I’m having discussions with some people who say it is possible to have viral reactivation of viruses, especially herpes family viruses like EBV, even if you have PCR tests that show no detectable viral DNA. They believe that the viral reactivation is reflected by high levels of IgG and IgM antibodies to the virus. I’m more in the camp that believes that the high Ig levels might just be residual from the initial infection. Does anyone have any idea about this?
-
New Forum Software Installed (Still a few issues but reopening the forum) More details.
Can you have “viral reactivation” if you have a negative PCR test for viral DNA?
- Thread starter Jaybee00
- Start date
Re-reading JE’s post in this thread https://www.s4me.info/threads/epstein-barr-virus-ebv-testing-pcr-versus-serology.44896/
it seems like it is possible to just miss the virus reactivation event if you aren’t doing the PCR test like everyday. I wonder if there is an actual reactivation event, for how many days will the PCR test detect virus DNA? A day, a week, a month?
it seems like it is possible to just miss the virus reactivation event if you aren’t doing the PCR test like everyday. I wonder if there is an actual reactivation event, for how many days will the PCR test detect virus DNA? A day, a week, a month?
Jonathan Edwards
Senior Member (Voting Rights)
It must be possible to have local replication of virus and miss it with blood PCR but it starts to become semantic whether this counts as a 'reactivation'.
In general I think the idea that serological levels of IgG or IgM can tell you there is reactivation when PCR is negative is just bad medicine likely promoted by fringe specialists. If there is a doubling in IgM and/or IgG levels in a specific window of time, like two weeks, that may be significant, but I would only take it seriously if the two samples had been deliberately taken as a pair and run on the same assay. Otherwise it might be a fluctuation in assay conditions.
I do not see any mileage in any of this. It is pretty much entirely driven by memes spread by private physicians who don't really understand immunology or virology. Some patients like it as an explanation but at best it is something that provides information about populations. Applicat5ion to individual people's illness is unlikely to be meaningful.
In general I think the idea that serological levels of IgG or IgM can tell you there is reactivation when PCR is negative is just bad medicine likely promoted by fringe specialists. If there is a doubling in IgM and/or IgG levels in a specific window of time, like two weeks, that may be significant, but I would only take it seriously if the two samples had been deliberately taken as a pair and run on the same assay. Otherwise it might be a fluctuation in assay conditions.
I do not see any mileage in any of this. It is pretty much entirely driven by memes spread by private physicians who don't really understand immunology or virology. Some patients like it as an explanation but at best it is something that provides information about populations. Applicat5ion to individual people's illness is unlikely to be meaningful.
wigglethemouse
Senior Member (Voting Rights)
Two studies come to mind.
1. Prusty found you can have viral proteins without replication that could cause an immune response. For HHV6A he studied U40 (a small non coding RNA I think) as a marker for latent reactivation. He then showed how that can affect model cells in the lab.
2. Jackie Cliff team found HHV6B in saliva with digital droplet PCR correlated with ME/CFS severity or was it disease state. So you might not find HHV6B PCR positive in blood, but it could be present in Saliva for example.
You would also have to take in clinical signs into the equation such as HSV1 sores.
1. Prusty found you can have viral proteins without replication that could cause an immune response. For HHV6A he studied U40 (a small non coding RNA I think) as a marker for latent reactivation. He then showed how that can affect model cells in the lab.
2. Jackie Cliff team found HHV6B in saliva with digital droplet PCR correlated with ME/CFS severity or was it disease state. So you might not find HHV6B PCR positive in blood, but it could be present in Saliva for example.
You would also have to take in clinical signs into the equation such as HSV1 sores.
jnmaciuch
Senior Member (Voting Rights)
There’s evidence in HIV that there is local low-level viral reactivation in the tissue where anti-virals don’t reach very well (it’s well documented in the brain, and is correlated with neurological symptoms) even when viral DNA is undetectable in the blood.
Though in the case of HIV-associated neurological disease, you do also have pretty clear signs of an immune response detectible in cerebrospinal fluid.
EBV is known to harbor in epithelial cells in the latency so it wouldn’t surprise me if it was possible to get transient viremia in these tissues. Especially since other infections and even various metabolic changes can knock EBV out of latency.
But it would probably have to stay at low levels locally to not be detectable in the blood, and this state is usually called viremia rather than re activation—a semantic distinction like @Jonathan Edwards notes. And I agree that Ig would be an unreliable marker except under very specific circumstances
Though in the case of HIV-associated neurological disease, you do also have pretty clear signs of an immune response detectible in cerebrospinal fluid.
EBV is known to harbor in epithelial cells in the latency so it wouldn’t surprise me if it was possible to get transient viremia in these tissues. Especially since other infections and even various metabolic changes can knock EBV out of latency.
But it would probably have to stay at low levels locally to not be detectable in the blood, and this state is usually called viremia rather than re activation—a semantic distinction like @Jonathan Edwards notes. And I agree that Ig would be an unreliable marker except under very specific circumstances
If you have these, then it's obvious something viral is going on no matter what the PCR tests say. There isn't much point in doing a fancy blood test if you have an obvious HSV sore. A clinical diagnosis is sufficient. And I've never heard an ME/CFS specialist say herpes sores have any significance for us. Otherwise healthy people can have cold sores when they get stressed, so not much specific info for us.
I think the issue is how we test for hidden viruses and when the clinical signs are ambiguous or nonspecific, like say fatigue. The question of whether or not long COVID people still have lingering virus, or even just viral particles doesn't seem to be pinned down yet, so it seems to me very unlikely if we'll get an answer about people who have had ME for longer years.
And even if we do have lingering viruses, I am very much in the dark about whether that matters. I mean most of us have had chicken pox when we were little... but what makes someone get shingles later on and someone else not?