I’ll just get straight to the point: cytokine testing didn’t work for ME/CFS and it doesn’t look like it will work for Long COVID or post-vaccination syndrome. The tests are probably a waste of money right now.
What are cytokines
Cytokines are small proteins that are important in cell signaling. Your immune system uses them for signaling. Wikipedia has a longer description if you’re interested:
Cytokines are a broad and loose category of small proteins (~5–25 kDa[1]) important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.
ME/CFS hype
*CFS = chronic fatigue syndrome
In 2010, Broderick and colleagues published A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome. They measured the levels of 16 different cytokines in 40 female CFS patients and 59 controls. They were looking for any patterns that might distinguish the CFS patients from controls.
Fast forward 9 years later and it was becoming clear that cytokines weren’t panning out. In 2019, Yang and colleagues published a review paper on cytokines where they concluded:
Moreover, there is no evidence to support the use of CSF cytokines as independent diagnostic indices. Nevertheless, a comprehensive evaluation of changes in circulating and CSF cytokines may improve clinical understanding of the pathophysiology of patients with CFS, aiding in the establishment of an appropriate diagnosis. Importantly, the available evidence does not support the value of cytokines as therapeutic targets. We believe that an improved understanding of cytokine-related mechanisms will be helpful to explore new cytokine-related therapeutic targets.
The clinical value of cytokines in chronic fatigue syndrome - PMC
They’re saying that it’s not a useful diagnostic and that you shouldn’t use cytokines as a benchmark for whether or not the patient is getting better.
IncellDX, a company selling cytokine test for Long COVID and post-vax
Bruce Patterson of IncellDX thought that measuring cytokines would be useful in treating Long COVID and vaccine injury.
He also thought that CCR5 antagonists like leronlimab and maraviroc would be useful in treating Long COVID. CCR5 is a receptor that attaches to various cytokines, one of which is CCL5 or RANTES. The theory is that too many inflammatory cytokines in the body are (somehow) responsible for Long COVID / PASC.
Specifically, elevations in C-C chemokine ligand 5 (CCL5)/RANTES (Regulated on Normal T-cell Expression and Secretion), IL-2, IL-6, IFN-gamma and Vascular Endothelial Growth Factor (VEGF), along with decrease in CCL4 have been observed in patients and are hypothesized to be contributing to the pathophysiology of PASC (8).
Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC) - PMC
Blocking the CCR5 receptor would theoretically help correct over-activation of the immune system.
In practice it doesn’t seem to work. It turns out that the leronlimab randomized controlled trial for Long COVID was a bust.
- Cytodyn is the company that owns the rights to leronlimab. Cytodyn’s study of leronlimab on long COVID did not reach statistical significance (source: Cytodyn press release). Cytodyn claims that the trial was not designed to reach statistical significance and notes that the sample size was 56 patients. A larger trial would provide more evidence as to whether or not this drug (and perhaps CCR5 antagonists in general) is helpful.
To be fair, published papers from Patterson and colleagues argue that maraviroc (a different CCR5 antagonist) does work. A case series on patients found the following:
Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options.
The study had a weak design so it wasn’t very reliable. For example, the patients were surveyed about their baseline status after-the-fact rather than before they started treatment. Because of how patients were recruited, there may be bias because the non-responders may not want to join the study and spend time on the phone going through validated questionnaires.
Also, Patterson’s company has been known to lie in public. The @IncellDx Twitter account spread a lie about an advocate (Ria Heslop) (https://archive.ph/wip/dP9kp) through a “joint” statement with Synlab, leading Synlab to issue its own independent statement (https://twitter.com/SYNLAB_UK/status/1502655863038922760). The short story is that Patterson spread lies about Ria Heslop, a bereaved advocate, suggesting that she organized a blood draw event without IncellDX’s collaboration. The event would have had people get IncellDX-designed tests by having their blood shipped to Synlabs facilities. Because the IncellDX tweet was not factually accurate, Synlabs decided to issue their own non-joint statement that was factually accurate (though arguably very misleading).
Anyways… the point is that IncellDX lied. It is clear that their ‘joint statement’ tweet is contradicted by Synlabs’ tweet with their independent statement. So that’s one reason why you should view their scientific papers with skepticism.
“Precision” medicine
Patterson talks a lot about precision medicine, where test results would help guide clinicians in choosing how to treat patients. In practice, concierge doctors affiliated with IncellDX will prescribe/recommend maraviroc even if the CCL5/RANTES levels don’t call for it.
Survey data
Statins are one of the top treatments, although the response rate is very low like the other top treatments.
Nobody recovered on maraviroc, although the sample size was very low so the data doesn’t mean much. RCT data from the leronlimab clinical trial is more reliable and suggests that maraviroc doesn’t work.
The bottom line
Don’t waste your money. Unfortunately, because chronic illness is a Wild West right now, there’s very little accountability when it comes to people making bold claims. Very few people are calling out IncellDX for their lie on Twitter.
But at the end of the day… people are suffering. And it would be a huge disservice to those suffering to stay silent. So… no more silence. Let’s just start speaking the truth and looking out for one another.