Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation, 2021, Gold et al

Peter T

Senior Member (Voting Rights)
An interesting article on a possible association between Long Covid and EBV reactivation, thank you Anil (sorry forgotten your user name here) for alerting me to this on Facebook:

Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation
Gold et al
Pathogens 2021, 10(6), 763
https://www.mdpi.com/2076-0817/10/6/763

Abstract
Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein–Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p < 0.001, Fisher’s exact test). A similar ratio was observed in a secondary group of 18 subjects 21–90 days after testing positive for COVID-19, indicating reactivation may occur soon after or concurrently with COVID-19 infection. These findings suggest that many long COVID symptoms may not be a direct result of the SARS-CoV-2 virus but may be the result of COVID-19 inflammation-induced EBV reactivation.

[added - sorry if this has been posted as part of an existing thread, I tried to look but struggle searching for things]
 
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An article in Medicalxpress about this paper

Long COVID symptoms likely caused by Epstein-Barr virus reactivation
https://medicalxpress.com/news/2021-06-covid-symptoms-epstein-barr-virus-reactivation.amp

Epstein-Barr virus (EBV) reactivation resulting from the inflammatory response to coronavirus infection may be the cause of previously unexplained long COVID symptoms—such as fatigue, brain fog, and rashes—that occur in approximately 30% of patients after recovery from initial COVID-19 infection. The first evidence linking EBV reactivation to long COVID, as well as an analysis of long COVID prevalence, is outlined in a new long COVID study published in the journal Pathogens.

"We ran EBV antibody tests on recovered COVID-19 patients, comparing EBV reactivation rates of those with long COVID symptoms to those without long COVID symptoms," said lead study author Jeffrey E. Gold of World Organization. "The majority of those with long COVID symptoms were positive for EBV reactivation, yet only 10% of controls indicated reactivation."

[corrected typo]
 
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The numbers in this retrospective study seem to me quite small.

Also though there would appear to be an association between Long Covid and EBV reactivation, there are some subjects with EBV reactivation and no Long Covid and some with Long Covid but no EBV reactivation, suggesting that EBV reactivation is neither necessary nor sufficient to explain Long Covid fully without additional variables being taken into account.

The paper does not seem to address the heterogeneity of Long Covid which could be significant in relation to any impact of EBV reactivation, and surprisingly makes no mention of ME/CFS despite the relatively high association between active EBV infection (ie glandular fever/mononucleosis) and developing ME/CFS.

[added - I am also left wanting to know more about EBV reactivation in relation to other viruses, but their introduction was unclear if much is known about this.]
 
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[added - I am also left wanting to know more about EBV reactivation in relation to other viruses, but their introduction was unclear if much is known about this.]

This is what I found on Wikipedia:

Latent EBV in B cells can be reactivated to switch to lytic replication. This is known to happen in vivo, but what triggers it is not known precisely. In vitro, latent EBV in B cells can be reactivated by stimulating the B cell receptor, so reactivation in vivo probably takes place when latently infected B cells respond to unrelated infections.[21] In vitro, latent EBV in B cells can also be reactivated by treating the cells with sodium butyrate or 12-O-Tetradecanoylphorbol-13-acetate.[citation needed]​

So not much but it looks like this is not unique to covid. But I guess reactivation during an infection and reactivation also during long covid may be two different things.

My n=1 story: I believe I got my EBV infection from someone with reactivated EBV during an infection. He was someone I dated and he had a very bad viral throat infection for weeks, which I also caught from him. Then a while later I developed mononucleosis (EBV has a much longer incubation period, hence the delay). The timing made sense and also, EBV is actually not so easy to catch, so my guess is this is how it probably happened.
 
I would be pretty sceptical about claims about reactivation of EBV based on antibody tests. This is an issue that has been knocking around for decades and I think the conclusion has been that individual early antigen or IgM test results tell us little. I think to be convincing we would need to know what the titres for these people were before Covid. Maybe they are just people with higher titres. There is also the anamnestic effect of antibodies to other microbes rising non-specifically after a new infection.

True reactivation of EBV can occur in immunosuppressed people although it is not that common even there. We all carry EBV pretty much and I think the reactivation story is mostly sloppy medicine associated with fringe physicians overinterpreting tests that have a wide variation normally.
 
There is also the anamnestic effect of antibodies to other microbes rising non-specifically after a new infection.
I'm continuously grateful for your presence here and all the knowledge you share.
I didn't know this, but I guess it makes sense..

Last year I spoke to a neighbour who had recently undergone Covid-19. She was recovering, but said she had been told by her doctor that she had a reactivation of borrelia. Same day I spoke to a friend who has a sister who also was recovering from Covid-19 and had gotten the same message about having a reactivation of borrelia. I thought it was curious, but from what you are saying, this just might be expected following an infection.
 
My n=1 suspicion. It's possible that I contracted Covid early last year before the WHO declared the pandemic. I've mentioned my vestibular virus several times here so not going to bore everyone, but I'm still dealing with it over one year later.

I have never experienced this type of sickening virus and the manner in which it has taken on a whole life of its own with bizarre symptoms in the 30 years of having ME,

I've had many reactivations of herpes viruses in the last 20yrs, but not like this one.
 
My n=1 suspicion. It's possible that I contracted Covid early last year before the WHO declared the pandemic. I've mentioned my vestibular virus several times here so not going to bore everyone, but I'm still dealing with it over one year later.

I have never experienced this type of sickening virus and the manner in which it has taken on a whole life of its own with bizarre symptoms in the 30 years of having ME,

I had similar symptoms from late March last year, my labyrinthitis took about 6 months to recover, I still have some ear blockage issues. It also infected my mouth, causing significant gum recession and I still have strange mouth/gum pain. I'm not sure this was due to COVID though.
 
Ditto. I have fever blisters on my tongue and lips this week. I've also been having fluid buildup in my right ear and sinuses, and it's not allergy related. When I hold my nose to try to deblock, I hear this load sweak coming from my R ear.
 
I would be pretty sceptical about claims about reactivation of EBV based on antibody tests. This is an issue that has been knocking around for decades and I think the conclusion has been that individual early antigen or IgM test results tell us little. I think to be convincing we would need to know what the titres for these people were before Covid. Maybe they are just people with higher titres. There is also the anamnestic effect of antibodies to other microbes rising non-specifically after a new infection.

True reactivation of EBV can occur in immunosuppressed people although it is not that common even there. We all carry EBV pretty much and I think the reactivation story is mostly sloppy medicine associated with fringe physicians overinterpreting tests that have a wide variation normally.
I would assume Leonard Jason's study could answer that question? Rare opportunity to benefit from a prospective study here.
 
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