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Study: Prolonged and Repeated Spike Protein Exposure Causing Harm

A pre-print study by M.N. Mead, J. Rose, P.A. McCullough et al titled “Compound Adverse Effects of COVID-19 mRNA Vaccination and Coronavirus Infection: A Convergence of Extensive Spike Protein Harms to the Human Body” posted on 14 August 2025 proposes the “Hybrid Harms Hypothesis” as an explanation for the severe morbidity and excess mortality in subsequent waves after vaccination rollout.


The paper is 65 pages long with the main text at about 40 pages. The remaining are the appendix and references. Excluding the Abstract and end matter, it is organized into 9 sections, including the Introduction and Conclusion.


The paper is a review and therefore does not contain data from new trials or experiments. It collates and interprets existing research—the paper has 381 references—to support its hypothesis. In this sense, there is nothing new but it does include material published in 2025, so it is a convenient and well-written paper that provides an up-to-date picture.

The Hybrid Harms Hypothesis states that repeated spike antigenic exposure via mRNA vaccination may interact with either a previous or subsequent coronavirus infection due to the longterm persistence of spike protein in the body. This interaction results in an amplification of “spikeopathy”, manifesting as chronic immunotoxicity, hyper and persistent inflammation, immune dysregulation, and diverse pathological sequelae, including many disease and disability events that have been associated with both the COVID-19 vaccinations and coronavirus infections.

The Hybrid Harms Hypothesis is distinguished by five features. Merely a few points are quoted below.


1. The COVID-19 mRNA product’s three-pronged toxic payload.

  • The spike protein itself has potentially toxic effects and “can damage endothelial cells by downregulating ACE2 and consequently inhibiting mitochondrial function”.

  • The ionizable lipids of the lipid nanoparticle (LNP) delivery system “can stimulate the NLRP3 inflammasome and toll-like receptor (TLR) pathways, including TLR4, which has been linked to cancer progression”.

  • DNA impurities, such as the fragments of plasmid cDNA coding for SV40, can disrupt immune function and cause inflammation.


2. Whole-body biodistribution.

  • The spike protein goes throughout the entire body, including the heart, liver, spleen, ovaries, the nervous system and can even cross the blood-brain barrier.

  • Researchers found a “surge in the reporting of otherwise-rare prion diseases beginning in 2021, with initial symptoms appearing within an average of 11.38 days following the gene-based COVID-19 injections”.


3. Prolonged spike antigen exposure.

  • Initially, spike proteins were detected up to 4–8 weeks post-vaccination, longer than the initially claimed 1–2 weeks.

  • However, in a Japanese study of hemorrhagic stroke patients, “spike protein was found in cerebral arteries up to 17 months”. Another study found “post-vaccination levels persisting for 23.6 months (709 days)”.


4. Multiple exposures.

  • “T-cell responses against SARS-CoV-2 were significantly reduced one month following the first and second booster doses of the COVID-19 mRNA vaccine. This IgG4 class switch is also linked to the reduced T-cell response after three to four doses of the COVID-19 mRNA vaccine.”


5. Natural infection with overlapping vaccination.

  • The combination of natural infection and vaccination has been observed to cause immunologic changes, including hyperinflammation, autoimmunity, lymphopenia, and type I interferon suppression.

  • “Intriguingly, COVID-19 mRNA vaccinations have been shown to induce autoantibodies against type I interferons in healthy individuals. In both the infection and injection scenarios, the effect would be to suppress antiviral and anticancer immune responses.”


The paper discusses the usual observations of waning immunity, breakthrough infection, cardiovascular and other adverse events (AEs), excess mortality, and Post-Acute Sequelae of COVID-19 (PASC), also referred to as “long COVID”. Merely a few observations are reproduced below.


Regarding COVID-19 deaths after the vaccination rollout, some researchers

…observed a striking rise in COVID-19 deaths in tandem with vaccination coverage, from 43.3% in Africa to 1275% in the Western Pacific. Europe and the Americas comprised over 70% of global COVID-19 deaths despite high vaccination coverage. … Throughout Africa, where mRNA vaccination coverage has been relatively low, COVID-19-related morbidity and mortality rates have been much lower when compared with figures from other continents. By October 2023, the 55 African countries (population: >1.4 billion) reported a COVID-19 mortality rate approximately 4.5 times lower than the U.S. (population: ~330 million), despite minimal public health mandates and far lower vaccination rates.

Generally, and to put it simply, the excess mortality waves cannot be explained by the Omicron outbreaks alone in the most vaccinated countries.


As for PASC or so-called long COVID,

…unvaccinated individuals who had been exposed to Omicron showed the lowest PASC incidence, with previous Omicron infection being strongly associated with a lower PASC risk (OR 0.14, 95% CI 0.07; 0.25). No lowering of PASC risk was seen with the COVID-19 mRNA vaccinations.

In a South Korean study involving 3.4 million people who had received one or more COVID-19 mRNA vaccinations from February 2021 to March 2022, it was found that

…COVID-19 mRNA recipients infected by SARS-CoV-2 showed a nearly four-fold higher heart disease risk than uninfected mRNA recipients (adjusted HR, 3.56; 95% CI, 1.15-11.04), and younger mRNA recipients had a higher heart disease risk compared to older individuals. Contracting COVID-19 at any time was among the significant covariates that increased the cardiac risk following the mRNA vaccinations.

Not all studies support the Hybrid Harms Hypothesis but the authors point out that these studies did not necessarily correctly classify vaccination status. For example, an individual who suffered an AE within 14 days of receiving their first dose may be classified as “unvaccinated”.


This not only lowers the number of a given condition attributed to the vaccinated but also misattributes said condition to the truly unvaccinated.

Whether or not this is being done deliberately, the miscategorization serves to (a) reinforce the “safe and effective” narrative, thereby ensuring more pharmaceutical industry funding of mRNA vaccination and PASC research, and (b) motivate the policymakers, commentators, and the general public to continue to embrace the vaccinations.

In short, the combination of the so-called vaccine with natural infection may explain the “manifestation and/or persistence of serious AEs in previously vaccinated individuals”.


Figure 2: Central figure, 5 features of Hybrid Harms Hypothesis.
Figure 2: Central figure, 5 features of Hybrid Harms Hypothesis.

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