US researchers find elevated spike protein levels in blood nearly two years after Covid vaccination

There is serious concern about the discovery by researchers in the US that people who were sick with post-vaccination syndrome (PVS) had elevated levels of virus spike protein in their blood up to 709 days after Covid vaccination.

The research by a team of 28 scientists, mostly from the Yale School of Medicine, provoked swift reactions among scientists and commentators, many of whom had already raised doubts about claims that the vaccine spike protein did not linger in the body.

In an August 2023 PolitiFact fact check the US Food and Drug Administration is quoted as claiming there is no scientific data showing that the Covid vaccine spike protein lingers with any toxicity in the body post-vaccination.

However, in a preprint published on medRxiv on February 18 entitled “Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination”, Bornali Bhattacharjee et al. report that they found elevated levels of spike (S1 and full-length S) in circulation up to 709 days after vaccination among a subset with PVS, “even in those with no evidence of detectable SARS-CoV-2 infection”.

The researchers note that some people have reported post-vaccination symptoms resembling Long Covid shortly after vaccination.

“This condition, sometimes referred to as post-vaccination syndrome (PVS) or post-acute COVID-19 vaccination syndrome (PACVS), is characterized by symptoms such as exercise intolerance, excessive fatigue, numbness, brain fog, neuropathy, insomnia, palpitations, myalgia, tinnitus or humming in ears, headache, burning sensations, and dizziness,” they wrote.

One of the preprint’s authors, Akiko Iwasaki from the Department of Immunobiology at the Yale University School of Medicine, wrote in an article for TrialSite News that their study provides “compelling evidence of immune dysregulation in individuals with chronic illness post-COVID-19 vaccination, including altered T cell populations, EBV [Epstein-Barr virus] reactivation, autoantibody production, and persistent spike antigenemia [the condition of having an antigen present in the blood]”.

While the findings warranted further investigation, they raised important questions about the mechanisms underlying prolonged post-vaccination symptoms, Iwasaki wrote.

“Future research should focus on validating these biomarkers, exploring therapeutic interventions, and refining vaccine strategies to minimize adverse immune responses,” she added.

Iwasaki told Yale science writer Mallory Locklear that it was surprising, to find spike protein in circulation at such a late time point. “We don’t know if the level of spike protein is causing the chronic symptoms, because there were other participants with PVS who didn’t have any measurable spike protein, but it could be one mechanism underlying this syndrome,” Iwasaki said.

Professor of medicine (cardiology) at the Yale School of Medicine and co-senior author of the study Harlan Krumholz told Locklear: “It’s clear that some individuals are experiencing significant challenges after vaccination. Our responsibility as scientists and clinicians is to listen to their experiences, rigorously investigate the underlying causes, and seek ways to help.”

Bhattacharjee et al. noted that, unlike Long Covid, PVS was not officially recognised by health authorities. This had significantly limited patient care and support, they said.

The researchers added: “Compared with controls, PVS participants exhibited differences in immune profiles, including reduced circulating memory and effector CD4 T cells (type 1 and type 2) and an increase in TNFα+ CD8 T cells.”

They said that the PVS cohort had significantly higher proportions of exhausted CD8 T cells.

CD8 T cells, also known as killer cells, are white blood cells that help the body fight infections and cancer. When they encounter an antigen, they activate and differentiate into cytotoxic T lymphocytes, which destroy infected, damaged, or cancerous cells. Unlike cytotoxic T cells, CD4 cells, also known as CD4+ T cells or helper T cells, don't kill cells directly. Instead, they send signals that tell other cells in a person’s immune system how to coordinate an attack against invaders.

“Serological evidence of recent Epstein-Barr virus (EBV) reactivation was observed more frequently in PVS participants,” the researchers added.

“Further, individuals with PVS exhibited elevated levels of circulating spike protein compared to healthy controls.

“These findings reveal potential immune differences in individuals with PVS that merit further investigation to better understand this condition and inform future research into diagnostic and therapeutic approaches.”

Iwasaki says that evidence of EBV reactivation in PVS patients is a troubling finding “given EBV’s well-documented role in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus”.

She said in her article for TrialSite News that elevated autoantibody levels further suggested that dysregulated immunity post-vaccination might trigger or exacerbate autoimmune responses, “raising significant concerns about long-term health implications”.

Additionally, Iwasaki said, increased TNFα+ CD8 T cell activation pointed to an ongoing inflammatory state that might underlie the systemic fatigue, neurological symptoms, and immune dysfunction reported by PVS patients.

Bhattacharjee et al. noted that there was “considerable overlap” in self-reported symptoms between Long Covid and PVS, as well as shared exposure to SARS-CoV-2 spike (S) protein in the context of inflammatory responses during infection or vaccination.

“In susceptible individuals, vaccines may contribute to long-term symptoms by multiple mechanisms,” they wrote.

“For example, vaccine components, such as mRNA, lipid nanoparticles, and adenoviral vectors, trigger activation of pattern recognition receptors. Thus, unregulated stimulation of innate immunity could lead to chronic inflammation.

“Secondly, it has been shown that the S protein expressed following BNT162b2 [Pfizer] or mRNA-1273 [Moderna] vaccination circulates in the plasma as early as one day after vaccination.

“Interaction with full-length S, its subunits (S1, S2), and/or peptide fragments with host molecules may result in prolonged symptoms in certain individuals.”

The researchers reported that a high proportion of participants with PVS developed any symptoms (70%) or severe symptoms (52.2%) within ten days of vaccination.

They said circulating full-length S had been detected in cases of post-vaccination myocarditis.

“Given the striking similarities between long COVID and PVS symptoms, there has been speculation regarding the potential causal role of the persistent presence of spike protein driving the chronic symptoms,” the researchers wrote.

Bhattacharjee et al. also noted that a recent study had shown spike protein binding to fibrin resulting in inflammation ex vivo and neuropathy in animal experiments.

“S1 subunit is sufficient to cause formation of trypsin-resistant fibrin clots when added to plasma from healthy individuals,” they said.

The researchers collected blood samples from 42 people with PVS who had no pre-existing comorbidities and from 22 healthy people who did not report PVS after Covid-19 vaccination. The blood samples were from people enrolled in the Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) study. They were collected between December 2022 and November 2023.

They assessed immune cell populations, cytokine responses, antibody levels, viral reactivation markers, autoantibodies, and circulating SARS-CoV-2 spike protein.

In addition, they evaluated the possibility that PVS might result from an undiagnosed, asymptomatic SARS-CoV-2 infection coinciding with the vaccination period instead of being directly caused by the vaccine administration.

“Our objectives were twofold: (1) to conduct a two-group case-control analysis of the immunophenotypic profiles of individuals with PVS in comparison with asymptomatic vaccine recipients, and (2) to compare the immunophenotypic profiles of those with PVS with or without a history of SARS-CoV-2 infection,” they wrote.

The researchers said they observed that the general health status of the PVS participants was far below the general US population average based on the GHVAS (patient general health assessment) scores.

“The patient-reported outcome scores from the PROMIS29 domains were also indicative of lower quality of life,” they wrote.

PROMIS (the Patient-Reported Outcomes Measurement Information System) is a set of person-centred measures that monitors and evaluates the physical, mental, and social health of adults and children. PROMIS-29 is a 29-item survey that measures seven domains of health-related quality of life.

The researchers said that the small sample size in their study limited the ability to generalise their findings to broader populations and further studies with larger cohorts were needed to validate those findings.

They added that participants self-reported symptoms, which might introduce recall bias. Also, the study selectively recruited individuals with severe PVS symptoms, possibly excluding milder cases.

While the study identified immune alterations in PVS, it didn’t establish whether these were directly caused by vaccination or other environmental factors and it was not designed to do so, the researchers said.

Independent vaccine research consultant Geert Vanden Bossche tweeted on February 20 that the WHO’s global health policy, “avidly embraced by Big Pharma”, had led to “the most insane and unprecedented interference with the immune system of individuals and even the collective immune protection of entire populations”.

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