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Epstein-Barr virus reactivation is not causative for post-COVID-19-syndrome in individuals with asymptomatic or mild SARS-CoV-2 disease course

SWAlexander

Senior Member
Messages
1,945

Abstract​

Purpose​

Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS.

Methods​

The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed.

Results​

Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups.

Conclusion​

Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08820-w
 

Murph

:)
Messages
1,799
This looks like a good study; It could save a lot of effort.

If EBV activation in long covid (and mecfs) is just by-the-by, something that happens when you're sick rather than a cause then we should stop looking at it. We can focus money and effort elsewhere.

Avindra Nath at NIH was doing an interview a couple of days ago about their big intramural study and he said specifically that - their results suggest EBV activation is a side-effect, not a cause. I was skeptical fo that,. But this study suggests he may be right.

We have too many alleyways being explored. We need to increase our confidence some of them are dead ends. This could help do that!

edit: just read the link and this study is too small to make good conclusions; what's more they included the loss of taste and smell kind of long covid in with the mecfs kind. shoddy work.
 
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cfs since 1998

Senior Member
Messages
630
would this apply to latent viruses? Or whatever we call the viruses hiding out in tissue and not reproducing yet making trouble?
I think there is enough research to suggest that EBV reactivation can occur in tissues without showing up in blood. The study design is too simplistic. I would like to see more studies measuring the latent EBV load in B-cells like this one: https://pubmed.ncbi.nlm.nih.gov/19740997/
 
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Dude

Senior Member
Messages
190
NeuroStingl on twitter: A study I was involved in had similar results - but here the EBV PCR from saliva was positive in 50% ➡️
https://onlinelibrary.wiley.com/doi/10.1111/all.15471

Our control group were people where C19 had healed without any problems. Here, 20% had a positive EBV PCR in saliva.

There were also studies on ME/CFS, where the determination of antibodies from saliva, for example, was more informative than from blood.
 
Messages
73
I know I'm only one person, but oddly, I have no EBV antibodies. I've never had it, it can't have reactivated (though I do have HHV6 antibodies). And I have a classic case of ME/CFS in terms of onset, presentation and progression (to the extent that there is such a thing). For this reason, I don't think EBV causes ME/CFS, the side effect hypothesis seems more likely.
 

Wishful

Senior Member
Messages
5,751
Location
Alberta
For this reason, I don't think EBV causes ME/CFS, the side effect hypothesis seems more likely.
The ME community should maintain a list of rare cases that disprove theories. It's remotely possible that some such cases are due to unusual situations that don't 100% disprove a theory, but it's not like there's a shortage of other theories to fund. Rich D's case should put the EBV theories down to the bottom of the list for funding. I think the abrupt temporary remissions should put down many other theories that would not result in such abrupt changes in symptoms. There are probably some other cases that similarly disprove or at least make less plausible some theories that people are asking for funding.