‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA
Abstract
:1. Introduction
2. COVID-19 Modelling Versus Real-World Data
“Failure in epidemic forecasting is an old problem. In fact, it is surprising that epidemic forecasting has retained much credibility among decision-makers, given its dubious track record. Modelling for swine flu predicted 3100–65,000 deaths in the UK (https://www.theguardian.com/uk/2009/jul/16/swine-flu-cases-rise-britain. (Accessed on 2 June 2020). Eventually, 457 deaths occurred (UK government, 2009)”.[16] (p. 425)
“Despite these obvious failures, [COVID-19] epidemic forecasting continued to thrive, perhaps because vastly erroneous predictions typically lacked serious consequences… Upon acquiring solid evidence about the epidemiological features of new outbreaks, implausible, exaggerated forecasts (Ioannidis, 2020d) should be abandoned. Otherwise, they may cause more harm than the virus itself”.[16] (p. 428)
3. Correspondence between TGA and Australian Senator Rennick
“There is some confusion around the biochemistry and immunology here. Higher translation and expression rate is not associated with pathogenicity, rather it indicates better antigen (spike protein) expression. The expressed spike protein is not a pathogen and is not infectious. The spike protein is only one component of the coronavirus. It serves as an antigen to induce humoral and cellular immune responses against SARS-CoV-2 virus”.[24]
4. Narrative Review Methodology
Key Points
- Highly safe and effective vaccines are central to combat infectious disease epidemics/pandemics.
- SARS-CoV-2 spike protein is pathogenic, whether from the virus or created from genetic code in mRNA and adenovectorDNA vaccines.
- Biodistribution rodent study data show lipid nanoparticles carry mRNA to all organs and cross blood-brain and blood-placenta barriers. Some of these tissues are likely to be impervious to viral infection; therefore, the biohazard is particularly from vaccination.
- Lipid-nanoparticles have inflammatory properties.
- The modification of mRNA with N1-methylpseudouridine for increased stability leads to the production of spike proteins for months. It is uncertain how many cells and from which organs mRNA spike proteins are produced, and therefore, the exact effective dose delivered per vaccine vial is unknown.
- The long-term fate of mRNA within cells is currently unknown.
- The mRNA and adenovectorDNA vaccines act as ‘synthetic viruses’.
- In the young and healthy, and even in many older individuals with vulnerable comorbidities, the encoding-based COVID-19 vaccines will likely transfect a far more diverse set of tissues than infection by the virus itself.
- Evidence suggests reverse transcription of mRNA into a DNA copy is possible. This further suggests the possibility of intergenerational transmission if germline cells incorporate the DNA copy into the host genome.
- Production of foreign proteins such as spike protein on cell surfaces can induce autoimmune responses and tissue damage. This has profoundly negative implications for any future mRNA-based drug or vaccine.
- The spike protein exerts its pathophysiological effects (‘spikeopathy’) via several mechanisms that lead to inflammation, thrombogenesis, and endotheliitis-related tissue damage and prion-related dysregulation.
- Interaction of the vaccine-encoded spike protein with ACE-2, P53 and BRCA1 suggests a wide range of possible biological interference with oncological potential.
- Adverse event data from official pharmacovigilance databases, an FDA-Pfizer report obtained via FOI, show high rates and multiple organ systems affected: primarily neurological, cardiovascular, and reproductive.
- Pfizer and Moderna mRNA COVID-19 vaccines’ clinical trial data independently interpreted has been peer-review and published to show an unfavourable risk/benefit, especially in the non-elderly. The risks for children clearly outweigh the benefits.
- Repeated COVID-19 vaccine booster doses appear to induce tolerance and may contribute to recurrent COVID-19 infection and ‘long COVID’.
- The SARS-CoV-2 pandemic has revealed deficiencies in public health and medicines regulatory agencies.
- A root cause analysis is needed for what now appears a rushed response to an alarming infectious disease pandemic.
- Treatment modalities for ‘spikeopathy’-related pathology in many organ systems, require urgent research and provision to millions of sufferers of long-term COVID-19 vaccine injuries.
5. Structure of SARS-CoV-2 Spike Protein
5.1. Does the Vaccine Produced Spike Protein Have Protective Closed RBDs?
5.2. Toxin-Like Domain in the RBD
6. Reasons for Concern: Pharmacodynamic, Pharmacokinetic, and Pathophysiological
6.1. Gene-Based Vaccines Are Novel Experimental Technology
6.2. Wide Distribution of Lipid-Nanoparticle
“The duration and kinetics of transgene expression are affected by the pharmacokinetics and biodistribution of the delivery systems. The pharmacokinetic-pharmacodynamic relationship of mRNA-LNPs is highly complex, making the prediction of gene expression and efficacy (pharmacodynamics) unlikely just based on LNP exposures in tissue (pharmacokinetics)”.[46] (pp. 112–113)
6.3. Long-lasting Pseudouridine mRNA
“mRNA COVID-19 vaccination might induce persistent VZV reactivation through perturbing the immune system, although it remained elusive whether the expressed spike protein played a pathogenic role”.[58] (abstract)
6.4. Nanoparticle Toxicology
6.5. Lipid-Nanoparticles Are Pro-Inflammatory
6.6. Novavax COVID-19 Vaccine Toxicity and Novel Lipid-Nanoparticle Technology
6.7. AstraZeneca COVID-19 Vaccine Biodistribution Data
“The biodistribution of AZD1222 following intramuscular administration is expected to be similar to that of AdCh63, confined to the site of injection and draining lymph nodes”.[75] (p. 13)
“The highest levels of AZD1222 vector DNA (103 to 107 copies/µg DNA) were observed in the intramuscular administration sites and sciatic nerve (close proximity to the administration sites) on Day 2. Lower levels of AZD1222 vector DNA (<LLOQ to 104 copies/μg DNA) were observed in the bone marrow, liver, spleen and lung on Day 2. The levels of AZD1222 and the number of tissues with detectable levels of AZD1222 vector DNA decreased from Day 2 to 29, indicating elimination”.[6] (p. 14)
“SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine are probably involved in the disease process.”
6.8. Traditional COVID-19 Vaccines Not Contributing High Adverse Event Reports
6.9. Autoimmune Risk of Foreign Antigens Presented by the Body’s Own Cells
6.10. Pathophysiology of Virus and Vaccine Spike Protein
- Binding to ACE-2 receptors as a “potential trigger for platelet aggregation, thrombosis and inflammation, as well as for hypertension and other cardiovascular disease”.
- Disruption of CD147 transmembrane glycoprotein which interferes with cardiac pericyte and erythrocyte function may result in myocarditis, haemolytic anaemia, blood hyperviscosity, and possibly neurodegenerative processes.
- Binding to Toll-like receptors 2 and 4 (TLR2, TLR4), with theoretical pathogenic effects via increased inflammatory cytokine cascades, due to (1) activation of Nuclear Factor kappa B (NF-κB pathway) and deficient macrophage immune function via TLR2, and (2) lung damage, myocarditis and multiorgan injury via TLR4, that had yet to be properly investigated by the world’s research community.
- Binding to the high affinity oestrogen receptor alpha (ER alpha) is possibly responsible for the menstrual irregularities commonly observed after COVID-19 vaccination and raising concerns of potential involvement in breast cancer.
- Spike protein S2 subunit specifically interacts with proteins p53 BP1 and BRCA1. The p53 BP1 is a well-established tumour suppressor; the BRCA1 is frequently mutated both in breast cancer and in prostate cancer [87].
“The pharmacokinetics of injection are different from an infection; 30–100 µg per injection (90–300 µg for those boosted) of Spike mRNA equates to 13 trillion to 40 trillion mRNA molecules injected in a few seconds with each injection. The pharmacokinetics of this bolus injection differs from that of viral replication that occurs over the course of a few days. If each of these mRNAs can produce 10–100 spike proteins and you have 30–40 trillion cells, there may be a far greater systemic quantity and a much longer duration of spike protein exposure through the vaccination route than natural infection”.[91] (p.12)
6.11. Disruption of the Nicotinic Cholinergic Anti-Inflammatory Pathway
7. Evidence of ‘Spikeopathy’—Spike Protein Pathogenicity
7.1. Cardiovascular Pathogenesis
7.1.1. Myocarditis and Pericarditis
“Before the COVID-19 pandemic, the estimated global incidence of myocarditis was 1 to 10 cases per 100,000 persons per year (12). The highest risk was among people between 20 and 40 years of age and among men; 6.1 cases per 100,000 men and 4.4 cases per 100,000 women. The increased use of cardiac MRI has led to a gradual rise in the reported incidence of myocarditis in the United States, from 9.5 to 14.4 cases per 100,000”.[108] (p. 1488)
“Even apparently mild episodes of myocarditis may lead to long-term sequelae, such as arrhythmias. … the majority of cases of myocarditis and/or pericarditis after mRNA COVID-19 vaccines (both Pfizer and Moderna) analysed to date occurred in older adolescents and young adults (aged 16 to 30 years), with the highest risk in younger males within days after dose 2”.[118] (p. 8)
7.1.2. Thrombotic Effects of Spike Proteins
“Free-floating Spike proteins released by the destroyed cells previously targeted by vaccines may interact with ACE-2 of other cells, thereby promoting ACE-2 internalisation and degradation (16,79). This mechanism may enhance the imbalance between Ang-II overactivity and Ang-1-7 deficiency through the loss of ACE-2 receptor activity, which may contribute to triggering inflammation, thrombosis, an increase in BP, and other adverse reactions (“Spike effect” of COVID-19 vaccines) (80,81). Moreover, the detrimental effects of other angiotensinases (POP and PRCP) deficiency on BP, thrombosis and inflammation are well supported”.[120] (p. 24)
“The relative deficiency of POP and PRCP among young and healthy subjects does not counterbalance ACE-2 internalisation, downregulation and malfunction due to free-floating Spike protein interactions, resulting in an increased risk of Ang-II accumulation, and adverse reactions (“Spike effect” of COVID-19 vaccines)”.[120] (p. 26)
“SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates”.[1] (abstract)
7.1.3. Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)
7.2. Autoimmune Disease
“Gut and barrier proteins, gastrointestinal system cells, thyroid, nervous system, heart, joint, skin, muscle, mitochondria, and liver diseases”.[9] (p. 5)
“The most common disease associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes”.[139] (abstract)
“Autoimmune reaction in the uveal tissue via molecular mimicry as a result of an adaptive humoral and poly-specific cellular immune response against epitopes may be the potential mechanism for post-vaccine uveitis in this patient”.(p. 1034)
“The pathogenic mechanisms by which mRNA vaccination triggers the development of autoimmune disease remains unclear. mRNA vaccination triggers potential cross-reactivity between antibodies against the spike protein and self-antigens and may also activate immune responses, leading to the production of interferon I and other pro-inflammatory cytokines and chemokines”.[148] (p. 3)
7.3. Neurological Disorders
7.3.1. Neurovascular and Neuroimmunological Aspects
“Induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-κB and p38 MAPK, possibly as a result of TLR4 activation.”[174] (Abstract, p. 445)
“Activation of BV-2 microglia by S1 resulted in the increased release of TNF-α, IL-6 and IL-1β, which are hallmarks of neuroinflammation. Activation of neuroinflammatory processes by the spike S1 protein was further confirmed by results showing increased iNOS-mediated production of NO by the protein in microglia. Elevated iNOS/NO has been previously linked to a wide range of CNS disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and migraine”.[174] (p. 452–453)
7.3.2. Prion Formation and Neurodegenerative Effects
- Spike-induced endotheliitis disturbs the blood-brain barrier and exacerbates Alzheimer’s disease via the interaction of the spike protein with amyloid β or hyperphosphorylated tau [164].
- Studies have shown that autoantibodies in the globular C-terminal domain can cause an aggressive form of Creutzfeldt Jakob Disease (CJD) by interfering with the transport of the prion protein into the endoplasmic reticulum [218].
- Cells that take up mRNA from the lipid nanoparticles in mRNA vaccines package up some of the mRNAs, together with the ionizable cationic lipids, into small lipid particles released as exosomes that can be shipped around the body [59,221]. For example, an immune cell in the spleen could ship intact mRNA code for the spike protein to the brain along the vagus nerve, whereupon a neuron or microglial cell could begin to synthesise spike protein.
- Micro RNA (miRNA) are small bits of active RNA code, capable of active control of cell function, including embryogenesis and apoptosis. miR-146a is found in exosomes released by immune cells and is on the list of miRNAs whose expression levels are altered in association with COVID-19 [222]. Exosomes that reach the brain stem deliver not only spike protein but potentially also intact mRNA and miRNA molecules, including miR-146a which is associated with both viral infection and prion diseases in the brain [223,224].
- Spike protein itself induces sharp TNF-α upregulation and causes cognitive issues which could indicate that it upregulates prion protein (PrP) expression in the brain. An increase in prion glycoprotein (PrPC) numbers can lead to prion conformation misfolding and generate prions and prion-related diseases [225,226].
- Spike protein has been shown to induce senescence in transfected cells [227]. Further, it has been proposed that the mRNA COVID-19 vaccines can induce premature senescence via syncytia formation in exposed immune cells, due primarily to their lipid content (ionizable lipids, cholesterol and the phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)) [228]. In vitro molecular studies show that macromolecular crowding can facilitate the conversion of native PrP into the neurotoxic soluble β oligomer configuration [229].
7.3.3. Dysautonomia
7.4. Carcinogenic Effects
7.5. Biopsy and Autopsy Evidence of Spikeopathy
“Cardiac disease in fatal COVID-19 is associated with viral spike protein, but not the infectious virus. The viral spike protein is endocytosed in interstitial macrophages and induces myocarditis. The histological findings show perivascular oedema, endothelial cell damage, and microthrombi”.[244] (highlights, p. 1)
“Yes, that is the finding that we have now been able to collect using special methods. This means that we are actually certain that in this case, we can still detect this toxin in the vessel walls 122 days after the vaccination. It is also clear that this is the causal factor for this damage.What’s not clear to me at the moment is whether it’s just deposited there or whether these cells actually produce the spike protein, as they are told to do by the mRNA, so to speak.”
“Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall”.[7] (abstract)
8. Discussion
9. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Zhang, S.; Liu, Y.; Wang, X.; Yang, L.; Li, H.; Wang, Y.; Liu, M.; Zhao, X.; Xie, Y.; Yang, Y.; et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J. Hematol. Oncol. 2020, 13, 120. [Google Scholar] [CrossRef] [PubMed]
- Solis, O.; Beccari, A.R.; Iaconis, D.; Talarico, C.; Ruiz-Bedoya, C.A.; Nwachukwu, J.C.; Cimini, A.; Castelli, V.; Bertini, R.; Montopoli, M.; et al. The SARS-CoV-2 spike protein binds and modulates estrogen receptors. Sci. Adv. 2022, 8, eadd4150. [Google Scholar] [CrossRef] [PubMed]
- Kiaie, S.H.; Majidi Zolbanin, N.; Ahmadi, A.; Bagherifar, R.; Valizadeh, H.; Kashanchi, F.; Jafari, R. Recent advances in mRNA-LNP therapeutics: Immunological and pharmacological aspects. J. Nanobiotechnol. 2022, 20, 276. [Google Scholar] [CrossRef]
- Kariko, K.; Muramatsu, H.; Welsh, F.A.; Ludwig, J.; Kato, H.; Akira, S.; Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 2008, 16, 1833–1840. [Google Scholar] [CrossRef]
- Therapeutic Goods Administration (TGA) FOI Reply 2389-6, p.45. Nonclinical Evaluation Report: BNT162b2 [mRNA] COVID-19 Vaccine (COMIRNATYTM). Submission No: PM-2020-05461-1-2. Sponsor: Pfizer Australia Pty Ltd. Australian Government Department of Health and Aged Care: 2021; FOI reply 2389-6. Available online: https://www.tga.gov.au/sites/default/files/foi-2389-06.pdf (accessed on 7 April 2023).
- AstraZeneca. 2.4 Nonclinical Overview AZD1222: Doc ID-004493554; MHRA: 2022-10-24-IR0751D 2021. Available online: https://icandecide.org/wp-content/uploads/2022/11/2022-10-24-IR0751D_Production_MHRA_000001-000166-166-pages.pdf (accessed on 12 July 2023).
- Geeraerts, T.; Guilbeau-Frugier, C.; Garcia, C.; Memier, V.; Raposo, N.; Bonneville, F.; Gales, C.; Darcourt, J.; Voisin, S.; Ribes, A.; et al. Immunohistologic features of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia. Neurol. Neuroimmunol. Neuroinflamm. 2023, 10, e200127. [Google Scholar] [CrossRef] [PubMed]
- Lyons-Weiler, J. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity. J. Transl. Autoimmun. 2020, 3, 100051. [Google Scholar] [CrossRef] [PubMed]
- Vojdani, A.; Vojdani, E.; Kharrazian, D. Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases. Front. Immunol. 2021, 11, 617089. [Google Scholar] [CrossRef]
- Reyna-Villasmil, E.; Caponcello, M.G.; Maldonado, N.; Olivares, P.; Caroccia, N.; Bonazzetti, C.; Tazza, B.; Carrara, E.; Giannella, M.; Tacconelli, E.; et al. Association of Patients’ Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis. Biomedicines 2022, 10, 2437. [Google Scholar] [CrossRef]
- Verity, R.; Okell, L.C.; Dorigatti, I.; Winskill, P.; Whittaker, C.; Imai, N.; Cuomo-Dannenburg, G.; Thompson, H.; Walker, P.G.T.; Fu, H.; et al. Estimates of the severity of coronavirus disease 2019: A model-based analysis. Lancet Infect. Dis. 2020, 20, 669–677. [Google Scholar] [CrossRef]
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
- RMIT Fact Check. Did Pfizer Make a ‘Scandalous’ Admission to the European Parliament about Its COVID-19 Vaccine? ABC News. 2022. Available online: https://abc.net.au/news/2022-10-21/fact-check-pfizer-admission-transmission-european-parliament/101556606 (accessed on 6 July 2023).
- Watson, O.J.; Barnsley, G.; Toor, J.; Hogan, A.B.; Winskill, P.; Ghani, A.C. Global impact of the first year of COVID-19 vaccination: A mathematical modelling study. Lancet Infect. Dis. 2022, 22, 1293–1302. [Google Scholar] [CrossRef] [PubMed]
- Roussel, Y.; Giraud-Gatineau, A.; Jimeno, M.T.; Rolain, J.M.; Zandotti, C.; Colson, P.; Raoult, D. SARS-CoV-2: Fear versus data. Int. J. Antimicrob. Agents 2020, 55, 105947. [Google Scholar] [CrossRef] [PubMed]
- Ioannidis, J.P.A.; Cripps, S.; Tanner, M.A. Forecasting for COVID-19 has failed. Int. J. Forecast. 2022, 38, 423–438. [Google Scholar] [CrossRef]
- Rid, A.; Lipsitch, M.; Miller, F.G. The Ethics of Continuing Placebo in SARS-CoV-2 Vaccine Trials. JAMA 2021, 325, 219–220. [Google Scholar] [CrossRef]
- WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Evaluation; Krause, P.R.; Fleming, T.R.; Longini, I.M.; Peto, R.; Beral, V.; Bhargava, B.; Cravioto, A.; Cramer, J.P.; Ellenberg, S.S.; et al. Placebo-Controlled Trials of Covid-19 Vaccines—Why We Still Need Them. N. Engl. J. Med. 2021, 384, e2. [Google Scholar] [CrossRef] [PubMed]
- Control Group Cooperative. The Covid Vaccine Study. 2021. Available online: https://www.vcgwiki.com/the-covid-vaccine-study (accessed on 3 July 2023).
- Verkerk, R.; Kathrada, N.; Plothe, C.; Lindley, K. Self-selected COVID-19 “unvaccinated” cohort reports favorable health outcomes and unjustified discrimination in global survey. Int. J. Vaccine Theory Pract. Res. 2022, 2, 321–354. [Google Scholar] [CrossRef]
- NSW Health. NSW Respiratory Surveillance Report—Week Ending 31 December 2022. 2022. Available online: https://www.health.nsw.gov.au/Infectious/covid-19/Documents/weekly-covid-overview-20221231.pdf (accessed on 10 July 2023).
- Therapeutic Goods Administration (TGA). COVID-19 vaccines regulatory status. Australian Government Department of Health and Aged Care: Tga.gov.au. 2023. Available online: https://www.tga.gov.au/products/covid-19/covid-19-vaccines/covid-19-vaccine-provisional-registrations (accessed on 7 April 2023).
- Therapeutic Goods Administration (TGA). TGA provisionally approves Novavax (Biocelect Pty Ltd’s COVID-19 vaccine NUVAXOVID. Australian Government Department of Health and Aged Care: Tga.gov.au. 2023. Available online: https://www.tga.gov.au/news/media-releases/tga-provisionally-approves-novavax-biocelect-pty-ltds-covid-19-vaccine-nuvaxovid (accessed on 7 April 2023).
- Senate Committee: Community Affairs Committee. Answers to Questions on Notice, Outcome: 1—Health Policy, Access and Support, 2022–2023 Budget Estimates October and November; Australian Federal Parliament: Canberra, Australia, 2022. [Google Scholar]
- Kuba, K.; Imai, Y.; Rao, S.; Gao, H.; Guo, F.; Guan, B.; Huan, Y.; Yang, P.; Zhang, Y.; Deng, W.; et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 2005, 11, 875–879. [Google Scholar] [CrossRef]
- Wrapp, D.; Wang, N.; Corbett, K.S.; Goldsmith, J.A.; Hsieh, C.L.; Abiona, O.; Graham, B.S.; McLellan, J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020, 367, 1260–1263. [Google Scholar] [CrossRef] [PubMed]
- Cuffari, B. What are Spike Proteins? News-Medical.Net. 2021. Available online: https://www.news-medical.net/health/What-are-Spike-Proteins.aspx (accessed on 26 April 2023).
- Carnell, G.W.; Ciazynska, K.A.; Wells, D.A.; Xiong, X.; Aguinam, E.T.; McLaughlin, S.H.; Mallery, D.; Ebrahimi, S.; Ceron-Gutierrez, L.; Asbach, B.; et al. SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses. J. Virol. 2021, 95, e0020321. [Google Scholar] [CrossRef]
- Seneff, S.; Kyriakopoulos, A.M.; Nigh, G.; McCullough, P.A. A Potential Role of the Spike Protein in Neurodegenerative Diseases: A Narrative Review. Cureus 2023, 15, e34872. [Google Scholar] [CrossRef]
- Changeux, J.P.; Amoura, Z.; Rey, F.A.; Miyara, M. A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications. Comptes Rendus Biol. 2020, 343, 33–39. [Google Scholar] [CrossRef] [PubMed]
- Nirthanan, S. Snake three-finger α-neurotoxins and nicotinic acetylcholine receptors: Molecules, mechanisms and medicine. Biochem. Pharmacol. 2020, 181, 114168. [Google Scholar] [CrossRef] [PubMed]
- Farsalinos, K.; Niaura, R.; Le Houezec, J.; Barbouni, A.; Tsatsakis, A.; Kouretas, D.; Vantarakis, A.; Poulas, K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol. Rep. 2020, 7, 658–663. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, B.C.V.; Weber, L.; Hueffer, K.; Weltzin, M.M. SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors. J. Biol. Chem. 2023, 299, 104707. [Google Scholar] [CrossRef]
- ACROBiosystems. An Overview of Different COVID-19 Vaccines. ACROBiosystems Insights, 2021. An Overview of Different COVID-19 Vaccines—ACROBiosystems. Available online: https://www.acrobiosystems.com/A1374-An-Overview-of-Different-COVID-19-Vaccines.html (accessed on 7 April 2023).
- Wikipedia. List of COVID-19 vaccine authorizations. 2023. Available online: https://en.wikipedia.org/wiki/List_of_COVID-19_vaccine_authorizations (accessed on 7 April 2023).
- U.S. Food and Drug Administration (FDA). FDA News Release: FDA Approves First-of-Its Kind Targeted RNA-Based Therapy to Treat a Rare Disease. FDA Newsroom FDA.gov.au. 2018. Available online: https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-targeted-rna-based-therapy-treat-rare-disease (accessed on 7 April 2023).
- Dolgin, E. The tangled history of mRNA vaccines. Nature 2021, 597, 318–324. [Google Scholar] [CrossRef]
- McCann, N.; O’Connor, D.; Lambe, T.; Pollard, A.J. Viral vector vaccines. Curr. Opin. Immunol. 2022, 77, 102210. [Google Scholar] [CrossRef]
- Altman, P.M.; Rowe, J.; Hoy, W.; Brady, G.; Lefringhausen, A.; Cosford, R.; Wauchope, B. Did National Security Imperatives Compromise COVID-19 Vaccine Safety? Trial Site News. 2022. Available online: https://www.trialsitenews.com/a/did-national-security-imperatives-compromise-covid-19-vaccine-safety-adfea242 (accessed on 9 June 2023).
- Lalani, H.S.; Nagar, S.; Sarpatwari, A.; Barenie, R.E.; Avorn, J.; Rome, B.N.; Kesselheim, A.S. US public investment in development of mRNA covid-19 vaccines: Retrospective cohort study. BMJ 2023, 380, e073747. [Google Scholar] [CrossRef] [PubMed]
- McCullough, P. America’s long, expensive, and deadly love affair with mRNA. In Courageous Discourse, Substack.com: 2023. Available online: https://petermcculloughmd.substack.com/p/americas-long-expensive-and-deadly (accessed on 15 March 2023).
- Turni, C.; Lefringhausen, A. Covid-19 vaccines—An Australian Review. J. Clin. Exp. Immunol. 2022, 7, 491–508. [Google Scholar]
- Ndeupen, S.; Qin, Z.; Jacobsen, S.; Bouteau, A.; Estanbouli, H.; Igyártó, B.Z. The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience 2021, 24, 103479. [Google Scholar] [CrossRef]
- Wick, P.; Malek, A.; Manser, P.; Meili, D.; Maeder-Althaus, X.; Diener, L.; Diener, P.A.; Zisch, A.; Krug, H.F.; von Mandach, U. Barrier capacity of human placenta for nanosized materials. Environ. Health Perspect. 2010, 118, 432–436. [Google Scholar] [CrossRef]
- Zhou, Y.; Peng, Z.; Seven, E.S.; Leblanc, R.M. Crossing the blood-brain barrier with nanoparticles. J. Control Release 2018, 270, 290–303. [Google Scholar] [CrossRef]
- Japanese Pharmaceuticals and Medical Devices Agency (PMDA). SARS-CoV-2 mRNA Vaccine (BNT162, PF-07302048). 2021. Available online: https://www.pmda.go.jp/drugs/2021/P20210212001/672212000_30300AMX00231_I100_1.pdf (accessed on 7 April 2023).
- Judicial Watch. Pfizer/BioNTech Study Found Lipid Nanoparticles Materials Outside Injection Site in Test Animals. judicialwatch.org. 2022. Available online: https://www.judicialwatch.org/nanoparticles-materials-outside-injection-site/ (accessed on 12 July 2023).
- Di, J.; Du, Z.; Wu, K.; Jin, S.; Wang, X.; Li, T.; Xu, Y. Biodistribution and Non-linear Gene Expression of mRNA LNPs Affected by Delivery Route and Particle Size. Pharm. Res. 2022, 39, 105–114. [Google Scholar] [CrossRef] [PubMed]
- Morais, P.; Adachi, H.; Yu, Y.T. The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Front. Cell. Dev. Biol. 2021, 9, 789427. [Google Scholar] [CrossRef] [PubMed]
- Fertig, T.E.; Chitoiu, L.; Marta, D.S.; Ionescu, V.S.; Cismasiu, V.B.; Radu, E.; Angheluta, G.; Dobre, M.; Serbanescu, A.; Hinescu, M.E.; et al. Vaccine mRNA can be detected in blood at 15 days post-vaccination. Biomedicines 2022, 10, 1538. [Google Scholar] [CrossRef] [PubMed]
- Castruita, J.A.S.; Schneider, U.V.; Mollerup, S.; Leineweber, T.D.; Weis, N.; Bukh, J.; Pedersen, M.S.; Westh, H. SARS-CoV-2 spike mRNA vaccine sequences circulate in blood up to 28 days after COVID-19 vaccination. APMIS 2023, 131, 128–132. [Google Scholar] [CrossRef]
- Ogata, A.F.; Cheng, C.-A.; Desjardins, M.; Senussi, Y.; Sherman, A.C.; Powell, M.; Novack, L.; Von, S.; Li, X.; Baden, L.R.; et al. Circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine antigen detected in the plasma of mRNA-1273 vaccine recipients. Clin. Infect. Dis. 2021, 74, 715–718. [Google Scholar] [CrossRef]
- Röltgen, K.; Nielsen, S.C.A.; Silva, O.; Younes, S.F.; Zaslavsky, M.; Costales, C.; Yang, F.; Wirz, O.F.; Solis, D.; Hoh, R.A.; et al. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell 2022, 185, 1025–1040.e14. [Google Scholar] [CrossRef]
- Yonker, L.M.; Swank, Z.; Bartsch, Y.C.; Burns, M.D.; Kane, A.; Boribong, B.P.; Davis, J.P.; Loiselle, M.; Novak, T.; Senussi, Y.; et al. Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis. Circulation 2023, 147, 867–876. [Google Scholar] [CrossRef]
- Jikomes, N. Pseudouridine, mRNA Vaccines & Spike Protein Persistence. In Mind & Matter with Nick Jikomes, mindandmatter.substack.com. 2022. Available online: https://mindandmatter.substack.com/p/pseudouridine-mrna-vaccines-and-spike (accessed on 7 April 2023).
- Yong, S.J. mRNA Vaccine Stays Active in the Body Longer than Expected, New Data Shows. But it isn’t Dangerous. In Microbial Instincts, Medium.com. 2022. Available online: https://medium.com/microbial-instincts/mrna-vaccine-stays-active-in-the-body-longer-than-expected-new-data-shows-but-it-isnt-harmful-aaa40544bc06 (accessed on 7 April 2023).
- Bansal, S.; Perincheri, S.; Fleming, T.; Poulson, C.; Brian, T.; Bremner, M.R.; Mohanakumar, T. Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer–BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines. J. Immunol. 2021, 207, 2405–2410. [Google Scholar] [CrossRef]
- Yamamoto, M.; Kase, M.; Sano, H.; Kamijima, R.; Sano, S. Persistent varicella zoster virus infection following mRNA COVID-19 vaccination was associated with the presence of encoded spike protein in the lesion. J. Cutan. Immunol. Allergy 2023, 6, 18–23. [Google Scholar] [CrossRef]
- Maugeri, M.; Nawaz, M.; Papadimitriou, A. Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells. Nat. Commun. 2019, 10, 4333. [Google Scholar] [CrossRef]
- Wang, R.; Huang, K. CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL 2 and TGF β by CD4+ T cells via the STAT5 signaling pathway. Mol. Med. Rep. 2020, 21, 2522–2532. [Google Scholar] [CrossRef] [PubMed]
- Segalla, G. Chemical-physical criticality and toxicological potential of lipid nanomaterials contained in a COVID-19 mRNA vaccine. Int. J. Vaccine Theory Pract. Res. Inj. Causes Treat. 2023, 3, 787–817. [Google Scholar] [CrossRef]
- European Parliament. Parliamentary question P-005690/2021: Excipients ALC-0315 and ALC-0159. Priority Question for Written Answer to the Commission, Rule 138, Guido Reil (ID); European Parliament Europarl.europa.eu 2021. Available online: https://www.europarl.europa.eu/doceo/document/P-9-2021-005690_EN.html (accessed on 4 June 2023).
- Bushmanova, S.V.; Ivanov, A.O.; Buyevich, Y.U. The effect of an electrolyte on phase separation in colloids. In Physica A: Statistical Mechanics and Its Applications; Elsevier: Amsterdam, The Netherlands, 1994; Volume 202, pp. 175–195. [Google Scholar]
- Poon, W.; Zhang, Y.N.; Ouyang, B.; Kingston, B.R.; Wu, J.L.Y.; Wilhelm, S.; Chan, W.C.W. Elimination Pathways of Nanoparticles. ACS Nano 2019, 13, 5785–5798. [Google Scholar] [CrossRef] [PubMed]
- Trougakos, I.P.; Terpos, E.; Alexopoulos, H.; Politou, M.; Paraskevis, D.; Scorilas, A.; Kastritis, E.; Andreakos, E.; Dimopoulos, M.A. COVID-19 mRNA vaccine-induced adverse effects: Unwinding the unknowns. Trends Mol. Med. 2022, 28, 800–802. [Google Scholar] [CrossRef]
- Halma, M.T.; Rose, J.; Lawrie, T. The novelty of mRNA viral vaccines and potential harms: A scoping review. J 2023, 6, 220–235. [Google Scholar] [CrossRef]
- Yamamoto, K. Adverse effects of Covid-19 vaccines and measures to prevent them. Virol. J. 2022, 19, 100. [Google Scholar] [CrossRef]
- Sahin, U.; Oehm, P.; Derhovanessian, E.; Jabulowsky, R.A.; Vormehr, M.; Gold, M.; Maurus, D.; Schwarck-Kokarakis, D.; Kuhn, A.N.; Omokoko, T.; et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 2020, 585, 107–112. [Google Scholar] [CrossRef]
- Doener, F.; Hong, H.S.; Meyer, I.; Tadjalli-Mehr, K.; Daehling, A.; Heidenreich, R.; Koch, S.D.; Fotin-Mleczek, M.; Gnad-Vogt, U. RNA-based adjuvant CV8102 enhances the immunogenicity of a licensed rabies vaccine in a first-in-human trial. Vaccine 2019, 37, 1819–1826. [Google Scholar] [CrossRef]
- Anttila, V.; Saraste, A.; Knuuti, J.; Jaakkola, P.; Hedman, M.; Svedlund, S.; Lagerström-Fermér, M.; Kjaer, M.; Jeppsson, A.; Gan, L.M. Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial. Mol. Ther. Methods Clin. Dev. 2020, 18, 464–472. [Google Scholar] [CrossRef]
- Crescioli, S.; Correa, I.; Karagiannis, P.; Davies, A.M.; Sutton, B.J.; Nestle, F.O.; Karagiannis, S.N. IgG4 Characteristics and Functions in Cancer Immunity. Curr. Allergy Asthma Rep. 2016, 16, 7. [Google Scholar] [CrossRef] [PubMed]
- Schlaudecker, E.P.; McNeal, M.M.; Dodd, C.N.; Ranz, J.B.; Steinhoff, M.C. Pregnancy modifies the antibody response to trivalent influenza immunization. J. Infect. Dis. 2012, 206, 1670–1673. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Lu, H.; Peng, L.; Zhou, J.; Wang, M.; Li, J.; Liu, Z.; Zhang, W.; Zhao, Y.; Zeng, X.; et al. The role of PD-1/PD-Ls in the pathogenesis of IgG4-related disease. Rheumatology 2022, 61, 815–825. [Google Scholar] [CrossRef] [PubMed]
- Medsafe. Alert Communication: Myocarditis and Pericarditis have been Reported with Nuvaxovid (Novavax COVID-19 vaccine). New Zealand Medicines and Medical Devices Safety Authority: Medsafe.govt.nz. 2022. Available online: https://www.medsafe.govt.nz/safety/Alerts/nuvaxovid-myocarditis.asp (accessed on 7 April 2023).
- AstraZeneca. 2.4 Nonclinical Overview AZD1222: Doc ID-004365565; MHRA: 2022-10-24-IR0751D 2020. Available online: https://icandecide.org/wp-content/uploads/2022/11/2022-10-24-IR0751D_Production_MHRA_000001-000166-166-pages.pdf (accessed on 12 July 2023).
- Biotech, B. Covaxin—India’s First Indigenous COVID-19 Vaccine. 2022. Available online: https://www.bharatbiotech.com/covaxin.html (accessed on 8 April 2023).
- Sinovac. Overview of CoronaVac. 2021. Available online: http://www.coronavac.cn/ (accessed on 8 April 2023).
- Vaxine. COVID-19 Project. 2022. Available online: https://vaxine.net/projects/ (accessed on 11 June 2023).
- CinnaGen. SpikoGen: Recombinant COVID-19 Vaccine. 2022. Available online: https://www.cinnagen.com/Product.aspx?t=2&l=1&Id=607 (accessed on 11 June 2023).
- Tabarsi, P.; Anjidani, N.; Shahpari, R.; Mardani, M.; Sabzvari, A.; Yazdani, B.; Roshanzamir, K.; Bayatani, B.; Taheri, A.; Petrovsky, N.; et al. Safety and immunogenicity of SpikoGen®, an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: A phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations. Clin. Microbiol. Infect. 2022, 28, 1263–1271. [Google Scholar] [CrossRef]
- Tabarsi, P.; Anjidani, N.; Shahpari, R.; Roshanzamir, K.; Fallah, N.; Andre, G.; Petrovsky, N.; Barati, S. Immunogenicity and safety of SpikoGen®, an adjuvanted recombinant SARS-CoV-2 spike protein vaccine as a homologous and heterologous booster vaccination: A randomized placebo-controlled trial. Immunology 2022, 167, 340–353. [Google Scholar] [CrossRef]
- Tabarsi, P.; Anjidani, N.; Shahpari, R.; Mardani, M.; Sabzvari, A.; Yazdani, B.; Kafi, H.; Fallah, N.; Ebrahimi, A.; Taheri, A.; et al. Evaluating the efficacy and safety of SpikoGen®, an Advax-CpG55.2-adjuvanted severe acute respiratory syndrome coronavirus 2 spike protein vaccine: A phase 3 randomized placebo-controlled trial. Clin. Microbiol. Infect. 2023, 29, 215–220. [Google Scholar] [CrossRef]
- Scendoni, R.; Cingolani, M. What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant? Diagn. Pathol. 2023, 18, 18. [Google Scholar] [CrossRef]
- Department of Health and Aged Care. Comirnaty (Pfizer). Australian Government. 2022. Available online: https://www.health.gov.au/our-work/covid-19-vaccines/our-vaccines/pfizer (accessed on 11 June 2023).
- Therapeutic Goods Administration (TGA). Moderna COVID-19 Bivalent (SPIKEVAX Bivalent Original/Omicron BA.4-5) Booster Dose Vaccine. Australian Government Department of Health and Aged Care. 2023. Available online: https://www.tga.gov.au/products/covid-19/covid-19-vaccines/covid-19-vaccine-provisional-registrations/moderna-covid-19-bivalent-spikevax-bivalent-originalomicron-ba4-5-booster-dose-vaccine (accessed on 11 June 2023).
- Cosentino, M.; Marino, F. Understanding the pharmacology of COVID-19 mRNA vaccines: Playing dice with the spike? Int. J. Mol. Sci. 2022, 23, 10881. [Google Scholar] [CrossRef]
- Singh, H.N.; Singh, A.B. S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor Protein p53 and BRCA: An In Silico Study. Transl. Oncol. 2020, 13, 100814. [Google Scholar] [CrossRef]
- Barreda, D.; Santiago, C.; Rodríguez, J.R.; Rodríguez, J.F.; Casasnovas, J.M.; Mérida, I.; Ávila-Flores, A. SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells. Cells 2021, 10, 3279. [Google Scholar] [CrossRef]
- Suzuki, Y.J.; Nikolaienko, S.I.; Dibrova, V.A.; Dibrova, Y.V.; Vasylyk, V.M.; Novikov, M.Y.; Shults, N.V.; Gychka, S.G. SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells. Vascul. Pharmacol. 2021, 137, 106823. [Google Scholar] [CrossRef] [PubMed]
- Colunga Biancatelli, R.M.L.; Solopov, P.A.; Sharlow, E.R.; Lazo, J.S.; Marik, P.E.; Catravas, J.D. The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2021, 321, L477–L484. [Google Scholar] [CrossRef]
- McKernan, K.; Kyriakopoulos, A.M.; McCullough, P.A. Differences in vaccine and SARS-CoV-2 replication derived mRNA: Implications for cell biology and future disease. OSF Preprints 2021. [Google Scholar] [CrossRef]
- Lei, Y.; Zhang, J.; Schiavon, C.R.; He, M.; Chen, L.; Shen, H.; Zhang, Y.; Yin, Q.; Cho, Y.; Andrade, L.; et al. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circ. Res. 2021, 128, 1323–1326. [Google Scholar] [CrossRef] [PubMed]
- Nadwa, E.H.; Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Elekhnawy, E.; Albogami, S.M.; Alorabi, M.; Batiha, G.E.; De Waard, M. Cholinergic dysfunction in COVID-19: Frantic search and hoping for the best. Naunyn Schmiedebergs Arch. Pharmacol. 2023, 396, 453–468. [Google Scholar] [CrossRef] [PubMed]
- Alexandris, N.; Lagoumintzis, G.; Chasapis, C.T.; Leonidas, D.D.; Papadopoulos, G.E.; Tzartos, S.J.; Tsatsakis, A.; Eliopoulos, E.; Poulas, K.; Farsalinos, K. Nicotinic cholinergic system and COVID-19: Toxicol. Rep. 2021, 8, 73–83. [Google Scholar] [CrossRef]
- Hollenhorst, M.I.; Krasteva-Christ, G. Nicotinic Acetylcholine Receptors in the Respiratory Tract. Molecules 2021, 26, 6097. [Google Scholar] [CrossRef]
- Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Qusti, S.; Alshammari, E.M.; Gyebi, G.A.; Batiha, G.E. Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm. ASN Neuro 2021, 13, 17590914211057635. [Google Scholar] [CrossRef]
- Patterson, B.K.; Seethamraju, H.; Dhody, K.; Corley, M.J.; Kazempour, K.; Lalezari, J.; Pang, A.P.S.; Sugai, C.; Mahyari, E.; Francisco, E.B.; et al. CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int. J. Infect. Dis. 2021, 103, 25–32. [Google Scholar] [CrossRef]
- Henrion-Caude, A. Spikopathy: The Pathology of the Spike Protein. Conference Presentation, General Assembly Meeting, World Council for Health. worldcouncilforhealth.org. 2021. Available online: https://worldcouncilforhealth.org/multimedia/alexandra-henrion-caude-france-spikopathy/ (accessed on 7 April 2023).
- Anderson, S. CBER Plans for Monitoring COVID-19 Vaccine Safety and Effectiveness. U.S. Food & Drug Administration (FDA): Vaccines and Related Biological Products Advisory Committee meeting. 2020. Available online: https://www.fda.gov/media/143557/download (accessed on 7 April 2023).
- React19. 3400+ COVID Vaccine Publications and Case Reports. 2022. Available online: https://react19.org/1250-covid-vaccine-reports/ (accessed on 11 June 2023).
- Avolio, E.; Carrabba, M.; Milligan, R.; Kavanagh Williamson, M.; Beltrami, A.P.; Gupta, K.; Elvers, K.T.; Gamez, M.; Foster, R.R.; Gillespie, K.; et al. The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: A potential non-infective mechanism of COVID-19 microvascular disease. Clin. Sci. 2021, 135, 2667–2689. [Google Scholar] [CrossRef]
- Cao, X.; Nguyen, V.; Tsai, J.; Gao, C.; Tian, Y.; Zhang, Y.; Carver, W.; Kiaris, H.; Cui, T.; Tan, W. The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice. Mol. Metab. 2023, 74, 101756. [Google Scholar] [CrossRef] [PubMed]
- Baumeier, C.; Aleshcheva, G.; Harms, D.; Gross, U.; Hamm, C.; Assmus, B.; Westenfeld, R.; Kelm, M.; Rammos, S.; Wenzel, P.; et al. Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series. Int. J. Mol. Sci. 2022, 23, 6940. [Google Scholar] [CrossRef] [PubMed]
- Barmada, A.; Klein, J.; Ramaswamy, A.; Brodsky, N.N.; Jaycox, J.R.; Sheikha, H.; Jones, K.M.; Habet, V.; Campbell, M.; Sumida, T.S.; et al. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis. Sci. Immunol. 2023, 8, eadh3455. [Google Scholar] [CrossRef]
- Wu, C.T.; Chin, S.C.; Chu, P.H. Acute Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccine: A Case Report and Literature Review. Front. Cardiovasc. Med. 2022, 9, 856991. [Google Scholar] [CrossRef] [PubMed]
- Sulemankhil, I.; Abdelrahman, M.; Negi, S.I. Temporal Association Between the COVID-19 Ad26.COV2.S Vaccine and Acute Myocarditis: A Case Report and Literature Review. Cardiovasc. Revasc. Med. 2022, 38, 117–123. [Google Scholar] [CrossRef]
- Olejniczak, M.; Schwartz, M.; Webber, E.; Shaffer, A.; Perry, T.E. Viral Myocarditis-Incidence, Diagnosis and Management. J. Cardiothorac. Vasc. Anesth. 2020, 34, 1591–1601. [Google Scholar] [CrossRef]
- Basso, C. Myocarditis. N. Engl. J. Med. 2022, 387, 1488–1500. [Google Scholar] [CrossRef]
- Simone, A.; Herald, J.; Chen, A.; Gulati, N.; Shen, A.Y.; Lewin, B.; Lee, M.S. Acute Myocarditis Following COVID-19 mRNA Vaccination in Adults Aged 18 Years or Older. JAMA Intern. Med. 2021, 181, 1668–1670. [Google Scholar] [CrossRef]
- Lane, S.; Yeomans, A.; Shakir, S. Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination. BMJ Open 2022, 12, e060425. [Google Scholar] [CrossRef]
- Naik, R. FDA: Summary Basis for Regulatory Action. fda.gov. 2021. Available online: https://www.fda.gov/media/151733/download (accessed on 8 November 2022).
- Tschöpe, C.; Ammirati, E.; Bozkurt, B.; Caforio, A.L.P.; Cooper, L.T.; Felix, S.B.; Hare, J.M.; Heidecker, B.; Heymans, S.; Hübner, N.; et al. Myocarditis and inflammatory cardiomyopathy: Current evidence and future directions. Nat. Rev. Cardiol. 2021, 18, 169–193. [Google Scholar] [CrossRef]
- Mansanguan, S.; Charunwatthana, P.; Piyaphanee, W.; Dechkhajorn, W.; Poolcharoen, A.; Mansanguan, C. Cardiovascular Manifestation of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents. Trop. Med. Infect. Dis. 2022, 7, 196. [Google Scholar] [CrossRef] [PubMed]
- Müller, C.; Buergin, N.; Lopez-Ayala, P.; Hirsiger, J.R.; Mueller, P.; Median, D.; Glarner, N.; Rumora, K.; Herrmann, T.; Koechlin, L.; et al. Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 Booster Vaccination. Eur. J. Heart Fail, 2023; accepted author manuscript. [Google Scholar] [CrossRef]
- Manno, E.C.; Amodio, D.; Cotugno, N.; Rossetti, C.; Giancotta, C.; Santilli, V.; Zangari, P.; Rotulo, G.A.; Villani, A.; Giglioni, E.; et al. Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination. Pediatr. Infect. Dis. J. 2023, 42, 166–171. [Google Scholar] [CrossRef] [PubMed]
- Dowd, E. Cause Unknown: The Epidemic of Sudden Deaths in 2021 and 2022; Children’s Health Defence: Washington, DC, USA, 2022. [Google Scholar]
- Dowd, E.; Nunes, Y.; Alegria, C. US Disability Data: Part 4—Relation with Excess Deaths. Bureau of Labor Statistics (BLS). Phinancetechnologies.com. 2022. Available online: https://phinancetechnologies.com/HumanityProjects/US%20Disabilities%20-%20Part4.htm (accessed on 8 November 2022).
- Therapeutic Goods Administration (TGA), FOI Reply 4093-02. Advisory Committee on Vaccines (ACV) Meeting 22, Minutes on item 2.1, BNT162b2 [mRNA] vaccine. 2021. Available online: https://www.tga.gov.au/sites/default/files/2023-03/foi-4093-02.pdf (accessed on 7 April 2023).
- Angeli, F.; Spanevello, A.; Reboldi, G.; Visca, D.; Verdecchia, P. SARS-CoV-2 vaccines: Lights and shadows. Eur. J. Intern. Med. 2021, 88, 1–8. [Google Scholar] [CrossRef]
- Angeli, F.; Reboldi, G.; Trapasso, M.; Zappa, M.; Spanevello, A.; Verdecchia, P. COVID-19, vaccines and deficiency of ACE2 and other angiotensinases. Closing the loop on the “Spike effect”. Eur. J. Intern. Med. 2022, 103, 23–28. [Google Scholar] [CrossRef]
- Kuhn, C.C.; Basnet, N.; Bodakuntla, S.; Alvarez-Brecht, P.; Nichols, S.; Martinez-Sanchez, A.; Agostini, L.; Soh, Y.M.; Takagi, J.; Biertümpfel, C.; et al. Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein. Nat. Commun. 2023, 14, 620. [Google Scholar] [CrossRef]
- Zheng, Y.; Zhao, J.; Li, J.; Guo, Z.; Sheng, J.; Ye, X.; Jin, G.; Wang, C.; Chai, W.; Yan, J.; et al. SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate. Int. J. Biol. Macromol. 2021, 193, 1124–1129. [Google Scholar] [CrossRef] [PubMed]
- Ryu, J.K.; Sozmen, E.G.; Dixit, K.; Montano, M.; Matsui, Y.; Liu, Y.; Helmy, E.; Deerinck, T.J.; Yan, Z.; Schuck, R.; et al. SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy. bioRxiv 2021. preprint. [Google Scholar] [CrossRef]
- Boschi, C.; Scheim, D.E.; Bancod, A.; Militello, M.; Bideau, M.L.; Colson, P.; Fantini, J.; Scola, B. SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects. Int. J. Mol. Sci. 2022, 23, 15480. [Google Scholar] [CrossRef]
- Purnell, M.C.; Skrinjar, T.J. Bioelectric Field Enhancement: The Influence on Membrane Potential and Cell Migration In Vitro. Adv. Wound Care 2016, 5, 539–545. [Google Scholar] [CrossRef]
- Purnell, M.C.; Skrinjar, T.J. The dielectrophoretic disassociation of chloride ions and the influence on diamagnetic anisotropy in cell membranes. Discov. Med. 2016, 22, 257–273. [Google Scholar]
- Papasimakis, N.; Fedotov, V.A.; Savinov, V.; Raybould, T.A.; Zheludev, N.I. Electromagnetic toroidal excitations in matter and free space. Nat. Mater. 2016, 15, 263–271. [Google Scholar] [CrossRef] [PubMed]
- Purnell, M.C.; Butawan, M.B.A.; Ramsey, R.D. Bio-field array: A dielectrophoretic electromagnetic toroidal excitation to restore and maintain the golden ratio in human erythrocytes. Physiol. Rep. 2018, 6, e13722. [Google Scholar] [CrossRef] [PubMed]
- Kooijman, S.; Meurs, I.; van der Stoep, M.; Habets, K.L.; Lammers, B.; Berbée, J.F.; Havekes, L.M.; van Eck, M.; Romijn, J.A.; Korporaal, S.J.; et al. Hematopoietic α7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis. J. Thromb. Haemost. 2015, 13, 126–135. [Google Scholar] [CrossRef] [PubMed]
- Li, J.X.; Wang, Y.H.; Bair, H.; Hsu, S.B.; Chen, C.; Wei, J.C.; Lin, C.J. Risk assessment of retinal vascular occlusion after COVID-19 vaccination. NPJ Vaccines 2023, 8, 64. [Google Scholar] [CrossRef]
- Herrera-Comoglio, R.; Lane, S. Vaccine-Induced Immune Thrombocytopenia and Thrombosis after the Sputnik V Vaccine. N. Engl. J. Med. 2022, 387, 1431–1432. [Google Scholar] [CrossRef] [PubMed]
- Buoninfante, A.; Andeweg, A.; Baker, A.T.; Borad, M.; Crawford, N.; Dogné, J.M.; Garcia-Azorin, D.; Greinacher, A.; Helfand, R.; Hviid, A.; et al. Understanding thrombosis with thrombocytopenia syndrome after COVID-19 vaccination. NPJ Vaccines 2022, 7, 141. [Google Scholar] [CrossRef]
- Leung, H.H.L.; Perdomo, J.; Ahmadi, Z.; Zhen, S.S.; Rashi, F.N.; Enjeti, A.; Ting, S.B.; Chong, J.J.H.; Chong, B.H. NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia. Nat. Commun. 2022, 13, 5206. [Google Scholar] [CrossRef]
- Greinacher, A.; Schönborn, L.; Siegerist, F.; Steil, L.; Palankar, R.; Handtke, S.; Reder, A.; Thiele, T.; Aurich, K.; Methling, K.; et al. Pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT). Seminars Hematol. 2022, 59, 97–107. [Google Scholar] [CrossRef]
- Talotta, R.; Robertson, E.S. Antiphospholipid antibodies and risk of poast-COVID-19 vaccination thrombophilia: The straw that breaks the camels’s back? Cytokine Growth Factor Rev. 2021, 60, 52–60. [Google Scholar] [CrossRef]
- Khavinson, V.; Terekhov, A.; Kormilets, D.; Maryanovich, A. Homology between SARS CoV-2 and human proteins. Sci. Rep. 2021, 11, 17199. [Google Scholar] [CrossRef]
- Kelleni, M. SARS-CoV-2 vaccination, autoimmunity, antibody dependent Covid-19 enhancement and other potential risks: Beneath the tip of the iceberg. Int. J. Pulm. Respir. Sci. 2021, 5, 555658. [Google Scholar] [CrossRef]
- Alqatari, S.; Ismail, M.; Hasan, M.; Bukhara, R.; Al Argan, R.; Alwaheed, A.; Alkhafaji, D.; Ahmed, S.; Hadhiah, K.; Alamri, T.; et al. Emergence of post COVID-19 vaccine autoimmune diseases: A single centre study. Infect. Drug Resist. 2023, 16, 1263–1278. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez, Y.; Rojas, M.; Beltran, S.; Polo, F.; Camacho-Dominguez, L.; Morales, S.D.; Gershwin, M.E.; Anaya, J.M. Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review. J. Autoimmun. 2022, 132, 102898. [Google Scholar] [CrossRef]
- Lansang, R.P.; Amdemichael, E.; Sajic, D. IgA pemphigus following COVID-19 vaccination: A case report. SAGE Open Med. Case Rep. 2023, 11, 2050313X231181022. [Google Scholar] [CrossRef]
- Minakawa, S.; Matsuzaki, Y.; Yao, S.; Sagara, C.; Akasaka, E.; Koga, H.; Ishii, N.; Hashimoto, T.; Sawamura, D. Case report: A case of epidermolysis bullosa acquisita with IgG and IgM anti-basement membrane zone antibodies relapsed after COVID-19 mRNA vaccination. Front. Med. 2023, 10, 1093827. [Google Scholar] [CrossRef]
- Makiyama, A.; Abe, Y.; Furusawa, H.; Kogami, M.; Ando, T.; Tada, K.; Onimaru, M.; Ishizu, A.; Yamaji, K.; Tamura, N. Polyarteritis nodosa diagnosed in a young male after COVID-19 vaccine: A case report. Mod. Rheumatol. Case Rep. 2023. [Google Scholar] [CrossRef] [PubMed]
- Takedani, K.; Notsu, M.; Ishiai, N.; Asami, Y.; Uchida, K.; Kanasaki, K. Graves’ disease after exposure to the SARS-CoV-2 vaccine: A case report and review of the literature. BMC Endocr. Disord. 2023, 23, 132. [Google Scholar] [CrossRef]
- Morimoto, N.; Mori, T.; Shioji, S.; Taguchi, T.; Watanabe, H.; Sakai, K.; Mori, K.; Yamamura, A.; Hanioka, A.; Akagi, Y.; et al. Rapidly progressive IgA nephropathy with membranoproliferative glomerulonephritis-like lesions in an elderly man following the third dose of an mRNA COVID-19 vaccine: A case report. BMC Nephrol. 2023, 24, 108. [Google Scholar] [CrossRef]
- Aochi, S.; Uehara, M.; Yamamoto, M. IgG4-related Disease Emerging after COVID-19 mRNA Vaccination. Intern. Med. 2023, 62, 1547–1551. [Google Scholar] [CrossRef]
- Cam, F.; Gok, G.; Celiker, H. Granulomatous anterior uveitis following mRNA-based COVID-19 vaccination: A case report. Indian J. Ophthalmol. 2023, 71, 1033–1035. [Google Scholar] [CrossRef]
- Yamamoto, M.; Keino, D.; Sumii, S.; Yokosuka, T.; Goto, H.; Inui, A.; Sogo, T.; Kawakami, M.; Tanaka, M.; Yanagimachi, M. Severe Hepatitis-associated Aplastic Anemia Following COVID-19 mRNA Vaccination. Intern. Med. 2023, 62, 1813–1816. [Google Scholar] [CrossRef] [PubMed]
- Talotta, R. Do COVID-19 RNA-based vaccines put at risk of immune-mediated diseases? In reply to “potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases”. Clin. Immunol. 2021, 224, 108665. [Google Scholar] [CrossRef]
- Irrgang, P.; Gerling, J.; Kocher, K.; Lapuente, D.; Steininger, P.; Habenicht, K.; Wytopil, M.; Beileke, S.; Schäfer, S.; Zhong, J.; et al. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Sci. Immunol. 2023, 8, eade2798. [Google Scholar] [CrossRef] [PubMed]
- Uversky, V.N.; Redwan, E.M.; Makis, W.; Rubio-Casillas, A. IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein. Vaccines 2023, 11, 991. [Google Scholar] [CrossRef]
- Patel, N.R.; Anzalone, M.L.; Buja, L.M.; Elghetany, M.T. Sudden cardiac death due to coronary artery involvement by IgG4-related disease: A rare, serious complication of a rare disease. Arch. Pathol. Lab. Med. 2014, 138, 833–836. [Google Scholar] [CrossRef]
- Gutierrez, P.S.; Schultz, T.; Siqueira, S.A.; de Figueiredo Borges, L. Sudden coronary death due to IgG4-related disease. Cardiovasc. Pathol. 2013, 22, 505–507. [Google Scholar] [CrossRef]
- Martín-Nares, E.; Saavedra-González, V.; Fagundo-Sierra, R.; Santinelli-Núñez, B.E.; Romero-Maceda, T.; Calderón-Vasquez, K.; Hernandez-Molina, G. Serum immunoglobulin free light chains and their association with clinical phenotypes, serology and activity in patients with IgG4-related disease. Sci. Rep. 2021, 11, 1832. [Google Scholar] [CrossRef]
- Tsai, H.C.; Tung, H.Y.; Liu, C.W.; Su, C.F.; Sun, Y.S.; Chen, W.S.; Chen, M.H.; Lai, C.C.; Liao, H.T.; Yang, Y.Y.; et al. Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease-a retrospective investigation of 845 patients and its clinical relevance. Clin. Rheumatol. 2022, 41, 115–122. [Google Scholar] [CrossRef] [PubMed]
- Campochiaro, C.; Ramirez, G.A.; Bozzolo, E.P.; Lanzillotta, M.; Berti, A.; Baldissera, E.; Dagna, L.; Praderio, L.; Scotti, R.; Tresoldi, M.; et al. IgG4-related disease in Italy: Clinical features and outcomes of a large cohort of patients. Scand. J. Rheumatol. 2016, 45, 135–145. [Google Scholar] [CrossRef]
- Wallace, Z.S.; Zhang, Y.; Perugino, C.A.; Naden, R.; Choi, H.K.; Stone, J.H.; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: An analysis of two international cross-sectional cohorts. Ann. Rheum. Dis. 2019, 78, 406–412. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.Y.C.; Mattman, A.; Seidman, M.A.; Carruthers, M.N. IgG4-related disease: What a hematologist needs to know. Haematologica 2019, 104, 444–455. [Google Scholar] [CrossRef]
- Lin, W.; Lu, S.; Chen, H.; Wu, Q.; Fei, Y.; Li, M.; Zhang, X.; Tian, X.; Zheng, W.; Leng, X.; et al. Clinical characteristics of immunoglobulin G4-related disease: A prospective study of 118 Chinese patients. Rheumatology 2015, 54, 1982–1990. [Google Scholar] [CrossRef]
- Della-Torre, E.; Lanzillotta, M.; Doglioni, C. Immunology of IgG4-related disease. Clin. Exp. Immunol. 2015, 181, 191–206. [Google Scholar] [CrossRef] [PubMed]
- Stone, J.R. Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease. Curr. Opin. Rheumatol. 2011, 23, 88–94. [Google Scholar] [CrossRef] [PubMed]
- Prapruttam, D.; Hedgire, S.S.; Mani, S.E.; Chandramohan, A.; Shyamkumar, N.K.; Harisinghani, M. Tuberculosis--the great mimicker. Semin. Ultrasound CT MR 2014, 35, 195–214. [Google Scholar] [CrossRef]
- (PHMPT) Public Health & Medical Professionals for Transparency, Pfizer’s Documents. 2022. Available online: https://phmpt.org/ (accessed on 10 July 2023).
- Pfizer. 5.3.6 Cumulative Analysis of Post-Authorization of Adverse Event Reports of PF-07302048 (BNT162B2) Received through 28-Feb-2021. FDA-CBER-2021-5683-0000054. Public Health and Medical Professionals for Transparency (PHMPT). Available online: https://phmpt.org/pfizer-16-plus-documents/ (accessed on 14 July 2023).
- Nuovo, G.J.; Suster, D.; Sawant, D.; Mishra, A.; Michaille, J.J.; Tili, E. The amplification of CNS damage in Alzheimer’s disease due to SARS-CoV2 infection. Ann. Diagn. Pathol. 2022, 61, 152057. [Google Scholar] [CrossRef]
- Rastogi, A.; Bingeliene, A.; Strafella, A.P.; Tang-Wai, D.F.; Wu, P.E.; Mandell, D.M. Reversible neurological and brain MRI changes following COVID-19 vaccination: A case report. J. Neuroradiol. 2022, 49, 428–430. [Google Scholar] [CrossRef]
- Rhea, E.M.; Logsdon, A.F.; Hansen, K.M.; Williams, L.M.; Reed, M.J.; Baumann, K.K.; Holden, S.J.; Raber, J.; Banks, W.A.; Erickson, M.A. The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Nat. Neurosci. 2021, 24, 368–378. [Google Scholar] [CrossRef]
- Mörz, M. A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against COVID-19. Vaccines 2022, 10, 1651. [Google Scholar] [CrossRef]
- Kim, E.S.; Jeon, M.T.; Kim, K.S.; Lee, S.; Kim, S.; Kim, D.G. Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells. Viruses 2021, 13, 2021. [Google Scholar] [CrossRef] [PubMed]
- Khaddaj-Mallat, R.; Aldib, N.; Bernard, M.; Paquette, A.S.; Ferreira, A.; Lecordier, S.; Saghatelyan, A.; Flamand, L.; ElAli, A. SARS-CoV-2 deregulates the vascular and immune functions of brain pericytes via Spike protein. Neurobiol. Dis. 2021, 161, 105561. [Google Scholar] [CrossRef] [PubMed]
- Fontes-Dantas, F.L.; Fernandes, G.G.; Gutman, E.G.; De Lima, E.V.; Antonio, L.S.; Hammerle, M.B.; Mota-Araujo, H.P.; Colodeti, L.C.; Araújo, S.M.B.; Froz, G.M.; et al. SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice. Cell Rep. 2023, 42, 112189. [Google Scholar] [CrossRef] [PubMed]
- Oh, J.; Cho, W.H.; Barcelon, E.; Kim, K.H.; Hong, J.; Lee, S.J. SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death. Sci. Rep. 2022, 12, 5496. [Google Scholar] [CrossRef] [PubMed]
- Tillman, T.S.; Chen, Q.; Bondarenko, V.; Coleman, J.A.; Xu, Y.; Tang, P. SARS-CoV-2 Spike Protein Downregulates Cell Surface alpha7nAChR through a Helical Motif in the Spike Neck. ACS Chem. Neurosci. 2023, 14, 689–698. [Google Scholar] [CrossRef]
- Rong, Z.; Mai, H.; Kapoor, S.; Puelles, V.G.; Czogalla, J.; Schädler, J.; Vering, J.; Delbridge, C.; Steinke, H.; Frenzel, H.; et al. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19. bioRxiv 2023, preprint. [Google Scholar] [CrossRef]
- Olajide, O.A.; Iwuanyanwu, V.U.; Adegbola, O.D.; Al-Hindawi, A.A. SARS-CoV-2 Spike Glycoprotein S1 Induces Neuroinflammation in BV-2 Microglia. Mol. Neurobiol. 2022, 59, 445–458. [Google Scholar] [CrossRef]
- Wu, Z.; Zhang, X.; Huang, Z.; Ma, K. SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro. Int. J. Mol. Sci. 2022, 23, 3394. [Google Scholar] [CrossRef]
- Winkler, E.S.; Bailey, A.L.; Kafai, N.M.; Sharmila, N.; McCune, B.T.; Jinsheng, Y.; Fox, J.M.; Chen, R.E.; Earnest, J.J.; Keeler, S.P.; et al. SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat. Immunol. 2020, 21, 1327–1335. [Google Scholar] [CrossRef]
- Lykhmus, O.; Kalashnyk, O.; Skok, M. Positive Allosteric Modulation of Alpha7 Nicotinic Acetylcholine Receptors Transiently Improves Memory but Aggravates Inflammation in LPS-Treated Mice. Front. Aging Neurosci. 2020, 11, 359. [Google Scholar] [CrossRef]
- Lykhmus, O.; Kalashnyk, O.; Koval, L.; Krynina, O.; Komisarenko, S.; Skok, M. Immunization with 674–685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice. Biochem. Biophys. Res. Commun. 2022, 622, 57–63. [Google Scholar] [CrossRef]
- Villeda, S.A.; Luo, J.; Mosher, K.I.; Zou, B.; Britschgi, M.; Bieri, G.; Stan, T.M.; Fainberg, N.; Ding, Z.; Eggel, A.; et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 2011, 477, 90–94. [Google Scholar] [CrossRef] [PubMed]
- Fernández-Castañeda, A.; Lu, P.; Geraghty, A.C.; Song, E.; Lee, M.H.; Wood, J.; O’Dea, M.R.; Dutton, S.; Shamardani, K.; Nwangwu, K.; et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell 2022, 185, 2452–2468.e16. [Google Scholar] [CrossRef] [PubMed]
- Shrestha, N.K.; Burke, P.C.; Nowacki, A.S.; Simon, J.F.; Hagen, A.; Gordon, S.M. Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine. Open Forum Infect. Dis. 2023, 10, ofad209. [Google Scholar] [CrossRef] [PubMed]
- Coleman, J.M.; Naik, C.; Holguin, F.; Ray, A.; Ray, P.; Trudeau, J.B.; Wenzel, S.E. Epithelial eotaxin-2 and eotaxin-3 expression: Relation to asthma severity, luminal eosinophilia and age at onset. Thorax 2012, 67, 1061–1066. [Google Scholar] [CrossRef]
- Rojas-Ramos, E.; Avalos, A.F.; Perez-Fernandez, L.; Cuevas-Schacht, F.; Valencia-Maqueda, E.; Teran, L.M. Role of the chemokines RANTES, monocyte chemotactic proteins-3 and −4, and eotaxins-1 and −2 in childhood asthma. Eur. Respir. J. 2003, 22, 310–316. [Google Scholar] [CrossRef]
- Holgate, S.T. Mucosal Immunology; Academic Press: Cambridge, MA, USA, 2015. [Google Scholar] [CrossRef]
- Nyström, S.; Hammarström, P. Amyloidogenesis of SARS-CoV-2 Spike Protein. J. Am. Chem. Soc. 2022, 144, 8945–8950. [Google Scholar] [CrossRef]
- Maatuk, N.; Samson, A.O. Modeling the binding mechanism of Alzheimer’s Aβ1-42 to nicotinic acetylcholine receptors based on similarity with snake α-neurotoxins. Neurotoxicology 2013, 34, 236–242. [Google Scholar] [CrossRef]
- Lasala, M.; Fabiani, C.; Corradi, J.; Antollini, S.; Bouzat, C. Molecular Modulation of Human α7 Nicotinic Receptor by Amyloid-β Peptides. Front. Cell. Neurosci. 2019, 13, 37. [Google Scholar] [CrossRef]
- Dhakal, S.; Wyant, C.E.; George, H.E.; Morgan, S.E.; Rangachari, V. Prion-like C-Terminal Domain of TDP-43 and α-Synuclein Interact Synergistically to Generate Neurotoxic Hybrid Fibrils. J. Mol. Biol. 2021, 433, 166953. [Google Scholar] [CrossRef]
- Tetz, G.; Tetz, V. Prion-like Domains in Spike Protein of SARS-CoV-2 Differ across Its Variants and Enable Changes in Affinity to ACE2. Microorganisms 2022, 10, 280. [Google Scholar] [CrossRef]
- Nonaka, T.; Hasegawa, M. TDP-43 Prions. Cold Spring Harb. Perspect. Med. 2018, 8, a024463. [Google Scholar] [CrossRef]
- Classen, J. COVID-19 RNA based vaccines and the risk of prion disease. Microbiol. Infect. Dis. 2021, 5, 1–3. [Google Scholar] [CrossRef]
- Idrees, D.; Kumar, V. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration. Biochem. Biophys. Res. Commun. 2021, 554, 94–98. [Google Scholar] [CrossRef] [PubMed]
- Kuvandik, A.; Özcan, E.; Serin, S.; Sungurtekin, H. Creutzfeldt-Jakob Disease After the COVID-19 Vaccination. Turk. J. Intensive Care 2021, 20, 61–64. [Google Scholar] [CrossRef]
- Wang, F.; Wang, X.; Yuan, C.G.; Ma, J. Generating a prion with bacterially expressed recombinant prion protein. Science 2010, 327, 1132–1135. [Google Scholar] [CrossRef]
- Young, M.J.; O’Hare, M.; Matiello, M.; Schmahmann, J.D. Creutzfeldt-Jakob disease in a man with COVID-19: SARS-CoV-2-accelerated neurodegeneration? Brain Behav. Immun. 2020, 89, 601–603. [Google Scholar] [CrossRef]
- d’Errico, P.; Meyer-Luehmann, M. Mechanisms of Pathogenic Tau and Abeta Protein Spreading in Alzheimer’s Disease. Front. Aging Neurosci. 2020, 12, 265. [Google Scholar] [CrossRef]
- Duda, J.E.; Lee, V.M.; Trojanowski, J.Q. Neuropathology of synuclein aggregates. J. Neurosci. Res. 2000, 61, 121–127. [Google Scholar] [CrossRef]
- Stefano, G.B. Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID. Med. Sci. Monit. 2021, 27, e931447. [Google Scholar] [CrossRef]
- MedAlerts.org. This is VAERS ID 1754471. National Vaccine Information Center: 2021. Available online: https://medalerts.org/vaersdb/findfield.php (accessed on 4 July 2023).
- MedAlerts.org. This is VAERS ID 1777781. National Vaccine Information Center: 2021. Available online: https://medalerts.org/vaersdb/findfield.php (accessed on 4 July 2023).
- Australian Bureau of Statistics (ABS). Provisional Mortality Statistics: Reference Period: Jan—Dec 2022; abs.gov.au, 2023. Available online: https://www.abs.gov.au/statistics/health/causes-death/provisional-mortality-statistics/jan-dec-2022 (accessed on 7 July 2023).
- Australian Bureau of Statistics (ABS). Provisional Mortality Statistics; Australian Bureau of Statistics (ABS): Canberra, Australia, 2023.
- Kuo, P.H.; Chiang, C.H.; Wang, Y.T.; Doudeva, L.G.; Yuan, H.S. The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids. Nucleic Acids Res. 2014, 42, 4712–4722. [Google Scholar] [CrossRef]
- King, O.D.; Gitler, A.D.; Shorter, J. The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 2012, 1462, 61–80. [Google Scholar] [CrossRef] [PubMed]
- Tavassoly, O.; Safavi, F.; Tavassoly, I. Seeding Brain Protein Aggregation by SARS-CoV-2 as a Possible Long-Term Complication of COVID-19 Infection. ACS Chem. Neurosci. 2020, 11, 3704–3706. [Google Scholar] [CrossRef] [PubMed]
- Mueller, B.K.; Subramaniam, S.; Senes, A. A frequent, GxxxG-mediated, transmembrane association motif is optimized for the formation of interhelical Calpha-H hydrogen bonds. Proc. Natl. Acad. Sci. USA 2014, 111, E888–E895. [Google Scholar] [CrossRef] [PubMed]
- Prusiner, S.B. Novel proteinaceous infectious particles cause scrapie. Science 1982, 216, 136–144. [Google Scholar] [CrossRef]
- Decock, M.; Stanga, S.; Octave, J.N.; Dewachter, I.; Smith, S.O.; Constantinescu, S.N.; Kienlen-Campard, P. Glycines from the APP GXXXG/GXXXA Transmembrane Motifs Promote Formation of Pathogenic Abeta Oligomers in Cells. Front. Aging Neurosci. 2016, 8, 107. [Google Scholar] [CrossRef] [PubMed]
- Seneff, S.; Nigh, G. Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19. Int. J. Vaccine Theory Pract. Res. 2021, 2, 38–79. [Google Scholar] [CrossRef]
- Liu-Yesucevitz, L.; Bilgutay, A.; Zhang, Y.J.; Vanderweyde, T.; Citro, A.; Mehta, T.; Zaarur, N.; McKee, A.; Bowser, R.; Sherman, M.; et al. Tar DNA binding protein-43 (TDP-43) associates with stress granules: Analysis of cultured cells and pathological brain tissue. PLoS ONE 2010, 5, e13250. [Google Scholar] [CrossRef]
- Bosco, D.A.; Lemay, N.; Ko, H.K.; Zhou, H.; Burke, C.; Kwiatkowski, T.J., Jr.; Sapp, P.; McKenna-Yasek, D.; Brown, R.H., Jr.; Hayward, L.J. Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules. Hum. Mol. Genet. 2010, 19, 4160–4175. [Google Scholar] [CrossRef]
- Cox, P.A.; Richer, R.; Metcalf, J.S.; Banack, S.A.; Codd, G.A.; Bradley, W.G. Cyanobacteria and BMAA exposure from desert dust: A possible link to sporadic ALS among Gulf War veterans. Amyotroph. Lateral Scler. 2009, 10 (Suppl S2), 109–117. [Google Scholar] [CrossRef]
- Stefano, G.B.; Buttiker, P.; Weissenberger, S.; Anders, M.; Raboch, J.; Ptacek, R.; Kream, R.M. Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior. Cell. Mol. Neurobiol. 2023, 43, 2621–2626. [Google Scholar] [CrossRef]
- Donaldson, D.S.; Bradford, B.M.; Else, K.J.; Mabbott, N.A. Accelerated onset of CNS prion disease in mice co-infected with a gastrointestinal helminth pathogen during the preclinical phase. Sci. Rep. 2020, 10, 4554. [Google Scholar] [CrossRef] [PubMed]
- Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Munch, A.E.; Chung, W.S.; Peterson, T.C.; et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017, 541, 481–487. [Google Scholar] [CrossRef] [PubMed]
- Makarava, N.; Chang, J.C.; Molesworth, K.; Baskakov, I.V. Region-specific glial homeostatic signature in prion diseases is replaced by a uniform neuroinflammation signature, common for brain regions and prion strains with different cell tropism. Neurobiol. Dis. 2020, 137, 104783. [Google Scholar] [CrossRef]
- Xu, J.; Wei, H.; You, P.; Sui, J.; Xiu, J.; Zhu, W.; Xu, Q. Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice. Front. Mol. Neurosci. 2023, 16, 1177961. [Google Scholar] [CrossRef]
- Kyriakopoulos, A.M.; Nigh, G.; McCullough, P.A.; Seneff, S. Mitogen Activated Protein Kinase (MAPK) Activation, p53, and Autophagy Inhibition Characterize the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein Induced Neurotoxicity. Cureus 2022, 14, e32361. [Google Scholar] [CrossRef]
- Thomas, C.A.; Paquola, A.C.M.; Muotri, A.R. LINE-1 retrotransposition in the nervous system. Annu. Rev. Cell Dev. Biol. 2012, 28, 555–573. [Google Scholar] [CrossRef]
- Terry, D.M.; Devine, S.E. Aberrantly High Levels of Somatic LINE-1 Expression and Retrotransposition in Human Neurological Disorders. Front. Genet. 2020, 10, 1244. [Google Scholar] [CrossRef]
- Shamila, D.; Alipoor, S.D.; Moratz, E.; Garssen, J.; Movassaghi, M.; Mirsaeidi, M.; Adcock, I.M. Exosomes and Exosomal miRNA in Respiratory Diseases. Mediat. Inflamm. 2016, 2016, 5628404. [Google Scholar] [CrossRef]
- Visacri, M.B.; Nicoletti, A.S.; Pincinato, E.C.; Loren, P.; Saavedra, N.; Saavedra, K.; Salazar, L.A.; Moriel, P. Role of miRNAs as biomarkers of COVID-19: A scoping review of the status and future directions for research in this field. Biomark. Med. 2021, 15, 1785–1795. [Google Scholar] [CrossRef] [PubMed]
- Pogue, A.I.; Lukiw, W.J. microRNA-146a-5p, Neurotropic Viral Infection and Prion Disease (PrD). Int. J. Mol. Sci. 2021, 22, 9198. [Google Scholar] [CrossRef]
- Lukiw, W.J.; Dua, P.; Pogue, A.I.; Eicken, C.; Hill, J.M. Upregulation of micro RNA-146a (miRNA-146a), a marker for inflammatory neurodegeneration, in sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Straussler-Scheinker (GSS) syndrome. J. Toxicol. Environ. Health A 2011, 74, 1460–1468. [Google Scholar] [CrossRef] [PubMed]
- Norrby, E. Prions and protein-folding diseases. J. Intern. Med. 2011, 270, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Horwich, A.L.; Weissman, J.S. Deadly conformations—Protein misfolding in prion disease. Cell 1997, 89, 499–510. [Google Scholar] [CrossRef] [PubMed]
- Tripathi, U.; Nchioua, R.; Prata, L.G.P.L.; Zhu, Y.; Gerdes, E.O.W.; Giorgadze, N.; Pirtskhalava, T.; Parker, E.; Xue, A.; Espindola-Netto, J.M.; et al. SARS-CoV-2 causes senescence in human cells and exacerbates the senescence-associated secretory phenotype through TLR-3. Aging 2021, 13, 21838–21854. [Google Scholar] [CrossRef]
- Sfera, A.; Thomas, K.; Sfera, D.; Anton, J.; Andronescu, C.; Jafri, N.; Susanna, S.; Kozlakidis, Z. Do messenger RNA vaccines induce pathological syncytial? Int. J. Pathol. Clin. Res. 2022, 8, 137. [Google Scholar]
- Huang, L.; Jin, R.; Li, J.; Luo, K.; Huang, T.; Wu, D.; Wang, W.; Chen, R.; Xiao, G. Macromolecular crowding converts the human recombinant PrPC to the soluble neurotoxic beta-oligomers. FASEB J. 2010, 24, 3536–3543. [Google Scholar] [CrossRef]
- Dalgleish, A. Interview with Professor Angus Dalgleish. Immunotherapy 2016, 8, 1271–1276. [Google Scholar] [CrossRef]
- Dalgleish, A. As an Oncologist I am Seeing People with Stable Cancer Rapidly Progress after Being Forced to Have a Booster. Letter to Dr Abbassi, Editor-in-Chief BMJ. dailysceptic.org. 2022. Available online: https://dailysceptic.org/2022/11/26/as-an-oncologist-i-am-seeing-people-with-stable-cancer-rapidly-progress-after-being-forced-to-have-a-booster/ (accessed on 11 June 2023).
- Pio, R.; Ajona, D.; Ortiz-Espinosa, S.; Mantovani, A.; Lambris, J.D. Complementing the cancer-immunity cycle. Front. Immunol. 2019, 10, 774. [Google Scholar] [CrossRef]
- Alsaab, H.O.; Sau, S.; Alzhrani, R.; Tatiparti, K.; Bhise, K.; Kashaw, S.K.; Lyer, A.K. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome. Front. Pharmacol. 2017, 8, 561. [Google Scholar] [CrossRef]
- Bishawi, M.; Bowles, D.; Pla, M.M.; Oakes, F.; Chiang, Y.S.; Schroder, J.; Milano, C.; Glass, C. PD-1 and PD-L1 expression in cardiac transplantation. Cardiovasc. Pathol. 2021, 54, 107331. [Google Scholar] [CrossRef]
- Loacker, L.; Kimpel, J.; Bánki, Z.; Schmidt, C.Q.; Griesmacher, A.; Anliker, M. Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with SARS-CoV2 mRNA or vector vaccine. Clin. Chem. Lab. Med. 2022, 61, e17–e19. [Google Scholar] [CrossRef] [PubMed]
- Diskin, C.; Ryan, T.A.J.; O’Neill, L.J. Modification of Proteins by Metabolites in Immunity. Immunity 2021, 54, 19–31. [Google Scholar] [CrossRef]
- Mishra, R.; Banerjea, A.C. SARS-CoV-2 Spike targets USP33-IRF9 axis via exosomal miR-148a to activate human microglia. Front. Immunol. 2021, 12, 656700. [Google Scholar] [CrossRef] [PubMed]
- Seneff, S.; Nigh, G.; Kyriakopoulos, A.M.; McCoulough, P.A. Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs. Food Chem. Toxicol. 2022, 164, 113008. [Google Scholar] [CrossRef]
- Hofer, M.J.; Li, W.; Lim, S.L.; Campbell, I.L. The type I interferon-alpha mediates a more severe neurological disease in the absence of the canonical signaling molecule interferon regulatory factor 9. J. Neurosci. 2010, 30, 1149–1157. [Google Scholar] [CrossRef] [PubMed]
- Rasmussen, S.A.; Abul-Husn, N.S.; Casanova, J.L.; Daly, M.J.; Rehm, H.L.; Murray, M.F. The intersection of genetics and COVID-19 in 2021: Preview of the 2021 Rodney Howell Symposium. Genet. Med. 2021, 23, 1001–1003. [Google Scholar] [CrossRef]
- Liu, J.; Wang, J.; Xu, J.; Xia, H.; Wang, Y.; Zhang, C.; Chen, W.; Zhang, H.; Liu, Q.; Zhu, R.; et al. Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines. Cell Discov. 2021, 7, 99. [Google Scholar] [CrossRef]
- Li, S.; Silvestri, V.; Leslie, G.; Rebbeck, T.R.; Neuhausen, S.L.; Hopper, J.L.; Nielsen, H.R.; Lee, A.; Yang, X.; McGuffog, L.; et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. J. Clin. Oncol. 2022, 40, 1529–1541. [Google Scholar] [CrossRef]
- Nuovo, G.J.; Magro, C.; Shaffer, T.; Awad, H.; Suster, D.; Mikhail, S.; He, B.; Michaille, J.J.; Liechty, B.; Tili, E. Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein. Ann. Diagn. Pathol. 2021, 51, 151682. [Google Scholar] [CrossRef]
- Mezache, L.; Nuovo, G.J.; Suster, D.; Tili, E.; Awad, H.; Radwański, P.B.; Veeraraghavan, R. Histologic, viral, and molecular correlates of heart disease in fatal COVID-19. Ann. Diagn. Pathol. 2022, 60, 151983. [Google Scholar] [CrossRef]
- Choi, J. Fauci: Amount of Virus in ‘Breakthrough Delta Cases Almost Identical’ to Unvaccinated. The Hill: Thehill.com. 2021. Available online: https://thehill.com/homenews/sunday-talk-shows/565831-fauci-amount-of-virus-in-breakthrough-delta-cases-almost-identical/ (accessed on 7 April 2023).
- Schwab, C.; Domke, L.M.; Hartmann, L.; Stenzinger, A.; Longerich, T.; Schirmacher, P. Autopsy-based histopathological characterization of myocarditis after anti-SARS-CoV-2-vaccination. Clin. Res. Cardiol. 2023, 112, 431–440. [Google Scholar] [CrossRef] [PubMed]
- Burkhardt, A. Reutlingen Autopsy/Histology Study: Side-Effects from Corona Vaccinations. PowerPoint Conference Presentation (in German). Corona-blog.net. 2022. Available online: https://corona-blog.net/2022/03/10/reutlinger-autopsie-histologie-studie-nebenwirkungen-und-todesfaelle-durch-die-corona-impfungen/ (accessed on 7 April 2023).
- Burkhardt, A. Pathology Conference: Vaccine-Induced Spike Protein Production in the Brain, Organs etc., now Proven. Report24.news. 2022. Available online: https://report24.news/pathologie-konferenz-impfinduzierte-spike-produktion-in-gehirn-u-a-organen-nun-erwiesen/ (accessed on 7 April 2023).
- Domazet-Lošo, T. mRNA Vaccines: Why Is the Biology of Retroposition Ignored? Genes 2022, 13, 719. [Google Scholar] [CrossRef] [PubMed]
- Dopp, K.; Seneff, S. COVID-19 and all-cause mortality data by age group reveals risk of COVID vaccine-induced fatality is equal to or greater than the risk of a COVID death for all age groups under 80 years old as of 6 February 2022. Vixra.org 2022, 21, preprint. [Google Scholar]
- Bajaj, V.; Gadi, N.; Spihlman, A.P.; Wu, S.C.; Choi, C.H.; Moulton, V.R. Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections? Front. Physiol. 2020, 11, 571416. [Google Scholar] [CrossRef]
- Chen, Y.; Li, C.; Liu, F.; Ye, Z.; Song, W.; Lee, A.C.Y.; Shuai, H.; Lu, L.; To, K.K.; Chan, J.F.; et al. Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model. Emerg. Microbes Infect. 2022, 11, 368–383. [Google Scholar] [CrossRef]
- Vo, A.D.; La, J.; Wu, J.T.; Strymish, J.M.; Ronan, M.; Brophy, M.; Do, N.V.; Branch-Elliman, W.; Fillmore, N.R.; Monach, P.A. Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals. JAMA Netw. Open 2022, 5, e2240037. [Google Scholar] [CrossRef]
Author | Constituents/Tissue Type/Assay Technique | Duration Measured |
---|---|---|
Animal | ||
Pfizer (Japanese MoH) 2020 [46] | Radiolabelled LNP in plasma and tissues | 140 h–14 days |
Human | ||
Ogata et al. (2021) [52] | Spike protein and S1 subunit (assay) | 3 days |
Bansal et al. (2021) [57] | Spike Protein | 4 months |
Fertig et al. (2022) [50] | LNPs and mRNA | 15 days |
Röltgen et al. (2022) [53] | mRNA and Spike Protein in ipsilateral lymph nodes; 2–7 days post dose in blood | 60 days |
Yamamoto et al. (2022) [58] | Spike Protein in skin | 3 months |
Yonker et al. (2023) [54] | Spike Protein in blood | 1–19 days in cases of myocarditis |
Castruita et al. (2023) [51] | mRNA in plasma | 28 days |
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Parry, P.I.; Lefringhausen, A.; Turni, C.; Neil, C.J.; Cosford, R.; Hudson, N.J.; Gillespie, J. ‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA. Biomedicines 2023, 11, 2287. https://doi.org/10.3390/biomedicines11082287
Parry PI, Lefringhausen A, Turni C, Neil CJ, Cosford R, Hudson NJ, Gillespie J. ‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA. Biomedicines. 2023; 11(8):2287. https://doi.org/10.3390/biomedicines11082287
Chicago/Turabian StyleParry, Peter I., Astrid Lefringhausen, Conny Turni, Christopher J. Neil, Robyn Cosford, Nicholas J. Hudson, and Julian Gillespie. 2023. "‘Spikeopathy’: COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA" Biomedicines 11, no. 8: 2287. https://doi.org/10.3390/biomedicines11082287