Negative IgM means no active infection?

[MarkRichardson]

I’m a bit confused. Does having a negative IgM on a blood test for a virus usually rule out an active viral infection?

For instance on my EBV blood test I have positive IgG, negative IgM and positive Lytic antigens (T-Cells).

I’ve spoken to four different doctors about this, three of them being ME specialists and have received different opinions as to wether I have an active EBV infection or not.

So far I’ve been told that if IgM is not positive then there is no active infection, that IgM is only positive for a few weeks/months after the virus is first active, Lytic antigens suggest that the virus is replicating, IgM normal result suggests the virus is contained within cells and is not in the bloodstream, my results show that I am having an immune response to a non active (past?) infection.

Hidden viral reservoirs are something I’ve heard about, I am not sure wether this means infections are active or not, or wether inactive viruses will respond to antivirals?

I’m aware that some people with immunological issues can’t test positive on certain tests for viruses but as far as I understand it that is not the norm.

I see some ME patients take antivirals, is that in the belief there is an active infection? Regardless or not of wether they have a positive IgM?

Now I will say that I am scientifically illiterate so what I am saying may be well misunderstood and confused, apologies for that.

 

[DrUniverse]

No, you can have an active Infection without positive igm.

that IgM is only positive for a few weeks/months after the virus is first active

But that is true yes. Only positive in first Infection

 

[Judee]

Plus, many of us here are IgM deficient. I was told by one doctor that he wasn't sure but thought maybe that would affect my test results. When I emailed a lab about it, they said the same thing.

Have you been tested for IgM deficiency?

 

[wabi-sabi]

I’ve spoken to four different doctors about this, three of them being ME specialists and have received different opinions as to wether I have an active EBV infection or not.

I think this speaks to the difficulty of figuring out EBV infections.

EBV, like chicken pox, is in the herpes virus family. Once you've caught one of them, they stay in your body forever. In general, viruses have a primary active infection stage, a latent stage, and a reactivation or lytic phase.
So, if you think of chicken pox, you have the primary active infection when you are little and then some years later when you are elderly you get shingles, which is the reactivation. In between, the latent phase, you feel just fine because the virus is in hiding.

Now with EBV, the latent phase doesn't mean the virus is doing nothing. It's very carefully hiding from the immune system and making sure that its genes are passed on whenever a cell divides. Latent just means it's not actively making new virus and killing your cells in the process. There are 5 different ways an EBV can hide from the immune system, and the science is pretty deep going.

Trouble is, there doesn't seem to be anyway to get latent viruses out of your system. Antivirals stop viruses from replicating. Latent viruses are hiding, not replicating, so no dice there. This may or may not be why some PwME benefit from antivirals and which don't.

Given all this uncertainty, you might ask your doc what they think the pros and cons of taking an antiviral would be for you. Then you can think about whether you want to try that treatment or not. Just keep in mind, no matter how many antivirals you take, that EBV is never going to leave your system.

 

[wabi-sabi]

From Gulley, M. L., & Tang, W. (2008). Laboratory assays for Epstein-Barr virus-related disease. The Journal of molecular diagnostics : JMD, 10(4), 279–292. https://doi.org/10.2353/jmoldx.2008.080023

 

[heapsreal]

Just keep in mind, no matter how many antivirals you take, that EBV is never going to leave your system.

I will just add my 10 cents. If one can get their viral load down with antivirals they can feel better. For some once they get the viral load low enough, then their immune system is capable of managing it and keeping the viral load low

 

[heapsreal]

I’m a bit confused. Does having a negative IgM on a blood test for a virus usually rule out an active viral infection?

For instance on my EBV blood test I have positive IgG, negative IgM and positive Lytic antigens (T-Cells).

I’ve spoken to four different doctors about this, three of them being ME specialists and have received different opinions as to wether I have an active EBV infection or not.

So far I’ve been told that if IgM is not positive then there is no active infection, that IgM is only positive for a few weeks/months after the virus is first active, Lytic antigens suggest that the virus is replicating, IgM normal result suggests the virus is contained within cells and is not in the bloodstream, my results show that I am having an immune response to a non active (past?) infection.

Hidden viral reservoirs are something I’ve heard about, I am not sure wether this means infections are active or not, or wether inactive viruses will respond to antivirals?

I’m aware that some people with immunological issues can’t test positive on certain tests for viruses but as far as I understand it that is not the norm.

I see some ME patients take antivirals, is that in the belief there is an active infection? Regardless or not of wether they have a positive IgM?

Now I will say that I am scientifically illiterate so what I am saying may be well misunderstood and confused, apologies for that.

Also take into account immune markers that are non specific eg neutrophils lymphocytes, T cell subsets. They can show your immune system is fighting something, then it's an educated guess for which infections. If you have access to viral titres and your ebv igg titres are really high and a non specific marker is high, then you could lean heavily towards ebv reactivating.

 

[wabi-sabi]

If one can get their viral load down with antivirals they can feel better.

Yes, this is true. But we still need the info on whether it's a high viral load or the body's response to the virus or something else entirely.

That's part of the issue with the difficulty in figuring out if there's a viral reactivation or not.

 

[heapsreal]

Yes, this is true. But we still need the info on whether it's a high viral load or the body's response to the virus or something else entirely.

That's part of the issue with the difficulty in figuring out if there's a viral reactivation or not.

One way to find out is to treat the virus and see what happens I guess. A 3 month treatment trial could give some answers. Co-infections may blur the results. Dr Lerner use to find those with ebv that didn't respond to antivirals, alot of the time also had a chronic bacterial infection eg mycoplasma, lyme etc which can also be hard to diagnose too.

 

[MarkRichardson]

One way to find out is to treat the virus and see what happens I guess. A 3 month treatment trial could give some answers. Co-infections may blur the results. Dr Lerner use to find those with ebv that didn't respond to antivirals, alot of the time also had a chronic bacterial infection eg mycoplasma, lyme etc which can also be hard to diagnose too.

I took a course of ivermectin that I didn’t respond to, now depending wether you think ivermectin can work as an antiviral to EBV or not may indicate what you are saying it could, or not. Is it that co-infection stop antivirals working or that the benefit of them is not felt until all infections are treated?

 

[wabi-sabi]

antivirals working or that the benefit of them is not felt until all infections are treated?

I don't know about multiple infections at the same time. But we do need to clarify what you mean when you want an antiviral to work...

The thing with antivirals is that they only stop viruses from reproducing/replicating. As long as the virus stays in hiding (latent), the antiviral does nothing to them.

Or think of it humorously like this: Antivirals stop viruses from having babies. They don't don't do anything when the virus in hanging out in our cells with its feet up watching TV or doing anything else that viruses like to do.

That means antivirals cannot eradicate an infection. Once you have EBV, you have it for life. You can force the virus to be celibate, but its very much still alive.

Will an antiviral kill all the virus and make your infection go away? no

Will the antiviral make your infection undetectable? unclear, since we don't usually test for the presence of EBV itself

Will the antiviral make you feel better? that seems to be very individual. talk to your doc!

 

[wabi-sabi]

This is an interesting article on measuring EBV. Seems to me that we can't even accurately measure EBV viral load.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379266/

Kimura, H., & Kwong, Y. L. (2019). EBV Viral Loads in Diagnosis, Monitoring, and Response Assessment. Frontiers in oncology, 9, 62. https://doi.org/10.3389/fonc.2019.00062

 

[sometexan84]

It's (usually) an active EBV infection if either the IgM is positive, OR the EA (Early Antigen) IgG.

If VCA IgM is normal... but you have high EA IgG, this is usually an active, RE-activated infection. Many of us w/ ME/CFS as well as Long Covid folks have this reactivated active EBV infection.

Should be a bunch of posts in here that go over this in more detail. I recall posting a great video that explained the interpretation of EBV results really well.

 

[Learner1]

FYI - note the charts discuss immunocompetent people, not patients who are immunodeficient in sone way. For ambiguous results, doing a PCR might be wise.

 

[heapsreal]

I took a course of ivermectin that I didn’t respond to, now depending wether you think ivermectin can work as an antiviral to EBV or not may indicate what you are saying it could, or not. Is it that co-infection stop antivirals working or that the benefit of them is not felt until all infections are treated?

I can't say I've heard ivermectin being used for herpes virus, it may but I don't know. I've heard it used for lyme disease. I'd probably go for something that has more proof or use for herpes viruses, if that's what you're going after.

I think technology is too far behind to really tell us much about chronic infections unless they are extremely overt. The last 20yrs it's really been take an educated guess and throw something at it and see if it sticks.

I can't recall the researchers name but he was saying in the 1990s the longer pts have cfs the more chronic infections they see. I guess it gets to a point that it overpowers our immune system and opportunistic infections that are normally controlled by our immune system aren't anymore. So it's possible to effectively be treating one infection but not notice much from it because of other infections. I believe this can happen alot in lyme disease treating the different bacteria.

The chicken or the egg saying in cfsme terms, the infection or the immune system.
I'm all for trying things, because if we wait for research it will be too late for this current generation.

We need one big pill that treats everything lol.

 

[heapsreal]

The thing with antivirals is that they only stop viruses from reproducing/replicating. As long as the virus stays in hiding (latent), the antiviral does nothing to them.

Or think of it humorously like this: Antivirals stop viruses from having babies.

I like the anology of stopping the viruses having babies. Antivirals maybe renamed as viral contraceptives.

I think there's also a difference between reactivating and replicating. Reactivating, the virus can be active sucking the life out of us and antivirals don't do much here either. But while reactivating is when they can get hot and bothered and replicate which is when the antivirals work.

I'm not sure Dr Lerner had evidence of this but I recall him saying for some, if on antivirals long enough, the virus can eventually burn themselves out, dying of old age maybe?? But he also said there are those that will have to stay on antivirals forever to maintain their improvements.

There was the theory of B cells being a reservoir for ebv and maybe rituximab along with antivirals, might be as close as we can get to clearing the virus from the body. Maybe add ampligen to make sure, while I'm still dreaming about cures lol.

 

[Learner1]

So it's possible to effectively be treating one infection but not notice much from it because of other infections.

Exactly. I had 5 active viral infections and 2 atypical pneumonias with my immune system going downhill. It took multiple drugs for many months to beat them all back. Valcyte, at 1.8g a day, did start to help within a month, and it is effective against 3 of the infections.

There was the theory of B cells being a reservoir for ebv and maybe rituximab along with antivirals, might be as close as we can get to clearing the virus from the body.

That is correct.. These infections also caused multiple kinds of autoimmunity, so after we beat them all back with the antivirals, antibiotics, and IVIG, I was on Rituximab for 9 months, and I haven't seen EBV since. I do suspect that killing off the B cells killed and off the EBV. The other viruses hang out in other places, so I still have problems with two of them From time to time.

 

[heapsreal]

Exactly. I had 5 active viral infections and 2 atypical pneumonias with my immune system going downhill. It took multiple drugs for many months to beat them all back. Valcyte, at 1.8g a day, did start to help within a month, and it is effective against 3 of the infections.

That is correct.. These infections also caused multiple kinds of autoimmunity, so after we beat them all back with the antivirals, antibiotics, and IVIG, I was on Rituximab for 9 months, and I haven't seen EBV since. I do suspect that killing off the B cells killed and off the EBV. The other viruses hang out in other places, so I still have problems with two of them From time to time.

That's great, Id love to try all that but that sort of forward thinking doesn't come from Australian drs. Cmv I believe hangs out everywhere.

 

[Learner1]

That's great, Id love to try all that but that sort of forward thinking doesn't come from Australian drs. Cmv I believe hangs out everywhere.

CMV hangs out in bone marrow and can lead to leukemia or lymphoma. Well worth treating.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464470/

https://www.cancernetwork.com/view/cytomegalovirus-linked-childhood-leukemia-risk

https://www.sciencedirect.com/science/article/pii/S0006497121042324

https://www.frontiersin.org/articles/10.3389/fimmu.2021.703256/full

 

[wabi-sabi]

I think there's also a difference between reactivating and replicating.

Oops, no. I don't mean to be snotty here, but reactivation and replication are exactly the same thing.

Reactivation is the mechanism whereby a latent virus that has infected a host cell switches to a lytic stage, undergoing productive viral replication and allowing the virus to spread.

Virus reactivation: a panoramic view in human infections - NCBI

The issue is that even when a virus isn't replicating/reactivating , it's still quite busy inside your cells. Remember, it's doing its whole life, except for making babies.

Under normal circumstances, a latent, non-replicating virus, doesn't cause people any problems. Does it for us? maybe. Or maybe our immune systems are reacting abnormally to a latent virus.

Hopefully people like Dr. Prusty who are virus experts, will figure this out soon.