The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome 2023 Rasa-Dzelzkaleja et al

Abstract

Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors.

The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS.

Methods
200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines.

Results
HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients.

Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active–45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively.

ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS.

Conclusions
Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity.

Open access, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03887-0

 

Active virus. That sounds like what I have got. Recurring viruses.

And I would bet that if those patients are like me then many of those not showing active virus would do so if measured two weeks later as my viruses activate in a cyclical seesaw with the innate immune system activating to fight the virus then deactivating only to allow the virus back.

So why is it Latvian medical research academics can focus effectively on relevant factors with a coherent cohort to achieve a telling outcome and the academia of the western world has been chasing CFS criteria like a dog chasing its tail, for twenty years?

We have got to break the habit of the ineffectual approach to criteria bequeathed by the BPS blaggers.

 

This looks important, but I don't know how important, or not.

I know HHV-6 and 7 have been looked at before. As well as cytokines.

How significant is this research?

And agreed, @boolybooly, how come Latvian researchers have done this when we're still in a muddle. Granted, there is lots of research going on, but we never seem to get much replicated or any thing really definitive, as in something new and certain to add to the knowledge we have.

 

Fukuda, unfortunately. According to figure 2 only 58% of patients reported PEM.

It's a reasonably large cohort so it would be interesting to reanalyse the data for patients with and without PEM separately, assuming the raw data have been recorded in a way to allow this. There's no mention of data availability but if any of the authors happen to be reading this...

 

So if Fukuda was used then you have to wonder why the result because Fukuda is almost every chronic inflammatory illness IMHO.

https://me-pedia.org/wiki/Fukuda_criteria

Two possibilities occur to me.

One is there is a lot more recurring virus in Latvia so when they pick a random sample of patients more of them have recurring virus like me.

Two is the clinicians who pulled the cohorts together have a clearer idea of what they are looking for, with non explicitly applied criteria or even an unconscious characterisation of the type of the condition they are trying to investigate leading to unconscious bias, i.e. cherry picking, which I would regard as beneficial in this case as it gives us something to think about.

The thing is, in either case, there is a need to define a cohort more concisely to assist replication because if you take this to another location with different clinicians typically you might see a different result.

So my suggestion would be to define a cohort by the experimental outcome i.e. presence of active virus as well as the CFS criteria. Then you would have a refined subtype and could expect more consistent results. This method would be broadly applicable to a lot of the apparent discoveries which have proved difficult to replicate.

 

Fukuda allows a wide variety of illnesses, but the actual composition of the cohort is maybe highly reflective of the place of recruitment. Maybe the authors are recruiting patients from clinics where there are much more patients with active viral infections compared to other places.

 

I just read the abstract. Often that's too much to read re cognitive fatigue. The case definition wasn't in the abstract. Now that I know Fukuda criteria was used, this study is way less exciting.