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And now for another controversial post… 🙂 A preprint of the Yale Akiko Iwasaki/Harlan Krumholz post-vaccination syndrome study, “Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination“, was recently published.

Coronavirus vaccines

Over 100 million people have engaged in vaccine trials worldwide…
(Image by torstensimon from Pixabay )

Vaccine blogs draw a lot of heat, but please note that comments touting conspiracy theories will not be allowed. Nor will comments asserting that vaccines are responsible for everything under the sun. We’re not going down those rabbit holes again.

Vaccine Studies

Let’s get some study evidence out of the way.

The fact that coronavirus vaccinations reduce the risk of long COVID is not in doubt. A meta-analysis of 25 studies involving 14 million people concluded that 1 and 2 vaccinations were associated with a 15% and 24% reduction in the risk of coming down with long COVID after a coronavirus infection.

Nor is the fact that the coronavirus vaccines saved many lives in doubt. Across the world, over 100 million people have participated in coronavirus vaccine trials. By Nov 2022, the U.S. has administered more than 655 million doses to US residents, which, a modeling study estimated, saved more than 18 million additional hospitalizations, more than 3 million additional deaths, and $1.15 trillion in additional medical costs.

Nor should anyone question whether the vaccines also caused problems, at times. The authors noted that rare adverse events, such as myocarditis and pericarditis, thrombosis and thrombocytopenia, Guillain–Barre syndrome, transverse myelitis, and Bell’s Palsy were associated with vaccination.

How rarely did these conditions crop up? Very, very rarely (myocarditis (usually minor) 4.8 cases per 1 million doses; Bell’s Palsy – 25.3 per 1,000,000 doses; thrombosis – 0.21 cases per 1 million; Guillian-Barre – 32.4 per 100,000 person-years (Jansennen vaccine); transverse myelitis – 1.82 cases per million vaccine doses). The fact that vaccine studies picked these rare conditions up at all is a testament to how effective they were at picking up diseases the medical system is tracking. In every case, having a coronavirus infection places a person at risk of contracting these diseases more than a coronavirus vaccination does.

On the other hand, it’s clear that the studies have been very poor at picking up people with what is now called “post-vaccination syndrome” (PVS). PVS appears, symptom-wise, to be a dead ringer for ME/CFS and long COVID (exercise intolerance, excessive fatigue, numbness, brain fog, neuropathy, insomnia, palpitations, myalgia, tinnitus or humming in ears, headache, burning sensations, and dizziness). The fact that PVS hasn’t shown up in post-vaccine studies only demonstrates that you can’t find what you’re not looking for.

A big question that will be difficult to answer – given how many people were also infected with the virus – is how many people have post-vaccination syndrome.

Immune System Tweak

The authors suggested several ways that tweaking the immune system to protect against the virus can, in some people, cause symptoms identical to the virus.

The different components found in vaccines, “mRNA, lipid nanoparticles, and adenoviral vectors”, could be activating the pattern recognition receptors, which trigger the early, or innate, immune response. The spike protein could trigger symptoms. Referencing Dr. Patterson’s work, the authors noted that non-classical monocytes of some people with PVS had been shown to contain the S protein. Plus, in animals the protein has been shown to cross the blood-brain barrier. Finally, the immune responses triggered by the vaccine could produce an autoimmune reaction.

The Study

The small study took a deep dive into the “immunophenotypic profiles” (circulating immune cell populations, antibody responses, circulating immune modulator levels, spike protein) in 42 people with PVS and 22 healthy controls who had been vaccinated.

One possible confounder was that tests revealed that 27/42 people with post-vaccination syndrome had also been exposed to the coronavirus at some point. Most PVS patients, however, reported reacting to the vaccine within 10 days, so it’s assumed that their reaction was to the vaccine. Some of the immune findings could, however, result from a coronavirus infection.

Results

Not surprisingly the study found that the health status of the PVS patients was “far below” the normal and they reported a lower quality of life. The most common symptoms were excessive fatigue (85%), tingling and numbness (80%), exercise intolerance (80%), brain fog (77.5%), difficulty concentrating or focusing (72.5%), trouble falling or staying asleep (70%), neuropathy (70%), muscle aches (70%), anxiety (65%), tinnitus (60%) and burning sensations (57.5%).

B-cells activation

Once again, B-cells were not getting activated. Could ME/CFS, long COVID, and PVS start here?

Unswitched Memory B-Cells

The finding that the proportions of unswitched memory B cells (US memory B cells; CD19+/CD27+/IgD+) were significantly higher (p= 0.02) in the PVS patients was intriguing given similar findings in ME/CFS.

Nath’s intramural study found higher levels of naïve (immature) B-cells and decreased numbers of mature memory B-cells. Nath proposed that the high levels of immature B-cells might constitute “the primary defect” in ME/CFS, potentially leading to immune exhaustion and activation of innate immune responses.

Thus far, the T and B-cell findings in ME/CFS  point to problems with energy production. Could ME/CFS be ahead of the game regarding T and B-cell failings?

The Vampire: Is the Immune System Sucking the Energy Out of People with ME/CFS? – the NIH ME/CFS Conference Pt. I

T-Cell Exhaustion

The “reduced CD4+ T cell subsets in circulation and an increased percentage of TNFα+ CD8 T cells”, plus higher levels of exhausted CD8 (cytotoxic) T-cells, again seems reminiscent of findings in ME/CFS and long COVID. The increased percentages of the cytotoxic T-cell subset suggests that the T-cell exhaustion is driven by chronic activation by a virus or pieces of a virus.

Increased Classical Monocytes

Reduced cDC2 cells and increased levels of non-classical monocytes suggest an impaired immune response to the virus, chronic inflammation, particularly in the blood vessels, and an increased risk of autoimmunity. The activation of classical monocytes plays a key role in Bruce Patterson’s hypothesis of long COVID-19.

A Bruce Patterson Interlude

Bruce Patterson MD raised a lot of interest – and controversy – when he went on a social media tour in 2020/2021 claiming that he knew what caused long COVID, had developed tests to diagnose it, and a protocol to treat it. Time will tell how right Patterson was about all that, but it should be noted that his hypothesis – that an overactive innate immune system that is attempting to compensate for T and B-cell deficiencies – is very similar to what Nath and others have proposed.

Bruce Patterson MD

Bruce Patterson MD (with Health Bio) has begun a large long COVID clinical trial.

Patterson found atypically long-lived classical monocytes carrying the spike protein in long COVID, and very early on proclaimed that post-vaccination syndrome was happening. Patterson also highlighted herpesvirus reactivation and asserted that other pathogens (Lyme disease) were also becoming reactivated. Patterson’s Aug 2024 paper used machine learning and cytokine findings to differentiate chronic Lyme disease from long COVID.

Has Bruce Patterson Cracked Long COVID?

Two weeks ago, Patterson and his company, HealthBio (formerly IncellDx) put their money where their mouth was when they announced they’d begun a massive phase III, 32-week randomized, 252-patient, double-blind, placebo-controlled, multicenter trial assessing the effectiveness of Patterson’s protocol (Selzentry (maraviroc) and Lipitor (atorvastatin)) in long COVID.

Patterson may not be all over social media anymore—drawing attention and criticism for his provocative findings—but HealthBio is certainly not holding back about how earth-shattering it believes its findings are. The HealthBio website states that “HealthBio has discovered the root cause and solution for diagnosing and treating chronic inflammatory diseases,” including ME/CFS, post-treatment Lyme disease, and fibromyalgia.

EBV Reactivation Found

The GIST

  • A preprint of the Yale Akiko Iwasaki/Harlan Krumholz post-vaccination syndrome study, “Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination“, was recently published.
  • Vaccine blogs draw a lot of heat, but please note that comments touting conspiracy theories will not be allowed. Nor will comments asserting that vaccines are responsible for everything under the sun.
  • Over 100 million people have participated in vaccine studies worldwide and the results are pretty clear. Coronavirus vaccines have saved many lives, prevented many hospitalizations, and are protective against long COVID. In very rare cases, they increase the risk of developing some diseases, but coronavirus infections increase the risk of contracting these diseases more.
  • The vaccine studies, however, have been very poor at picking up signs of what is now called “post-vaccination syndrome” or PVS whose symptoms are a close match to those found in long COVID, ME/CFS and fibromyalgia. We simply don’t know how many people have PVS.
  • This 42-person study delved deep into the immune systems of people with PVS. Several findings—a lack of B-cell maturation, T-cell exhaustion, increased classical monocyte levels, Epstein-Barr virus (EBV) reactivation, and a persistent spike protein—appeared to mimick findings in long COVID and/or ME/CFS.
  • A  familiar theme of innate immune system activation attempting to compensate for the failure of the T and B cells to fight off the virus seemed to emerge.
  • While not all PVS patients had the spike protein, in some cases, it was still present over two years after infection – suggesting the protein may still be tweaking their immune systems.  Much work is underway better to understand viral persistence’s role in long COVID.
  • Greater reactivity to Epstein-Barr virus (EBV) proteins associated with cytotoxic T-cell activation suggested that EBV reactivation was tweaking the PVS patients’ immune systems as well. Therefore, either of the viruses could be causing or contributing to the symptoms found in long COVID-19.
  • The classical monocyte finding seemed to echo Bruce Patterson’s findings of two years ago. Patterson and his company Health Bio recently began a large phase III clinical trial of their approach to long COVID.
  • A machine learning approach, which found that hormones and neuropeptides associated with stress response, pain-detecting nerves, and immune activation were associated with PVS, brought more similarities to ME/CFS, FM, and long COVID.
  • The Yale team received heat from traditionalists and vaccine conspiracists. Traditionalists didn’t want to hear about PVS right now, given RFK Jr.’s ascension to a leadership position, and vaccine conspiracy theorists got a boost from Elon Musk, who, despite the fact that long COVID predated the coronavirus vaccines, tweeted that “they are finally admitting “Long COVID” is just vaccine injury.”
  • While small, this study was good news for anyone with post-coronavirus vaccination syndrome or any kind of post-viral vaccination syndrome (PVS).
  • Getting results similar to those found in long COVID and/or ME/CFS suggested that finding an answer to those diseases will also help people with PVS

“A powerful and versatile technology for analyzing antibody responses” serum epitope repertoire analysis (SERA) assessed which viruses the participants had been exposed to. The analysis indicated that the post-vaccination syndrome (PVS) patients were not sick because they had been exposed to more pathogens.

Next, the researchers want to see if the PVS patients’ immune systems were more activated against proteins found on EBV’s outer envelope. EBV uses both these proteins (EBV gp42, EBV gp350) to bore into and infect B-cells. Increased antibody levels against both of these proteins suggested the PVS patients were fighting off EBV reactivation. (Vaccines to block EBV gp350 are being studied.)

A positive correlation between PVS patients with greater antibody reactivity to gp42 and increased TNFα-producing CD8+ T-cells suggested that EBV reactivation was indeed turning on the T-cells (which were becoming exhausted).

Spike Protein Shows Up

coronavirus

A lot of attention is being focused on the spike protein (red appendages)…

The coronavirus vaccines introduce the spike protein – the part of the coronavirus that infects cells – in different ways. mRNA vaccines (Pfizer-BioNTech and Moderna) deliver instructions to the immune system to produce it. The Johnson and Johnson vaccine modifies the virus so that it tells cells to produce the protein and Novovax directly introduces the spike protein.

There are many reasons vaccine makers have focused on this particular protein: it allows the coronavirus to infect the cells, it’s easy to target, antibodies to it can neutralize the virus, etc.

The authors stated that perhaps the most notable finding was elevated levels of spike (S1 and full-length S) up to 709 days after vaccination among a subset with PVS, even in those with no evidence of detectable SARS-CoV-2 infection. This was a bit surprising because, by 14 days, the spike protein is usually undetectable, but it does fit with Bruce Patterson’s findings of the spike protein in non-classical monocytes long after vaccination (or infection).

Of course, the idea that the long-term persistence of the spike protein might trigger symptoms via inflammation and blood clotting in long-term COVID-19 is not new.

As we’ve seen in long COVID – not everyone with PVS had high S1 levels. Still, as a group, the PVS group had higher S1 levels than a long-COVID group the researchers tested.

Predicting Post-Vaccination Syndrome

A machine learning approach suggested that the hormones (hypothalamus, pituitary glands) and neuropeptides associated with stress response and pain-detecting nerves (oxytocin, neurotensin, ꞵ endorphin, melanocyte-stimulating hormones (MSH), substance P) were negatively associated with PVS.

Signs of EBV reactivation and immune activation (anti-EBV gp42 IgG titers, MMP1 levels, and TNFɑ+ CD8 T cells) were positively associated with the PVS.

Controversy

Doing a post-vaccination syndrome study was bound to upset both traditionalists and conspiracy theorists…

Knowing that the findings would be controversial (and misinterpreted), the authors emphasized the small study size and the need for replication and validation. Iwasaki even noted that it was too early to differentiate meaningful results from random fluctuations in the data. Some lambasted Iwasaki and Krumholz for even doing the study, given the anti-vaccine movement and, now, RFK Jr.’s ascension to a leadership position.

Dr. Iwasaki called it “the first kind of glimpse” at what was going on in post-vaccination syndrome, and pledged more studies to come.

The misinterpretations and over-reactions came quickly. Elon Musk did his credibility no good when, ignoring the fact that long COVID appeared long before the vaccines were available, he told his 218 million followers on X.com that “they are finally admitting “Long COVID” is just vaccine injury“. STAT News reported that Iwasaki said, “Oh, no! Really?”, when told of that.

This isn’t the first time that Musk has been way off with COVID-19. Musk referred to the coronavirus as a “specific form of the common cold”, stated that “the coronavirus panic is dumb”, and predicted that there would be “close to zero new cases” in the US by the end of April 2020. He also bet podcaster Sam Harris $1 million that the US would not exceed 35,000 COVID-19 cases. (As of Feb 2025, over 110 million coronavirus cases had been confirmed (and the total is likely much greater).)

Conclusion

While small, this study was good news for anyone with post-coronavirus vaccination syndrome or any kind of post-viral vaccination syndrome (PVS). PVS has been an issue in ME/CFS for decades, but it took over 100 million American vaccinations for a few researchers to start taking it seriously. (The next vaccine studies—when and wherever they occur—should include PVS in their assessments.) Thankfully, this study came from a highly respected Yale research team led by Akiko Iwasaki.

It was very good to see findings broadly similar to those found in long COVID and ME/CFS pop up. The increased number of unswitched B-cells and classical monocytes, the T-cell exhaustion and EBV reactivation all seemed to parallel findings in long COVID and/or ME/CFS. A familiar theme of innate immune system compensation for a failure of the T and B-cells to fight off the virus seemed to show itself.

Finding evidence of the spike protein in some cases two years post-infection in some PVS patients also fit with long-COVID findings suggesting that pieces of the virus may still be activating the immune system, and a great deal of work is investigating this possibility.

The classical monocyte finding also seemed to echo Bruce Patterson’s findings of two years ago. It also brought to mind Grisham’s unexpected finding suggesting that monocytes play a key role in ME/CFS. Patterson’s company HealthBio recently began a large multicenter trial of Patterson’s protocol in long COVID.

A machine learning approach, which found that hormones and neuropeptides associated with stress response, pain-detecting nerves, and immune activation were associated with PVS, brought more similarities to ME/CFS, FM, and long COVID.

Getting results similar to those found in long COVID and/or ME/CFS suggested that finding an answer to those diseases will also help people with PVS. While bigger studies are needed, the PVS research field got itself off to a good start with this one.

 

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