Working out of a small laboratory called IncellDX, which Pitchbook states has just 23 employees, Bruce Patterson MD has managed to have an outsize effect on the long-COVID field. More patients (many more) are reportedly using his protocol via an array of doctors he works with – more than have been enrolled in the NIH’s $.1.5 billion RECOVER thus far.
Patterson’s managed to do this by making himself available again and again to the press and social media over the past two years. I counted over 2 dozen YouTube presentations featuring Patterson over the past two years. Recently, Patterson appeared on the Solve ME/CFS Initiative/BIO webinar and in a follow-up talk with Dr. Drew. He also recently published a case series of treatment reports.
Two plus years since Patterson reported he thought that he’d uncovered the cause of long COVID, it’s a good time to catch up using a couple of presentations Patterson has recently made with Dr. Drew and in the recent Solve M.E./BIO webinar.
Patterson probably wasn’t expecting Dr. Drew to start off his recent interview 3 months ago the way he did. Seemingly without having a clue about the fix he was putting his guest in, Drew blithely noted that the drug Leronimab, which had shown so much promise early in the pandemic, just didn’t work out. “What about that?”, he asked Patterson.
Leronimab, it turns out, was Patterson’s first choice several years ago. In fact, Patterson got slapped down by the FDA after stating in a TED talk that the drug was saving the lives of severely ill COVID-19 patients. Patterson also attempted, but failed, to take over the company that produces Leronimab.
Patterson, after understandably stumbling a bit, asserted that the CCR5 pathway – which Leronimab blocks – plays a key role in long COVID, chronic fatigue syndrome (ME/CFS), fibromyalgia, and post-treatment Lyme disease. He also suggested there may have been some issues with the “offering”.
With Patterson’s audio cutting out frequently, it was a bit of a rocky start. Dr. Ram Yogendra – a board-certified anesthesiologist researcher on several of Patterson’s papers – cut in.
Yogendra provided a moderating counterpoint to Patterson’s sometimes more exuberant statements. Yogendra emphasized that their understanding of long COVID and diseases like ME/CFS, FM, and post-treatment Lyme disease syndrome (PTLDS) is still evolving. He said they get patients who expect that the 2-drug combo Maraviroc and Pravastatin is going to be it, and are disappointed to find their case more complicated and much more testing than they expected needed. He encouraged patients not to expect one magic drug or drug combination to do the trick.
Noting that they’re still trying to define what pure long COVID is, Yogendra said they were still very confident that the S1 protein from the spike protein of the coronavirus was driving long COVID but that “not everyone has that profile”.
Indeed, their main hypothesis remains the same as it was 2 1/2 years ago. They believe (and have found) that a SARS-CoV-2 virus protein called S1 is persisting in non-classical monocytes. They believe those monocytes – whose sole job is to bind to the blood vessels via the fractalkine receptor pathway – are making their way to the blood vessels and causing damage and clotting. Patterson also believes they’re making their way through the blood-brain barrier into the brain.
These monocytes usually live only a week or so, but the protein short circuits the apoptosis (suicide) pathway – causing them to live much longer than usual. These same monocytes can carry viruses into the brain.
Calling them “a garbage can for viruses and bacteria and proteins”, Patterson clearly believes similar monocytes may be playing a major role in diseases like “long-Lyme disease” and ME/CFS. One wonders if Patterson has begun a search to determine if a Lyme or Epstein-Barr virus protein is persisting in ME/CFS patients’ monocytes.
Reactivation of the herpesviruses or the Lyme virus, and other factors means, Yogendra said, that the etiology and pathophysiology is “all over the place” – indicating once again, that a cookie-cutter solution does not work. Yogendra also reported that over the past 6-12 months, they’ve been doing more and more testing – another sign that the 2-drug combo is not the be-all and end-all. In that vein, he reported kids – who haven’t been exposed to as many pathogens as adults – tend to respond more quickly; i.e. they’re not as complicated.
Yogendra stated that 20 to 30% of patients with ME/CFS and PTLDS are not having the response they wanted to see and they are exploring them further. (Patterson is apparently using the same immune factor set that popped up in long COVID to assess his ME/CFS and other patients, and one wonders if that is sufficient.) Patterson stated that viral reactivation – which honestly no one to this point has really seemed to treat well – is a really important part of ME/CFS and Lyme.
It was good to hear Yogendra moderate expectations. If Patterson has, at times, hedged his bets in the past (has he?), those hedges were largely lost in the excitement over his claims that he’s identified the cause of long COVID. As time has gone on, though, long COVID has clearly gotten more complicated – not less – with studies finding over 200 symptoms and suggesting that multiple kinds of long COVID exist.
Patterson believes there is one common factor, though, that’s present in all these diseases (long COVID, ME/CFS, FM, Post-treatment Lyme) – and that’s vascular inflammation. (Certainly, studies have found evidence of blood vessel or endothelial cell problems in all these diseases. Note, though, that thus far, clotting problems seem to be more prevalent in long COVID than ME/CFS).
Patterson said that CD40L – the first protein producing in the clotting pathway is increased in his long-COVID patients – indicating that an inflamed endothelium (blood vessels) is present. VEGF – which promotes blood vessel growth – is also commonly increased, and is associated with neuropathic pain and other symptoms.
An ME/CFS and Long-COVID Connection
If Patterson’s findings describe both long COVID and ME/CFS, they should have popped up in the ME/CFS research literature, and at times they have. CD40L and VEGF both popped up in a Stanford ME/CFS study that assessed levels of 51 immune factors before and 18 hours after exercise. The study found, though, reduced – not increased – levels of CD40L post-exercise.
Interestingly, three of the five most discriminatory cytokines post-exercise in ME/CFS (CD40L, platelet activator inhibitor, CXCL1) affect the blood vessels – the big battleground in Patterson’s scenario. Plus, two blood vessel factors – CXCL10, vascular endothelial growth factor (VEGF) (as well as IL-15) were reportedly “highly connected with other cytokines in the ME/CFS network.”
Both White (2010) and Hornig (2015) also found reduced levels of CD40L – in Hornig’s case, in the short-duration illness group. (She found comparatively higher levels in the longer duration group.) Hornig also found reduced levels of platelet-derived growth factor in short-duration ME/CFS patients when compared to controls.
On the other hand, CD40L was increased in patients with PI-CFS (post-infection CFS) and other persons with fatigue after Giardia infection, and correlated well with fatigue levels. Another study found a significant increase in CD40 receptors on mast cells in severe CFS/ME patients.
The CD40L findings, like so many immune findings, are all over the place in ME/CFS, but the main takeaway may be that one way or another, they keep popping up. Something appears to be going on with these cells that play a big role in Patterson’s long-COVID hypothesis. An EBV study also found increased CCR5/RANTES activation in ME/CFS.
Patterson’s core findings should be showing up in other long-COVID studies, and some of them have. Other studies have found evidence of T-cell exhaustion and Epstein-Barr virus reactivation.
The really big surprise, though, has been monocytes and ME/CFS. Patterson’s big goal is to stop coronavirus protein-carrying monocytes from migrating to the blood vessels in long COVID.
Monocytes, on the other hand, have hardly been mentioned in ME/CFS for decades. (They were a big deal in the RNase L hypothesis, which eventually fell apart.) They were basically a no-show in ME/CFS, until recently, when they suddenly showed up big time.
The more effective gene expression methods Grimson used in an NIH-funded ME/CFS research center study revealed a big surprise: monocytes might actually be at the heart of what’s going on in ME/CFS.
Grimson found the strongest center of immune dysregulation occurred in monocytes – particularly classical monocytes. (Note that Patterson is focused on non-classical monocytes). Grimson found that the percentage of diseased classical monocytes was highly, highly correlated with fatigue (P<.00057 (!)). He also found increased levels of the chemokine CCL4, which specifically attaches to CCR5 receptors – a key player in Patterson’s hypothesis. Grimson wrote that the highly activated and aggressive monocytes he found:
“could contribute to many of the symptoms of ME/CFS. This work sets up lots of questions that motivate our work now – where are the monocytes going in ME/CFS individuals, what is causing them to be dysregulated, and ultimately, can we reverse this dysregulation?”
Grimson’s further statement – “ME/CFS patients experience continual improper recruitment of monocytes to one or more tissues” – seems quite in line with what Patterson seems to be suggesting – similar, albeit with nonclassical monocytes – they are moving into and harming the blood vessels.
Nonclassical monocytes are generally thought to be anti-inflammatory and are confined to the blood vessels but can be associated with the disease. Classical monocytes, on the other hand, are considered pro-inflammatory and could be attacking many tissues.
Other monocyte findings have popped up in COVID-19 and long COVID. Avindra Nath found extremely aggressive monocytes that were associated with the blood vessels in COVID-19. A Swedish study found activated and unusually long-lived classical monocytes in long-COVID patients six months after infection. A German study found a “profound dysregulation” in almost all soluble factors associated with monocyte/macrophage biology and a study linked CD9+ monocytes to the development of long COVID.
While monocytes (and many other immune cells) have shown up in long COVID no one yet has tried to validate Patterson’s core finding – that nonclassical 16+ monocytes a) are carrying the S1 spike protein in long COVID and b) that they’re migrating to the blood vessels and causing harm. Two years later, the CD16+ monocytes Patterson is so focused on have received little study in long COVID.
Patterson’s first goal is to treat the chronic inflammation. Maraviroc’s ability able to affect inflammatory cells across the body, but not suppress the immune system, makes it an ideal drug for him. A CCR5 antagonist, Maraviroc, was the first in a new class of retroviral drugs developed to treat HIV. It apparently blocks the receptor that allows immune cells to respond to the chemokines that direct immune cells to the tissues.
Statins – developed to prevent atherosclerosis – then prevent cells from binding to blood vessels. That turns off the anti-apoptotic (anti-suicide) process causing the uber-long-lived monocytes to finally die. That’s why the effect is purportedly permanent. Patterson stated that their testing shows the numbers of these cells dropping over time.
Precision Medicine Approach
At least three precision medicine approaches are being done in these diseases. Patterson’s, Hyman’s CIRS group, and an Australian group are using gene expression, or other results, to track their patients and modify their treatment regimens.
If Patterson sees high levels of cytokines, for instance, he may try to block them using a treatment. Patterson reported that his results indicate that increased levels of IL-2 and TNF-a, for instance, are strongly correlated with fatigue. CD40L and VEGF, on the other hand, are correlated with neural symptoms and dysautonomia. Their latest paper – which is not out yet – correlated cytokines/inflammatory markers with symptoms.
Validating that paper’s findings could open the door to targeting symptoms using cytokine blockers and other agents. It was recently argued in the Solve M.E./BIO webinar that associating symptoms with biological factors is a much better and more efficient way to approach chronic diseases. Instead of diagnosing a patient with x disease and trying to hit that very variable target with a drug, you simply show, probably through gene expression results, that x-factors are associated with say, fatigue, and then you target that factor.
The differences Patterson reports are intriguing given the really close fit we’ve seen between the results of ME/CFS and long-COVID studies. With his precision medicine approach, and his ability to compare disease cohort to disease cohort, Patterson is taking a more fine-tuned look at these diseases than most. The Bateman Horne Center/Jax Laboratory and Lenny Jason (and surely others) are also comparing ME/CFS and long-COVID cohorts. It’ll be fascinating to see how closely or not closely connected they end up being as they’re put more and more under the microscope.
The Case Series Report
Patterson, Yogendra et al. recently published an 18-person case series report: “Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC)“.
Sometimes patient results are presented in chronological order; that is. every patient seen between x and y date is reported on. This case series, though, plucked out patients who had seen improvement on the protocol.
The study found that the treatment did change the levels of the cytokines Patterson believes are driving these diseases and that the levels of the cytokines were positively associated with some symptom scores; i.e. using the two-drug combo to drop the levels of the cytokines improved symptoms.
The results were not overwhelming, however. Changes in the Rankin disability scale, for instance, demonstrated a “low positive” correlation with changes in VEGF and sCD40L levels. Similarly, changes in autonomic nervous system scores (COMPASS) had low positive correlations with TNF-alpha and GM CSF levels and moderate positive correlations with VEGF and sCD40L. Changes in functional test scores had a low positive correlation with IL-8, and GM-CSF. Finally, changes in fatigue scores showed moderate positive correlations with IL-2, sCD40L, TNF alpha, and VEGF, and low positive correlations with IL-8, IL-10, and GM CSF.
With regard to the immune factors that Patterson believes are driving long COVID, all the authors could say was:
“Our results suggest that there are a number of biomarkers that appear to be positively associated in varying degrees with the various subjective scores.”
A similarly underwhelming result showed up when they assessed whether the treatments were sufficient to move a patient from one disease severity state (0 = Normal, 1 = Mild-Moderate, 2 = Severe, and 3 = PASC) to another; i.e. from mild/moderate to normal or severe to mild/moderate, etc. Although the statistical analysis showed that patients were better off after the treatment than before (see below), a machine learning model did not, if I’m reading this right, find their disease classifications, in general, had changed.
Simply assessing symptom scores (fatigue, autonomic, functional, etc.) before and after treatment, however, suggested that significant improvements – particularly in fatigue and autonomic nervous system symptoms – had occurred.
As this was a self-picked case series, it doesn’t tell us anything about the efficacy of Patterson’s protocol in general. That will have to wait for a placebo-controlled, randomized trial that Patterson stated is going to start later this year.
- With 30,000 long COVID, ME/CFS, FM, and Lyme patients taking his tests and trying his protocol, and with tests available in the U.S., the UK, Europe, and Brazil, Bruce Patterson has become a juggernaut in the long COVID treatment realm.
- Patterson asserted he’s found the cause of long COVID (and possibly ME/CFS/FM and Lyme) in dozens of Youtube presentations and interviews over the past two years.
- During a recent presentation featuring him and a fellow researcher, Dr. Yogendra, Yogendra presented something of a moderating viewpoint. While they believe their thesis – that unusually longlived immune cells called monocytes are honing in on the blood vessels in long COVID – still stands Yogendra said their understanding of long COVID is still evolving. Long COVID is turning out to be quite complicated and different kinds of it exist.
- That means that the two drug Maraviroc and Prevestatin combo is not always the be-all and end-all treatment. At times further testing and other treatments may come into play.
- ME/CFS, not surprisingly, is more complicated with 20-30% of patients not progressing like they hoped they would.
- One common factor, though, they believe that’s present in all these diseases (long COVID, ME/CFS, FM, Post-treatment Lyme) is vascular or blood vessel inflammation.
- Study results in ME/CFS present some similarities and dissimilarities. A key factor in Patterson’s model of long COVID has shown up in ME/CFS research but in reduced not increased levels.
- Interestingly, though, Patterson’s major focus in the immune system – monocytes – recently showed up big time in a major ME/CFS research study. That study suggested that monocytes (albeit a different kind of monocyte) are ground zero for the immune dysfunction found in ME/CFS. That was remarkable given monocytes have received almost in ME/CFS until now.
- Some of Patterson’s early findings – T-cell exhaustion, herpesvirus reactivation, Lyme reactivation and vaccine-induced long COVID – have been showing up elsewhere.
- Patterson’s recent report on a case series of long COVID patients who had improved on his treatment protocol had mixed results.
- Reductions in the key cytokines that he believes are driving long COVID (and ME/CFS/FM) symptoms were, at best, only moderately associated with improvements in symptoms. More importantly, though, the study did appear to find significant reductions in fatigue, dysautonomia, and other symptoms.
- Patterson has been taken to task at times for moving too quickly to promote his approach. During a recent talk, Patterson noted that being in the corporate world has allowed him to disseminate his findings and ideas to the long COVID patient population much more quickly allowing him to diagnose and treat many more long COVID and other patients than he would have otherwise.
- That’s undoubtedly true. Dr. Shungu’s fourteen-year NIH-funded assessment of the effectiveness of just one substance (NAC) in ME/CFS amply demonstrates how terribly long and drawn out and ultimately not feasible for patients the academic approach can be.
- Still, without a clinical trial – which Patterson says is coming this year – thousands of long COVID, ME/CFS/FM, and Lyme patients have been spending thousands of dollars in hopes that Patterson is correct. In light of that, despite the obvious shortcomings of any online poll one that attempts to give some idea of his protocol’s efficacy is provided.
It’s still hard to know what to make of Patterson. He came up with a novel hypothesis and approach to long COVID very early on. He was one of the first to acknowledge that herpesvirus reactivation sometimes occurs, was the first that I know to talk about Lyme reactivation – including in patients who didn’t know they’d ever been exposed to Lyme, and one of the first to find the vaccine-induced “long COVID” that sometimes occurs.
Whether Patterson is right or not, he’s another example of the creativity that’s been unleashed by long COVID and the novel approaches to it, and diseases like ME/CFS that have shown up. No one was talking about monocytes, antiretroviral drugs or statins in ME/CFS before Patterson showed up.
An academic with a long record of achievement, he’s now out on the skinny branches, though, asking sick people to trust him that his diagnostic and treatment protocol works. That’s engendered some criticism, but the patients have been responding to his message of hope.
His company, IncellDx is booming. It just launched in Australia and is already live in the European Union (EU), the United Kingdom (UK), and Brazil. It’s started a collaboration with Igenex in the US – which Patterson called a global leader in Lyme testing – to help them ferret out post-treatment Lyme patients.
This is in part because Patterson has made trying out his protocol very easy. At COVIDlonghaulers.com you can order $910 worth of tests (in the US), schedule a blood draw, get your results from the lab and talk to one of Patterson’s collaborating doctors. The doctor’s notes and recommendations will then be sent to your primary care provider, who will be responsible for prescribing the medications. It’s a wonderful system.
In a recent talk, Patterson, a former academic, pointed out an interesting advantage of being in the corporate world – the ability to scale up quickly and disseminate his findings. It’s that ability, he said, that is allowing him to reach more patients.
He certainly has a point. Take Dikoma Shungu’s NAC study in ME/CFS. It took 9 years for Shungu to definitively show that low brain glutathione levels are present in ME/CFS. In 2012, Shungu received an R21 (small exploratory) grant to investigate whether NAC – a glutathione enhancer – might be helpful.
Eight years later, in 2021, Shungu got his BIG grant – an RO1 grant – to thoroughly investigate the effects of NAC in ME/CFS. That study is projected to last through 2025, with the results hopefully ready sometime in 2026. It will have taken 14 years – a fifth or so of a normal person’s lifespan – to study the effects one substance in ME/CFS using the standard academic approach.
So yes, Patterson is bashing through some norms, but at least it won’t take 15 years to know if he’s right or not.
(Health Rising is not associated with Bruce Patterson or IncellDx in any way).
The Patterson Poll
It’s not really fair to assess treatment efficacy using an online poll. We don’t know who is taking the poll. It’s possible the poll could undercount people who had positive results and went on with their lives. We don’t know how well the participants adhered to the treatment protocol, or how well the doctors treating the patients did, or what additions they made to it, what other health issues the patients brought to the table, etc.
Dr. Patterson, though, has promoted his diagnostic and treatment plan again and again over social media and the internet, and in the absence of a clinical trial, the only thing we can do is do a poll. So, take the results as you will – here’s the poll.