have been theories of other viruses causing it like JEV, Influenza, and others, but EV has by far shown the most solid evidence I have seen so far.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968367/
https://www.mdpi.com/2076-2607/10/3/599/pdf?version=1646918067
https://www.researchgate.net/figure...13017-case-number-2369259-The_fig10_324906367
https://pubmed.ncbi.nlm.nih.gov/26115165/
Elevated or Lowered Apolipoprotein B levels [P]
This is a symptom, sign, or possible predisposition. But I have now seen quite a few patients with elevated levels of this now. Basically, if you have high levels it can indicate a risk for chronic cardiovascular diseases and possibly chronic infection and lowered ones can cause susceptibility to infection and/or severe infection.
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00086-6/fulltext
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00120-3/fulltext
https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=apolipoprotein_b100#:~:text=Normal levels of ApoB-100,done with the ApoB test.
Addison's disease [B]
Also known as "Adrenal Insufficiency", this disease has been associated with various pathogens including mycoplasma, mold spores, bacteria, parasites, CMV, COVID and Enteroviruses. Not all cases are infection related, only about half.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893984/
https://pubmed.ncbi.nlm.nih.gov/22801223/
https://casereports.bmj.com/content/14/1/e237690
Hashimoto's (High TSH) [B]
Enteroviruses are specifically noted to cause Hashimoto's by attacking the thyroid glands, however, there is some additional evidence pointing towards EBV, HSV (1 and 2) and HHV-6 causing this as well. Other viruses with insufficient evidence include Parvovirus B19 and Measles.
Also, this is rather a common comorbidity with ME/CFS.
https://www.boostthyroid.com/blog/2018/8/8/viruses-and-hashimotos
https://www.mdpi.com/2076-2607/9/4/876/pdf
Lastly, there is this study noting 11% had EV RNA in blood vs 0% healthy controls, which is small but still notable especially when you consider it was a much older article/study and they didn't have the testing methods for EV like we do now, like the VP1 protein stomach biopsy stain.
https://www.liebertpub.com/doi/abs/10.1089/thy.2019.0607?journalCode=thy
Grave's (Low TSH) [B]
Okay, so this is the exact opposite of what Hashimoto's is, but it's the same idea and there is far more evidence linking EV to Grave's disease than Hashimoto's...
https://pubmed.ncbi.nlm.nih.gov/23280563/
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/23280563/
Then there is some other evidence suggesting that EBV, HSV-1, Measles, Rubella, Parvovirus B19, and Retroviruses like HTLV-1 and SV40 may contribute to the development of Grave's disease.
https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-6-5
https://www.liebertpub.com/doi/10.1089/vim.2010.0072#:~:text=In Graves' disease, the IgG,lymphocytes, and is occasionally reactivated.
High IL-19 levels [P]
This is a weird one, but essentially high IL-19 can indicate TH1/TH2 imbalance and that is very significant in the development of ME/CFS.
https://pubmed.ncbi.nlm.nih.gov/22103848/
https://pubmed.ncbi.nlm.nih.gov/12370360/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276674/
Primary Billary Cholangitis [S]
Okay, so, this one is interesting because it involves the liver and the smaller little bile ducts getting slowly destroyed. There is some evidence of bacterial agents such as E. Coli and others doing this and also possible Retroviruses causing this too.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300644/
However, this next article shows that Coxsackie B4 Virus, Herpes Simplex Virus 1 (HSV-1) and Adenovirus 2 also had the potential to cause this pathology. So, the evidence is here that many pathogens can cause this, however, there isn't enough evidence in my honest opinion to make a reasonable conclusion.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166250/
So, the evidence for EVs case is quite poor, but it is clear that some sort of pathogen or even multiple pathogens can cause this disease.
Vitiligo [S]
Okay, so this is one of these cases where we have to connect the dots and 'bridge' the gaps in the research papers.
https://pubmed.ncbi.nlm.nih.gov/23382179/
So here we see that in vitiligo the NLRP1 inflammasome is incredibly important in developing this disease. Well, then we have this next article that shows EV can activate this pathway via the 3C protease that Enteroviruses have...
https://www.science.org/doi/10.1126/science.aay2002
But, there is no direct evidence yet, so it remains skeptical, but I would wager it is largely caused by Enteroviruses.
Also, there is more evidence pointing towards herpesviruses and even HIV.
https://medwinpublishers.com/VIJ/VIJ16000181.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134483/
Crohn's disease [C]
Alright, this is yet another Inflammatory Bowel Disease (IBD) like UC that is found in Chia's healthy controls that test positive in the stomach biopsy for the Enteroviral VP1 protein. And, not only that, 9 out of 9 (100%) of Crohn's disease patients were tested Colon biopsy positive for BOTH Coxsackie B Virus and Echovirus!
This 2013 study is what shows they found Enterovirus in colon and Ileum (last part of small intestine, before large intestine/colon)...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696939/
So, clearly CVB and Echo have tropism here.
However, they may have found other enteroviruses in this study as well...
They mention finding HEV, Human Enterovirus (generic) in many of the patients, but didn't talk too much about it becuse the focus of their study was to look specifically for CVB and Echo.
https://www.sciencedaily.com/releases/2013/06/130627102827.htm#:~:text=Summary:,this chronic inflammatory intestinal disorder.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828589/
And here Dr. John Chia notes that specifically Echovirus 18 is associated with Crohn's disease.
https://www.scirp.org/journal/paperinformation.aspx?paperid=94556
Celiac disease [C]
This one is a little odd, there is conflicting evidence that Adenovirus may cause this disease, but it seems there is very solid evidence that Celiac itself is caused by EV. Also, many patients report sudden gluten Intolerance that coincides with their ME/CFS onset... This isn't a coincidence, there is a clear link between Celiac and "Celiac like" diseases and EV.
https://www.sciencedaily.com/releases/2019/02/190213192455.htm#:~:text=FULL STORY-,A common intestinal virus, enterovirus, in early childhood may be,risk of later coeliac disease.
https://www.frontiersin.org/articles/10.3389/fimmu.2020.604529/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884453/
Which explains why even in the acute Enteroviral infections some develop temporary gluten intolerance that later goes away after the infection is cleared.
Myasthenia Gravis [B]
So, this one is kind of crazy because not only can Enteroviruses cause this disease but so can our good old friend EBV. But the evidence here is pretty damning so there isn't a whole lot to say, the articles speak for themselves. Remember that even if MG is caused by poliovirus, which is almost extinct at this point, it is still considered an Enterovirus! One of these also mention Rhinovirus, which is known to cause the common cold, also possibly playing a role in this disease. Rhinoviruses are also part of the Picornavirus family, so, again, Enteroviruses.
https://www.hindawi.com/journals/ad/2011/213092/
https://www.nature.com/articles/s41598-017-04993-y
https://pubmed.ncbi.nlm.nih.gov/20368632/
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [B]
Here it is, the one you all having been waiting for. So, if you haven't already I highly recommend watching this video by PolyBio, it pretty much explains the entire Enterovirus theory.
Here are some important MEpedia links as well...
https://me-pedia.org/wiki/List_of_enterovirus_infection_studies
https://me-pedia.org/wiki/Non-cytolytic_enterovirus
https://me-pedia.org/wiki/Autopsy_in_Myalgic_Encephalomyelitis
These list out all EV studies and show the importance of Non-Cytolytic Enteroviruses and why they are so critical in the pathology and development of MECFS.
Also note that 100% of brain autopsies found Enteroviral remnants in patients brains so far...
Obviously, other reasons have been proposed like herpesviruses, but as noted before, often these DNA (herpes) viruses are persisting because of the TH cell population imbalance and/or dysfunction. Chia finds almost 85% of his patients are EV positive vs 20% controls, which is significant. Other causes are structural issues, mold, and many many others. But, EV is by far the most common. And, again, I wouldn't be surprised if other ss+RNA viruses do this including COVID.
https://www.frontiersin.org/articles/10.3389/fmed.2021.688486/full#:~:text=Enteroviruses (EVs) as a cause,system, muscle, and heart.
https://pubmed.ncbi.nlm.nih.gov/8354926/
Irritable Bowel Syndrome (IBS) [C]
This one is fairly obvious. I mean, I hear over and over again the argument that these viruses are common, so why does it cause these diseases? Well, according to this article:
https://www.virology.ws/2018/12/27/...ic-nervous-system-and-intestinal-dysmotility/
Yes, 10-30% of people have IBS, that's quite a large amount and again Enteroviruses are common.
I really recommend reading that article because so many people narrow in on the Central Nervous System (CNS), but what is equally as important if not more important is the Enteric Nervous System (ENS).
IBS is also caused by Norovirus, which has been shown to become persistent and is very similar to Enteroviruses.
Also, this is yet another one of the diseases that Dr. Chia finds in his healthy controls when doing the stomach biopsy VP1 protein stain, which if 20% of controls are EV positive, that lines up with the population range we see here with IBS.
https://pubmed.ncbi.nlm.nih.gov/25431489/
https://www.seattletimes.com/life/w...go-away-it-might-be-irritable-bowel-syndrome/
https://www.researchgate.net/public...orovirus-Enterovirus_Gastroenteritis_Outbreak
https://www.genengnews.com/topics/t...r-protect-against-inflammatory-bowel-disease/
Coincidence that they consider CFS and IBS "post viral"...?
Hmmm... I think not!
Type One Diabetes (T1D) [C]
This one surprises many, but it's another very obvious one. Like, it has been proven, time and time again, that T1D is caused by Coxsackie B4 Virus. The average age of T1D onset is around the ages of 17-21 and the MECFS average age of onset is 19-23... That's not a coincidence.
https://pubmed.ncbi.nlm.nih.gov/18951821/
https://pubmed.ncbi.nlm.nih.gov/9662368/
https://www.pnas.org/doi/10.1073/pnas.0700442104
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276674/
This last article touches on why Interferon Alpha, actually makes CVB4 worse because of it's unique tropism.
Essentially, IFN alpha is ineffective for CVB4 because it inhibits IFN gamma which is important for specifically CVB4. This is why Chia finds his IFN therapy did not work on CVB4.
Acute Flaccid Myelitis [C]
Very recently has this been linked to Enteroviruses. It's often seen in children and often, again, EV is commonly contracted as a child. It is when the virus invades the CSF that you get this lovely disease. It is almost like polio... but not quite. Just note the similarities of what the CDC has to say about this illness:
https://www.cdc.gov/acute-flaccid-myelitis/index.html
https://journals.asm.org/doi/10.1128/mBio.01903-19
https://www.nih.gov/news-events/nih...virus-infection-linked-acute-flaccid-myelitis
Idiopathic Gastroparesis [C]
This is a fun one. So, in the very severe cases, the virus can infect your vagus nerve causing GP. And most "idiopathic" cases are really just EV. 9 out of 10 of idiopathic cases turned up to be EV and it seems a minor subset is also caused by your lovely neighborhood friend, Norovirus. The underlying mechanism is again, infection, likely through the CNS and/or ENS. Also, keep in mind these viruses love to travel up through the vagus nerve and use it like a highway to evade your immune system and reach places like your brain and eyes.
https://link.springer.com/article/10.1007/s10620-016-4227-x
https://pubmed.ncbi.nlm.nih.gov/27344315/
https://www.cureus.com/articles/21623-norovirus-induced-gastroparesis
Idiopathic Mast Cell Disease/Activation Syndrome [B]
Okay, so, we know mast cells are an important part of the immune system and immune defense, so if you have a chronic infection, it would make since you would also have a chronic mast cell issue, which, if you idneitfied the pathogen would actually make it secondary not idiopathic.
But, nonetheless, many viruses cause this to happen (usually acutely), but not in our case. Many pathogens also cause elevated tryptase. This is why MCAS is such a common comordbidity in us.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529115/
https://www.annallergy.org/article/S1081-1206(17)30850-5/pdf
https://www.microbiologyresearch.org/content/journal/jmmcr/10.1099/jmmcr.0.005012?crawler=true
GERD [B]
So, despite what many typically think of when they hear 'GERD' this is often, in our case, caused by low stomach acid. Which, is weird to think about at first, but seriously, think about it. A chronic viral infection such as EV will deplete your stomach acid due to the infected cells. Then, you get this reflux because there is not enough acid. But, why would PPIs help then? Well, remember, PPIs work by inhibiting the actual mechanism that our muscle in the esophagus uses and suppressed that "reaction" it is having due to, again, low stomach acid. So, by having a low amount of acid, it is essentially "gasping" for "air" (acid).
Obviously, other diseases and infections can cause this too, like H. Pylori.
https://www.enterovirusfoundation.org/the-symptoms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563291/
https://biopractica.com.au/a-nasty-little-bug-that-can-cause-heartburn-reflux/#:~:text=Helicobacter pylori, or H.,ulcers, and even stomach cancer.
Herpangina [C]
Often seen in children, this disease is similar, but distinct from HFMD. It is often caused by Coxsackie A and B virus as well as occasionally EV71A.
https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/herpangina#:~:text=Herpangina is a febrile disorder,also Overview of Enterovirus Infections
https://www.ncbi.nlm.nih.gov/books/NBK507792/
Dilated Cardiomyopathy [B]
Another disease that seems to be driven by Coxsackie B virus. I think Echovirus can also cause this as the article just mentions Enterovirus Group B, which seems to include Echoviruses.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.035966#:~:text=Group B enteroviruses are common,of dilated cardiomyopathy remain unclear.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056497/
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
Myocarditis [B]
Another cardiovascular one. Many viruses cause this including Adenovirus, Coxsackie B, and others. However, it seems Enteroviruses are the most frequent viral form of this disease.
https://heart.bmj.com/content/83/1/86
https://fn.bmj.com/content/89/5/F461
https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-12-212
https://www.ahajournals.org/doi/10.1161/circulationaha.108.766022
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135016/
https://www.frontiersin.org/articles/10.3389/fcimb.2016.00171/full
This last one shows that Coxsackie B3 caused th17 dysregulation which is another important thing in the development and maintenance of ME/CFS.
Functional Dyspepsia [C]
This one remained a mystery up until Dr. Chia came out with a study showing that this disease is associated with Enteroviruses.
https://www.scirp.org/journal/paperinformation.aspx?paperid=55465
Chronic Gastritis [C]
Same evidence as above, again, Chia coming in and showing how people underestimate EVs potential to cause diseases.
https://www.scirp.org/journal/paperinformation.aspx?paperid=55465
Aseptic Meningitis [B]
A handful of viruses can cause this problem, but, EV is by far the most common. No other virus comes close! Enteroviruses were 25% of the cases of Aseptic Meningitis compared to it's runner-up which was HHV-6 at 7.9% of cases.
https://emedicine.medscape.com/article/1169489-overview#:~:text=Viral infection,have been linked with meningitis.
https://www.frontiersin.org/articles/10.3389/fneur.2020.602267/full
Conjunctivitis [B]
Okay, so this one is very often Enteroviruses, specifically Coxsackie A24 and Enterovirus D70 generally. But, some other pathogens do this too. Just, most notably EV.
https://www.sciencedirect.com/topics/medicine-and-dentistry/acute-hemorrhagic-conjunctivitis#:~:text=Acute hemorrhagic conjunctivitis is a,and fine, punctate epithelial keratitis.
https://www.cdc.gov/conjunctivitis/clinical.html
Myopericarditis [B]
So, this one is often related to Coxsackie B. Obviously, other causes of this one as well. Notice how most of the heart related diseases are usually Coxsackie B. It is because this virus has tropism for those cells.
https://www.ajconline.org/article/0002-9149(74)90201-X/pdf
https://pubmed.ncbi.nlm.nih.gov/11808426/
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
Pericarditis [B]
Pretty much the same evidence as above with the additional note that both Coxsackie and Echovirus cause this, but wouldn't surprise me if other EV forms did as well or other ss+RNA viruses.
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
https://loinc.org/88538-4/#:~:text=Viral infections are a common,etiologies associated with viral pericarditis.
Hands Foot and Mouth Disease (HFMD) [C]
Not much to say here, besides it is common in children and often associated with Coxsackie A16 and Enterovirus 71A.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873753/
Encephalitis [B]
Pretty common severe acute symptom of infection. Many viruses can cause this, most notably herpes and enteroviruses, but certainly aren't just limited to these. I only included it because some people still deny it can penetrate the CNS.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044131/
https://www.mountsinai.org/health-library/report/viral-encephalitis#:~:text=These viruses include the herpes,most common cause of encephalitis.
https://www.frontiersin.org/articles/10.3389/fmicb.2020.00261/full
Paralysis [C]
I only put this down as solely Enterovirus because it is by far the most associated with this complication, like, no other virus comes close. Specifically, EV D68. And I really couldn't find any other cases of herpes or other exotic ss+RNA viruses doing anything similar. Polio also falls under this.
https://www.statnews.com/2019/06/14/acute-flaccid-myelitis-possible-cause-paralysis-kids/
https://www.frontiersin.org/articles/10.3389/fneur.2017.00638/full
Epididymitis [B]
Believe it or not, this is very often "post" infectious. Like, many cases of these are after acute infection. Which one would not think right away, as the testicles are an "immuno-privileged" site. Well, this is not always the case. I mean, there is even a case of a guy who survived EBOLA VIRUS who ended up transmitting the virus to someone sexually after FIVE YEARS which actually TRIGGERED A NEW OUTBREAK!
So, this is a broad disease, caused by many infections, but with Enteroviruses it seems to be Coxsackie Type A Virus most notably. I am sure COVID and other EVs and even any other forms of ss+RNA viruses can cause this annoying symptom/disease. Many with ME/CFS including myself note this symptom only pops up following exertion.
https://publications.aap.org/aapgra...7/87518/Epididymitis-is-Often-Post-Infectious
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313299/
https://www.livescience.com/ebola-lingered-survivor-sparked-outbreak.html
Poliomyelitis [C]
Yes, the three types of poliovirus are indeed Enteroviruses. According to the CDC about 0.5% to 1% of cases will actually go on to develop poliomyelitis... Again, I often here the argument that EV is common so why only a small percentage get ME/CFS? Well, that is like saying back in the 1900s that Poliovirus is common and why do only a select few get chronic poliomyelitis and paralysis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212416/
https://www.cdc.gov/polio/what-is-polio/index.htm
Hepatitis A [C]
This is another one that shocks many. So, early on this was initially classified as an Enterovirus 72, however, once they learned that other viruses caused Hepatitis it was later renamed to Hepatitis A. But, the fact still remains, this is an Enterovirus.
https://www.karger.com/Article/Pdf/149313
https://www.news-medical.net/life-sciences/Enterovirus-72-Infection.aspx
And recently, like, currently there is a Hepatitis A outbreak. Thankfully most everyone is vaccinated against it already.
https://www.clickondetroit.com/cons...-sold-at-kroger-walmart-other-grocery-stores/
Sjorgen's Syndrome [C]
Seems like EV has the most confirmed papers on this so far, most notably Coxsackie B4. Some minor indication retroviruses may play a role but not nearly enough evidence.
https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.20463
https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1313.090
https://www.robertfoxmd.com/SjogrensByFox/Sjogren's_syndrome-Infections_that_Mimic.pdf
Eosinophilic Esophagitis (EoE) [B]
EoE is a common comordbidity of MCAS and can be due to infection or primary MCAS and other diseases.
EoE can be driven by infection and so can MCAS. So, both can be primary or secondary. Eosinophils in blood usually don't represent what's in the tissues, so keep that in mind.
I strongly believe if you have ME/CFS and you have EoE, there is a solid chance that you have it caused by an infection.
Picornavirus Infection of Esophageal Epithelial Cells (Picornavirus is a family of viruses that include Enterovirus, Rhinovirus, etc.) can cause EoE.
https://www.jacionline.org/article/S0091-6749(19)32469-8/fulltext
This article explains how this infection is also in epithelial cells, in the esophagus. And that it expresses the IFNL1 receptor. This is for IFN-Lambda1, so Peginterferon Lambda 1a is effective on these receptors. And is the ONLY interferon that would work.
https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=134&ContentID=169
Iron Deficiency / Anemia [P]
Alright, so... Many viruses, in fact, most viruses will deplete your iron either by infecting the cells or inhibting the ability to functionally use that iron. And believe it or not, viruses rely on iron to survive.
https://www.sciencedirect.com/science/article/pii/S0098299720300224
https://jmhg.springeropen.com/articles/10.1186/s43042-020-00114-z
Dr. Chia also notes that many of his chronic EV patients become iron deficient.
https://www.enterovirusfoundation.org/the-symptoms
Pleurodynia [C]
This type of chest pain seems to go in epidemics following Coxsackie A and B Virus as well as Echovirus. So, it seems like basically all EVs can do this.
https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/epidemic-pleurodynia#:~:text=Epidemic pleurodynia is a febrile,is most common among children.
https://www.verywellhealth.com/pleurodynia-overview-4171796
Hypoxia / Low Blood Oxygen Levels [B]
Obviously a lot of things can cause this problem, but specifically Enteroviruses A71 and D68 are noted the cause this more than other EVs. Bacteria, parasites, and other viruses can also do this.
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0585-y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004002/
Fibromyalgia [B]
So, pretty much like ME/CFS, EBV and other viruses including Enteroviruses can cause this and research is now showing it is considered "post infectious".
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/14556267/
https://me-pedia.org/wiki/Fibromyalgia_notable_studies
Alzheimer's [S]
I only found one article, showing that broad-spectrum antiviral therapy and a specific medication, Pleconaril, which is active on EVs, improved some patients Alzheimer's. However, this is the only study, and I am sure other studies are floating around out there with other infectious agents or other theories in general. So, while I think this is a good start, it isn't enough to come to a sensible conclusion.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203284/
And... case in point! Here we have some evidence of bacterial agents, HSV-1, HHV-6, and HHV-7 (Herpesviruses) possibly playing a role here as well...
https://www.nature.com/articles/d41586-020-03084-9
Dementia [B]
While many of us may feel like we have dementia, Enteroviruses have been proven to cause rapid progressive dementia in a 28-year old...
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/26727905/
Of course, other pathogens like bacteria have been shown to possibly cause this as well.
https://www.frontiersin.org/researc...nships-between-infectious-agents-and-dementia
Reactivated / Persistent Herpes [C]
Alright, so, herpesviruses can reactivate for a lot of reasons like 'trauma', however, many of these stress cases actually just weaken the immune system leading to the virus seeing an opportunity. And in COVID and EVs cases, we see that it will reactivate due to these infections causing TH1/TH2 imbalance and now your immune system can not handle the virus naturally and it will persist until that dysfunction is fixed (i.e. getting rid of the persistent COVID or EV).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809354/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330347/
https://link.springer.com/article/10.1007/s00415-020-10265-z
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233978/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959425/
GPCR Auto Antibodies (CellTrend) [S]
Okay, so this is yet another one where we have to connect the dots. This will show the importance of the Enteric Nervous System (ENS).
It has to do with the fact that these neurotransmitters are in our gut lining, in the enteric nervous system and that damage here to cells, neurons and these neurotransmitters from Enterovirus, ends up creating these autoantibodies.
https://journals.physiology.org/doi/full/10.1152/ajpgi.00406.2018
We already know EV infects the neurons and cells in these areas. So we already can strongly theorize that when EV infects cells, it can create auto-antibodies to those cells, as well as the expressions on the surface of those cells (e.g. TS-HDS).
Then you have this, which shows that the ENS and CNS are almost identical!
https://en.wikipedia.org/wiki/Enteric_nervous_system
So, if the neurotransmitters are identical, then with reduced self-tolerance, the gut-brain-axis connection makes it EASY for there to be autoantibodies to these neurotransmitters in the BRAIN as well!
Which, the cause of this is all from the infection in the ENS.
However, there is no direct evidence, but I believe what has been shown here is very strong.
Small Fiber Neuropathy (SFN) [B]
Many viruses can cause autoimmune SFN (TS-HDS and FGFR3 aabs), including Enteroviruses and COVID. Usually this form of SFN is mild or borderline positive.
https://pubmed.ncbi.nlm.nih.gov/1322452/
https://pubmed.ncbi.nlm.nih.gov/34766365/
PEM [P]
Would you look at that, it's our favorite symptom! Okay, so, a lot of mitochondrial diseases and other genetic issues can cause this problem, heck, even chemotherapy people are noted to have PEM. However, many viruses are made much worse upon exertion, most notably Enterovirus, EBV, Norovirus, Rotavirus, HIV/AIDS and Parvovirus B19. So, most of these are ss+RNA viruses again and the reason I think that is is because of the ERK1 receptor.
So ERK1 is involved in viral replication and ERK1 is also activated by exercise...
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2005.103481
A lot of viruses infections including ebv, Enteroviruses, rotavirus, norovirus, and COVID (most of which are all RNA) get worse based on the above mechanism.
This makes sense.
A chronic viral infection means that any dopaminergic upregulation will be met with viral insult. It basically conditions the arousal system towards a hypoactive state by sheer immune punishment.
Growth and differentiation pathways enhance metabolic allocation to a cell, viruses depend on this metabolic allocation to replicate using the cell's machinery... So a global increase in growth and differentation activity triggered by physical or mental exertion would be an accessory to viral activity.
Also, dopamine is an important immunomodulator and it makes sense that viruses would use Dopamine Receptors (DRs) as part of their invasive schema... And many of us feel better on dopamine drugs like pregablin, abilify, many others...
https://pubmed.ncbi.nlm.nih.gov/2483440/
This shows that many patients have low aldosterone and dopamine. And according to CellTrend, almost 50% of patients have autoantibodies that antagonize the function (not level) of Angiotensin II, which would ALSO deplete your aldosterone, since Angiotensin II is what helps regulate and produce your aldosterone.
I know many cases, including myself, who have UNMEASURABLE aldosterone. Like, there was not a drop of it detected.
This both contributes to POTS and OI indirectly and directly.
And here, it looks like dopaminergic hyperactivity tends to increase viral replication with HIV, as well.
https://www.sciencedirect.com/science/article/pii/S0002944010606244
Finally, here is a brief overview of excerise exacerbating respiratory infections in general (this includes Enteroviruses)...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803113/
CONCLUSION:
Enteroviruses are by FAR the leading virus associated with diseases. Like, no other virus even comes close. Herpesviruses, the list I have for them dwarves in comparison to this, only about half. And COVID we don't know everything yet but it's trailing behind Herpesviruses from what I have seen and gathered thus far. So, yeah, they may be common, but there are also so many complications associated with them. There is a total of 52! Think about that...
I recently did a WGS with Nebula and was absolutely floored when I saw I was predisposed to almost all of these, which indicates a common denominator. It is a big clue.
Legend:
[B] = Broad, not the sole virus or driver known cause this disease
[C] = Confirmed, only virus or driver known to cause this disease
[P] = Predisposure or symptom allowing or proving the persistent infection
[S] = Speculation or conflicting evidence
ENTEROVIRUS ASSOCIATED DISEASES:
Ulcerative Colitis [C]
Not much to say about this one, cut and clear. All IBDs, including UC are pretty much confirmed enterovirus. A small select few of Dr. Chia's healthy controls that test Enterovirus positive have this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828589/
Rheumatoid Arthritis [B]
This one is caused by multiple processes and viruses, however, usually the self limiting RA, which is to say, the RA that has no symptoms and doesn't progress is usually viral. With a mildly positive Rheumassure panel (usually the 14-3-3 protein) and even collagen type 2 antibodies, Enterovirus should be a prime suspect.
Actually, I'm now seeing all respiratory infections could drive RA or create those same abs and proteins seen in RA. And COVID and EV are respiratory.
https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-1977-9
And here the 14-3-3 protein is noted to interact with VPs (viral proteins). The protein that ALL Enteroviruses use is VP1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232403/
And also here, collagen is required for enteroviruses to thrive, yet they also destroy it. So, they could theoritcally make these antibodies.
Not saying all cases of RA are viral, but seems like if you have the non-specific, self-limiting version, then clearly you should be curious. It appears to be a big case for viral. Especially if it was a sudden onset and you didn't have these RA markers prior.
Osteoarthritis [B]
Pretty much the same evidence as above, covers all forms of arthritis.
https://sci-hub.se/https://link.springer.com/article/10.1007/s00296-009-0891-x
Kawasaki Disease [B]
Again, like above, pretty much all respiratory viruses can cause this kind of disease. Also note that this is seen mostly in children and enteroviruses are often caught as a child. I'll get into why MECFS is usually at a later onset below, but it has to do with your gut barriers and how your body develops.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125523/
SLE (Lupus) [B]
Ah, Lupus. Okay, so, Lupus is a super interesting one not just because it can be caused by multiple viruses, but because interferon alpha has a large role in the development and progression of this illness. This is another reason why Interferon Alpha, you see these cases of people with Hepatitis who take IFN Alpha, right, and some go on to develop "Lupus like" syndrome and some also go onto, believe it or not, develop CFS. Interferon Alpha is an important cytokine, but in high levels can cause all sorts of issues, I would never recommend someone try alpha. Lambda is far superior. Even Beta, which is also a type one interferon is much safer than alpha. That should tell you enough.
Anyways, with that out of the way, the main viruses known to cause Lupus are: Herpesviruses like EBV, CMV, etc. Coxsackie B (Enterovirus), Rotavirus, Retroviruses like Influenza, and Parvovirus B19.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581196/
https://pubmed.ncbi.nlm.nih.gov/33320244/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743115/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083591/
https://www.sciencedirect.com/science/article/abs/pii/009012299290250R
https://lupus.bmj.com/content/6/1/e000270#:~:text=Interferon in SLE&text=16 Observational studies found that,and induce an autoimmune disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350004/
Multiple Sclerosis [S]
Okay, onto MS, which is our first speculative one. I keep it as speculation because recently there has been growing evidence, and a remission case, after treating EBV. The patient got a remission after doing a T-Cell transplant with ATA-188. This transplantation completely eradicated the EBV infection and sent the patient into remission. That being said there is some evidence of enteroviruses playing maybe a minor role in it, but again, due to the recent remission case this is more speculation.
https://www.science.org/doi/10.1126/science.abj8222
https://www.socialpost.news/multiple-sclerosis-the-new-immunotherapy-in-phase-i-trials-stop-it/
https://www.msaustralia.org.au/news/ata188-experimental-treatment-progessive-ms-improvements/
https://pubmed.ncbi.nlm.nih.gov/19444695/
That last paper shows that there may be a link to MS and "MS like" diseases with Coxsackie B virus... But then, there is also this paper that says there was no Enteroviral RNA in CSF... However, I think they didn't really measure it properly as it isn't always in the CSF. Like, in our case it is in tissues and nerves, and blood sometimes... But only a specific neutralization method for blood should be used to detect it. So again, rather inconclusive.
https://pubmed.ncbi.nlm.nih.gov/16128872/
Also, one could argue that Enteroviruses were actually causing the EBV to remain persistent, which I will get to later on.
ALS [S]
This kinda ties in above, but there is at least more evidence of EV D68 and EV A71 possibly playing a role here, but the data thus far is conflicting. This article does conclude that EV was found and that broad-spectrum antiviral therapy was somewhat effective in patients with ALS. Based on these results, one would think that this is enough evidence to make a reasonable conclusion.
https://www.frontiersin.org/articles/10.3389/fnmol.2018.00063/full
However, there was also a recent linking of this disease to Toxoplasma...
https://alsnewstoday.com/news-posts...GsNY9eciGYG-dEyqVXrNcCAWpSzovCOrCGg183A93J9NY
So again, conflicting. And based on other papers, I wouldn't be surprised if there are multiple pathogens, like, working together to create ALS. Or maybe just different subsets and causes... So, my theory is Toxoplasma and EV BOTH have a role to play in this disease. But, again, pure speculation for now.
Parkinson's [C]
This is going to shock many of you. Many of you were probably expecting speculation or broad spectrum, but that is simply not the case here. In fact, Parkinson's is a pretty common neurological comordbidity alongside ME/CFS or "Parkinson's like" syndrome, strictly speaking for the neurological subset. I know a decent amount of people with ME/CFS who have a family history of the disease as well, but what makes me so confident it is caused by an enterovirus? Well, for starters 100% of brain autopsies have come back EV positive. Then we have evidence of the viral particles in the brain stem and neurons infected by enteroviruses. Lastly, in Parkinson's low dopamine and/or dopamine dysfunction is found to be a major player in the pathology of the disease, kinda like in ME/CFS... And we know these viruses deplete dopamine as a strategy because dopamine is an important immunomodulator. There are a surprising amount of similarities of Parkinson's in comparison to ME/CFS, but in Parkinson's it is like the neurons themselves have been hijacked, and in ME/CFS, we haven't quite gotten to that stage yet, for a majority.
Anyways, a chronic viral infection means that any dopaminergic upregulation will be met with viral insult. It basically conditions the arousal system towards a hypoactive state by sheer immune punishment.
And, please correct me if I'm wrong, but I have yet to see as much damning evidence for a virus or pathogen causing this disease as much as Enteroviruses... And when I say damning, I mean like autopsy of the brain, some sort of evidence that yes, indeed the virus is there not that it might be there. There have been theories of other viruses causing it like JEV, Influenza, and others, but EV has by far shown the most solid evidence I have seen so far.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968367/
https://www.mdpi.com/2076-2607/10/3/599/pdf?version=1646918067
https://www.researchgate.net/figure...13017-case-number-2369259-The_fig10_324906367
https://pubmed.ncbi.nlm.nih.gov/26115165/
Elevated or Lowered Apolipoprotein B levels [P]
This is a symptom, sign, or possible predisposition. But I have now seen quite a few patients with elevated levels of this now. Basically, if you have high levels it can indicate a risk for chronic cardiovascular diseases and possibly chronic infection and lowered ones can cause susceptibility to infection and/or severe infection.
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00086-6/fulltext
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00120-3/fulltext
https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=apolipoprotein_b100#:~:text=Normal levels of ApoB-100,done with the ApoB test.
Addison's disease [B]
Also known as "Adrenal Insufficiency", this disease has been associated with various pathogens including mycoplasma, mold spores, bacteria, parasites, CMV, COVID and Enteroviruses. Not all cases are infection related, only about half.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893984/
https://pubmed.ncbi.nlm.nih.gov/22801223/
https://casereports.bmj.com/content/14/1/e237690
Hashimoto's (High TSH) [B]
Enteroviruses are specifically noted to cause Hashimoto's by attacking the thyroid glands, however, there is some additional evidence pointing towards EBV, HSV (1 and 2) and HHV-6 causing this as well. Other viruses with insufficient evidence include Parvovirus B19 and Measles.
Also, this is rather a common comorbidity with ME/CFS.
https://www.boostthyroid.com/blog/2018/8/8/viruses-and-hashimotos
https://www.mdpi.com/2076-2607/9/4/876/pdf
Lastly, there is this study noting 11% had EV RNA in blood vs 0% healthy controls, which is small but still notable especially when you consider it was a much older article/study and they didn't have the testing methods for EV like we do now, like the VP1 protein stomach biopsy stain.
https://www.liebertpub.com/doi/abs/10.1089/thy.2019.0607?journalCode=thy
Grave's (Low TSH) [B]
Okay, so this is the exact opposite of what Hashimoto's is, but it's the same idea and there is far more evidence linking EV to Grave's disease than Hashimoto's...
https://pubmed.ncbi.nlm.nih.gov/23280563/
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/23280563/
Then there is some other evidence suggesting that EBV, HSV-1, Measles, Rubella, Parvovirus B19, and Retroviruses like HTLV-1 and SV40 may contribute to the development of Grave's disease.
https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-6-5
https://www.liebertpub.com/doi/10.1089/vim.2010.0072#:~:text=In Graves' disease, the IgG,lymphocytes, and is occasionally reactivated.
High IL-19 levels [P]
This is a weird one, but essentially high IL-19 can indicate TH1/TH2 imbalance and that is very significant in the development of ME/CFS.
https://pubmed.ncbi.nlm.nih.gov/22103848/
https://pubmed.ncbi.nlm.nih.gov/12370360/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276674/
Primary Billary Cholangitis [S]
Okay, so, this one is interesting because it involves the liver and the smaller little bile ducts getting slowly destroyed. There is some evidence of bacterial agents such as E. Coli and others doing this and also possible Retroviruses causing this too.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300644/
However, this next article shows that Coxsackie B4 Virus, Herpes Simplex Virus 1 (HSV-1) and Adenovirus 2 also had the potential to cause this pathology. So, the evidence is here that many pathogens can cause this, however, there isn't enough evidence in my honest opinion to make a reasonable conclusion.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166250/
So, the evidence for EVs case is quite poor, but it is clear that some sort of pathogen or even multiple pathogens can cause this disease.
Vitiligo [S]
Okay, so this is one of these cases where we have to connect the dots and 'bridge' the gaps in the research papers.
https://pubmed.ncbi.nlm.nih.gov/23382179/
So here we see that in vitiligo the NLRP1 inflammasome is incredibly important in developing this disease. Well, then we have this next article that shows EV can activate this pathway via the 3C protease that Enteroviruses have...
https://www.science.org/doi/10.1126/science.aay2002
But, there is no direct evidence yet, so it remains skeptical, but I would wager it is largely caused by Enteroviruses.
Also, there is more evidence pointing towards herpesviruses and even HIV.
https://medwinpublishers.com/VIJ/VIJ16000181.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134483/
Crohn's disease [C]
Alright, this is yet another Inflammatory Bowel Disease (IBD) like UC that is found in Chia's healthy controls that test positive in the stomach biopsy for the Enteroviral VP1 protein. And, not only that, 9 out of 9 (100%) of Crohn's disease patients were tested Colon biopsy positive for BOTH Coxsackie B Virus and Echovirus!
This 2013 study is what shows they found Enterovirus in colon and Ileum (last part of small intestine, before large intestine/colon)...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696939/
So, clearly CVB and Echo have tropism here.
However, they may have found other enteroviruses in this study as well...
They mention finding HEV, Human Enterovirus (generic) in many of the patients, but didn't talk too much about it becuse the focus of their study was to look specifically for CVB and Echo.
https://www.sciencedaily.com/releases/2013/06/130627102827.htm#:~:text=Summary:,this chronic inflammatory intestinal disorder.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828589/
And here Dr. John Chia notes that specifically Echovirus 18 is associated with Crohn's disease.
https://www.scirp.org/journal/paperinformation.aspx?paperid=94556
Celiac disease [C]
This one is a little odd, there is conflicting evidence that Adenovirus may cause this disease, but it seems there is very solid evidence that Celiac itself is caused by EV. Also, many patients report sudden gluten Intolerance that coincides with their ME/CFS onset... This isn't a coincidence, there is a clear link between Celiac and "Celiac like" diseases and EV.
https://www.sciencedaily.com/releases/2019/02/190213192455.htm#:~:text=FULL STORY-,A common intestinal virus, enterovirus, in early childhood may be,risk of later coeliac disease.
https://www.frontiersin.org/articles/10.3389/fimmu.2020.604529/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884453/
Which explains why even in the acute Enteroviral infections some develop temporary gluten intolerance that later goes away after the infection is cleared.
Myasthenia Gravis [B]
So, this one is kind of crazy because not only can Enteroviruses cause this disease but so can our good old friend EBV. But the evidence here is pretty damning so there isn't a whole lot to say, the articles speak for themselves. Remember that even if MG is caused by poliovirus, which is almost extinct at this point, it is still considered an Enterovirus! One of these also mention Rhinovirus, which is known to cause the common cold, also possibly playing a role in this disease. Rhinoviruses are also part of the Picornavirus family, so, again, Enteroviruses.
https://www.hindawi.com/journals/ad/2011/213092/
https://www.nature.com/articles/s41598-017-04993-y
https://pubmed.ncbi.nlm.nih.gov/20368632/
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [B]
Here it is, the one you all having been waiting for. So, if you haven't already I highly recommend watching this video by PolyBio, it pretty much explains the entire Enterovirus theory.
Here are some important MEpedia links as well...
https://me-pedia.org/wiki/List_of_enterovirus_infection_studies
https://me-pedia.org/wiki/Non-cytolytic_enterovirus
https://me-pedia.org/wiki/Autopsy_in_Myalgic_Encephalomyelitis
These list out all EV studies and show the importance of Non-Cytolytic Enteroviruses and why they are so critical in the pathology and development of MECFS.
Also note that 100% of brain autopsies found Enteroviral remnants in patients brains so far...
Obviously, other reasons have been proposed like herpesviruses, but as noted before, often these DNA (herpes) viruses are persisting because of the TH cell population imbalance and/or dysfunction. Chia finds almost 85% of his patients are EV positive vs 20% controls, which is significant. Other causes are structural issues, mold, and many many others. But, EV is by far the most common. And, again, I wouldn't be surprised if other ss+RNA viruses do this including COVID.
https://www.frontiersin.org/articles/10.3389/fmed.2021.688486/full#:~:text=Enteroviruses (EVs) as a cause,system, muscle, and heart.
https://pubmed.ncbi.nlm.nih.gov/8354926/
Irritable Bowel Syndrome (IBS) [C]
This one is fairly obvious. I mean, I hear over and over again the argument that these viruses are common, so why does it cause these diseases? Well, according to this article:
https://www.virology.ws/2018/12/27/...ic-nervous-system-and-intestinal-dysmotility/
Yes, 10-30% of people have IBS, that's quite a large amount and again Enteroviruses are common.
I really recommend reading that article because so many people narrow in on the Central Nervous System (CNS), but what is equally as important if not more important is the Enteric Nervous System (ENS).
IBS is also caused by Norovirus, which has been shown to become persistent and is very similar to Enteroviruses.
Also, this is yet another one of the diseases that Dr. Chia finds in his healthy controls when doing the stomach biopsy VP1 protein stain, which if 20% of controls are EV positive, that lines up with the population range we see here with IBS.
https://pubmed.ncbi.nlm.nih.gov/25431489/
https://www.seattletimes.com/life/w...go-away-it-might-be-irritable-bowel-syndrome/
https://www.researchgate.net/public...orovirus-Enterovirus_Gastroenteritis_Outbreak
https://www.genengnews.com/topics/t...r-protect-against-inflammatory-bowel-disease/
Coincidence that they consider CFS and IBS "post viral"...?
Hmmm... I think not!
Type One Diabetes (T1D) [C]
This one surprises many, but it's another very obvious one. Like, it has been proven, time and time again, that T1D is caused by Coxsackie B4 Virus. The average age of T1D onset is around the ages of 17-21 and the MECFS average age of onset is 19-23... That's not a coincidence.
https://pubmed.ncbi.nlm.nih.gov/18951821/
https://pubmed.ncbi.nlm.nih.gov/9662368/
https://www.pnas.org/doi/10.1073/pnas.0700442104
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276674/
This last article touches on why Interferon Alpha, actually makes CVB4 worse because of it's unique tropism.
Essentially, IFN alpha is ineffective for CVB4 because it inhibits IFN gamma which is important for specifically CVB4. This is why Chia finds his IFN therapy did not work on CVB4.
Acute Flaccid Myelitis [C]
Very recently has this been linked to Enteroviruses. It's often seen in children and often, again, EV is commonly contracted as a child. It is when the virus invades the CSF that you get this lovely disease. It is almost like polio... but not quite. Just note the similarities of what the CDC has to say about this illness:
https://www.cdc.gov/acute-flaccid-myelitis/index.html
https://journals.asm.org/doi/10.1128/mBio.01903-19
https://www.nih.gov/news-events/nih...virus-infection-linked-acute-flaccid-myelitis
Idiopathic Gastroparesis [C]
This is a fun one. So, in the very severe cases, the virus can infect your vagus nerve causing GP. And most "idiopathic" cases are really just EV. 9 out of 10 of idiopathic cases turned up to be EV and it seems a minor subset is also caused by your lovely neighborhood friend, Norovirus. The underlying mechanism is again, infection, likely through the CNS and/or ENS. Also, keep in mind these viruses love to travel up through the vagus nerve and use it like a highway to evade your immune system and reach places like your brain and eyes.
https://link.springer.com/article/10.1007/s10620-016-4227-x
https://pubmed.ncbi.nlm.nih.gov/27344315/
https://www.cureus.com/articles/21623-norovirus-induced-gastroparesis
Idiopathic Mast Cell Disease/Activation Syndrome [B]
Okay, so, we know mast cells are an important part of the immune system and immune defense, so if you have a chronic infection, it would make since you would also have a chronic mast cell issue, which, if you idneitfied the pathogen would actually make it secondary not idiopathic.
But, nonetheless, many viruses cause this to happen (usually acutely), but not in our case. Many pathogens also cause elevated tryptase. This is why MCAS is such a common comordbidity in us.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529115/
https://www.annallergy.org/article/S1081-1206(17)30850-5/pdf
https://www.microbiologyresearch.org/content/journal/jmmcr/10.1099/jmmcr.0.005012?crawler=true
GERD [B]
So, despite what many typically think of when they hear 'GERD' this is often, in our case, caused by low stomach acid. Which, is weird to think about at first, but seriously, think about it. A chronic viral infection such as EV will deplete your stomach acid due to the infected cells. Then, you get this reflux because there is not enough acid. But, why would PPIs help then? Well, remember, PPIs work by inhibiting the actual mechanism that our muscle in the esophagus uses and suppressed that "reaction" it is having due to, again, low stomach acid. So, by having a low amount of acid, it is essentially "gasping" for "air" (acid).
Obviously, other diseases and infections can cause this too, like H. Pylori.
https://www.enterovirusfoundation.org/the-symptoms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563291/
https://biopractica.com.au/a-nasty-little-bug-that-can-cause-heartburn-reflux/#:~:text=Helicobacter pylori, or H.,ulcers, and even stomach cancer.
Herpangina [C]
Often seen in children, this disease is similar, but distinct from HFMD. It is often caused by Coxsackie A and B virus as well as occasionally EV71A.
https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/herpangina#:~:text=Herpangina is a febrile disorder,also Overview of Enterovirus Infections
https://www.ncbi.nlm.nih.gov/books/NBK507792/
Dilated Cardiomyopathy [B]
Another disease that seems to be driven by Coxsackie B virus. I think Echovirus can also cause this as the article just mentions Enterovirus Group B, which seems to include Echoviruses.
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.035966#:~:text=Group B enteroviruses are common,of dilated cardiomyopathy remain unclear.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056497/
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
Myocarditis [B]
Another cardiovascular one. Many viruses cause this including Adenovirus, Coxsackie B, and others. However, it seems Enteroviruses are the most frequent viral form of this disease.
https://heart.bmj.com/content/83/1/86
https://fn.bmj.com/content/89/5/F461
https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-12-212
https://www.ahajournals.org/doi/10.1161/circulationaha.108.766022
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135016/
https://www.frontiersin.org/articles/10.3389/fcimb.2016.00171/full
This last one shows that Coxsackie B3 caused th17 dysregulation which is another important thing in the development and maintenance of ME/CFS.
Functional Dyspepsia [C]
This one remained a mystery up until Dr. Chia came out with a study showing that this disease is associated with Enteroviruses.
https://www.scirp.org/journal/paperinformation.aspx?paperid=55465
Chronic Gastritis [C]
Same evidence as above, again, Chia coming in and showing how people underestimate EVs potential to cause diseases.
https://www.scirp.org/journal/paperinformation.aspx?paperid=55465
Aseptic Meningitis [B]
A handful of viruses can cause this problem, but, EV is by far the most common. No other virus comes close! Enteroviruses were 25% of the cases of Aseptic Meningitis compared to it's runner-up which was HHV-6 at 7.9% of cases.
https://emedicine.medscape.com/article/1169489-overview#:~:text=Viral infection,have been linked with meningitis.
https://www.frontiersin.org/articles/10.3389/fneur.2020.602267/full
Conjunctivitis [B]
Okay, so this one is very often Enteroviruses, specifically Coxsackie A24 and Enterovirus D70 generally. But, some other pathogens do this too. Just, most notably EV.
https://www.sciencedirect.com/topics/medicine-and-dentistry/acute-hemorrhagic-conjunctivitis#:~:text=Acute hemorrhagic conjunctivitis is a,and fine, punctate epithelial keratitis.
https://www.cdc.gov/conjunctivitis/clinical.html
Myopericarditis [B]
So, this one is often related to Coxsackie B. Obviously, other causes of this one as well. Notice how most of the heart related diseases are usually Coxsackie B. It is because this virus has tropism for those cells.
https://www.ajconline.org/article/0002-9149(74)90201-X/pdf
https://pubmed.ncbi.nlm.nih.gov/11808426/
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
Pericarditis [B]
Pretty much the same evidence as above with the additional note that both Coxsackie and Echovirus cause this, but wouldn't surprise me if other EV forms did as well or other ss+RNA viruses.
https://www.spandidos-publications.com/10.3892/mmr.2014.2578
https://loinc.org/88538-4/#:~:text=Viral infections are a common,etiologies associated with viral pericarditis.
Hands Foot and Mouth Disease (HFMD) [C]
Not much to say here, besides it is common in children and often associated with Coxsackie A16 and Enterovirus 71A.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873753/
Encephalitis [B]
Pretty common severe acute symptom of infection. Many viruses can cause this, most notably herpes and enteroviruses, but certainly aren't just limited to these. I only included it because some people still deny it can penetrate the CNS.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044131/
https://www.mountsinai.org/health-library/report/viral-encephalitis#:~:text=These viruses include the herpes,most common cause of encephalitis.
https://www.frontiersin.org/articles/10.3389/fmicb.2020.00261/full
Paralysis [C]
I only put this down as solely Enterovirus because it is by far the most associated with this complication, like, no other virus comes close. Specifically, EV D68. And I really couldn't find any other cases of herpes or other exotic ss+RNA viruses doing anything similar. Polio also falls under this.
https://www.statnews.com/2019/06/14/acute-flaccid-myelitis-possible-cause-paralysis-kids/
https://www.frontiersin.org/articles/10.3389/fneur.2017.00638/full
Epididymitis [B]
Believe it or not, this is very often "post" infectious. Like, many cases of these are after acute infection. Which one would not think right away, as the testicles are an "immuno-privileged" site. Well, this is not always the case. I mean, there is even a case of a guy who survived EBOLA VIRUS who ended up transmitting the virus to someone sexually after FIVE YEARS which actually TRIGGERED A NEW OUTBREAK!
So, this is a broad disease, caused by many infections, but with Enteroviruses it seems to be Coxsackie Type A Virus most notably. I am sure COVID and other EVs and even any other forms of ss+RNA viruses can cause this annoying symptom/disease. Many with ME/CFS including myself note this symptom only pops up following exertion.
https://publications.aap.org/aapgra...7/87518/Epididymitis-is-Often-Post-Infectious
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313299/
https://www.livescience.com/ebola-lingered-survivor-sparked-outbreak.html
Poliomyelitis [C]
Yes, the three types of poliovirus are indeed Enteroviruses. According to the CDC about 0.5% to 1% of cases will actually go on to develop poliomyelitis... Again, I often here the argument that EV is common so why only a small percentage get ME/CFS? Well, that is like saying back in the 1900s that Poliovirus is common and why do only a select few get chronic poliomyelitis and paralysis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212416/
https://www.cdc.gov/polio/what-is-polio/index.htm
Hepatitis A [C]
This is another one that shocks many. So, early on this was initially classified as an Enterovirus 72, however, once they learned that other viruses caused Hepatitis it was later renamed to Hepatitis A. But, the fact still remains, this is an Enterovirus.
https://www.karger.com/Article/Pdf/149313
https://www.news-medical.net/life-sciences/Enterovirus-72-Infection.aspx
And recently, like, currently there is a Hepatitis A outbreak. Thankfully most everyone is vaccinated against it already.
https://www.clickondetroit.com/cons...-sold-at-kroger-walmart-other-grocery-stores/
Sjorgen's Syndrome [C]
Seems like EV has the most confirmed papers on this so far, most notably Coxsackie B4. Some minor indication retroviruses may play a role but not nearly enough evidence.
https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.20463
https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1313.090
https://www.robertfoxmd.com/SjogrensByFox/Sjogren's_syndrome-Infections_that_Mimic.pdf
Eosinophilic Esophagitis (EoE) [B]
EoE is a common comordbidity of MCAS and can be due to infection or primary MCAS and other diseases.
EoE can be driven by infection and so can MCAS. So, both can be primary or secondary. Eosinophils in blood usually don't represent what's in the tissues, so keep that in mind.
I strongly believe if you have ME/CFS and you have EoE, there is a solid chance that you have it caused by an infection.
Picornavirus Infection of Esophageal Epithelial Cells (Picornavirus is a family of viruses that include Enterovirus, Rhinovirus, etc.) can cause EoE.
https://www.jacionline.org/article/S0091-6749(19)32469-8/fulltext
This article explains how this infection is also in epithelial cells, in the esophagus. And that it expresses the IFNL1 receptor. This is for IFN-Lambda1, so Peginterferon Lambda 1a is effective on these receptors. And is the ONLY interferon that would work.
https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=134&ContentID=169
Iron Deficiency / Anemia [P]
Alright, so... Many viruses, in fact, most viruses will deplete your iron either by infecting the cells or inhibting the ability to functionally use that iron. And believe it or not, viruses rely on iron to survive.
https://www.sciencedirect.com/science/article/pii/S0098299720300224
https://jmhg.springeropen.com/articles/10.1186/s43042-020-00114-z
Dr. Chia also notes that many of his chronic EV patients become iron deficient.
https://www.enterovirusfoundation.org/the-symptoms
Pleurodynia [C]
This type of chest pain seems to go in epidemics following Coxsackie A and B Virus as well as Echovirus. So, it seems like basically all EVs can do this.
https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/epidemic-pleurodynia#:~:text=Epidemic pleurodynia is a febrile,is most common among children.
https://www.verywellhealth.com/pleurodynia-overview-4171796
Hypoxia / Low Blood Oxygen Levels [B]
Obviously a lot of things can cause this problem, but specifically Enteroviruses A71 and D68 are noted the cause this more than other EVs. Bacteria, parasites, and other viruses can also do this.
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0585-y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004002/
Fibromyalgia [B]
So, pretty much like ME/CFS, EBV and other viruses including Enteroviruses can cause this and research is now showing it is considered "post infectious".
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/14556267/
https://me-pedia.org/wiki/Fibromyalgia_notable_studies
Alzheimer's [S]
I only found one article, showing that broad-spectrum antiviral therapy and a specific medication, Pleconaril, which is active on EVs, improved some patients Alzheimer's. However, this is the only study, and I am sure other studies are floating around out there with other infectious agents or other theories in general. So, while I think this is a good start, it isn't enough to come to a sensible conclusion.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203284/
And... case in point! Here we have some evidence of bacterial agents, HSV-1, HHV-6, and HHV-7 (Herpesviruses) possibly playing a role here as well...
https://www.nature.com/articles/d41586-020-03084-9
Dementia [B]
While many of us may feel like we have dementia, Enteroviruses have been proven to cause rapid progressive dementia in a 28-year old...
https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/26727905/
Of course, other pathogens like bacteria have been shown to possibly cause this as well.
https://www.frontiersin.org/researc...nships-between-infectious-agents-and-dementia
Reactivated / Persistent Herpes [C]
Alright, so, herpesviruses can reactivate for a lot of reasons like 'trauma', however, many of these stress cases actually just weaken the immune system leading to the virus seeing an opportunity. And in COVID and EVs cases, we see that it will reactivate due to these infections causing TH1/TH2 imbalance and now your immune system can not handle the virus naturally and it will persist until that dysfunction is fixed (i.e. getting rid of the persistent COVID or EV).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809354/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330347/
https://link.springer.com/article/10.1007/s00415-020-10265-z
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233978/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959425/
GPCR Auto Antibodies (CellTrend) [S]
Okay, so this is yet another one where we have to connect the dots. This will show the importance of the Enteric Nervous System (ENS).
It has to do with the fact that these neurotransmitters are in our gut lining, in the enteric nervous system and that damage here to cells, neurons and these neurotransmitters from Enterovirus, ends up creating these autoantibodies.
https://journals.physiology.org/doi/full/10.1152/ajpgi.00406.2018
We already know EV infects the neurons and cells in these areas. So we already can strongly theorize that when EV infects cells, it can create auto-antibodies to those cells, as well as the expressions on the surface of those cells (e.g. TS-HDS).
Then you have this, which shows that the ENS and CNS are almost identical!
https://en.wikipedia.org/wiki/Enteric_nervous_system
So, if the neurotransmitters are identical, then with reduced self-tolerance, the gut-brain-axis connection makes it EASY for there to be autoantibodies to these neurotransmitters in the BRAIN as well!
Which, the cause of this is all from the infection in the ENS.
However, there is no direct evidence, but I believe what has been shown here is very strong.
Small Fiber Neuropathy (SFN) [B]
Many viruses can cause autoimmune SFN (TS-HDS and FGFR3 aabs), including Enteroviruses and COVID. Usually this form of SFN is mild or borderline positive.
https://pubmed.ncbi.nlm.nih.gov/1322452/
https://pubmed.ncbi.nlm.nih.gov/34766365/
PEM [P]
Would you look at that, it's our favorite symptom! Okay, so, a lot of mitochondrial diseases and other genetic issues can cause this problem, heck, even chemotherapy people are noted to have PEM. However, many viruses are made much worse upon exertion, most notably Enterovirus, EBV, Norovirus, Rotavirus, HIV/AIDS and Parvovirus B19. So, most of these are ss+RNA viruses again and the reason I think that is is because of the ERK1 receptor.
So ERK1 is involved in viral replication and ERK1 is also activated by exercise...
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2005.103481
A lot of viruses infections including ebv, Enteroviruses, rotavirus, norovirus, and COVID (most of which are all RNA) get worse based on the above mechanism.
This makes sense.
A chronic viral infection means that any dopaminergic upregulation will be met with viral insult. It basically conditions the arousal system towards a hypoactive state by sheer immune punishment.
Growth and differentiation pathways enhance metabolic allocation to a cell, viruses depend on this metabolic allocation to replicate using the cell's machinery... So a global increase in growth and differentation activity triggered by physical or mental exertion would be an accessory to viral activity.
Also, dopamine is an important immunomodulator and it makes sense that viruses would use Dopamine Receptors (DRs) as part of their invasive schema... And many of us feel better on dopamine drugs like pregablin, abilify, many others...
https://pubmed.ncbi.nlm.nih.gov/2483440/
This shows that many patients have low aldosterone and dopamine. And according to CellTrend, almost 50% of patients have autoantibodies that antagonize the function (not level) of Angiotensin II, which would ALSO deplete your aldosterone, since Angiotensin II is what helps regulate and produce your aldosterone.
I know many cases, including myself, who have UNMEASURABLE aldosterone. Like, there was not a drop of it detected.
This both contributes to POTS and OI indirectly and directly.
And here, it looks like dopaminergic hyperactivity tends to increase viral replication with HIV, as well.
https://www.sciencedirect.com/science/article/pii/S0002944010606244
Finally, here is a brief overview of excerise exacerbating respiratory infections in general (this includes Enteroviruses)...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803113/
CONCLUSION:
Enteroviruses are by FAR the leading virus associated with diseases. Like, no other virus even comes close. Herpesviruses, the list I have for them dwarves in comparison to this, only about half. And COVID we don't know everything yet but it's trailing behind Herpesviruses from what I have seen and gathered thus far. So, yeah, they may be common, but there are also so many complications associated with them. There is a total of 52! Think about that...
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