Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis
Open accessAbstract
Vaccination is a major tool for mitigating the coronavirus disease 2019 (COVID-19) pandemic, and mRNA vaccines are central to the ongoing vaccination campaign that is undoubtedly saving thousands of lives. However, adverse effects (AEs) following vaccination have been noted which may relate to a proinflammatory action of the lipid nanoparticles used or the delivered mRNA (i.e., the vaccine formulation), as well as to the unique nature, expression pattern, binding profile, and proinflammatory effects of the produced antigens - spike (S) protein and/or its subunits/peptide fragments - in human tissues or organs. Current knowledge on this topic originates mostly from cell-based assays or from model organisms; further research on the cellular/molecular basis of the mRNA vaccine-induced AEs will therefore promise safety, maintain trust, and direct health policies.
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saRNA can address shortcomings of mRNA by decreasing the number of doses and administration frequency, mitigating side effects and bolstering manufacturing capacity.
“saRNA can address the shortcomings of mRNA by decreasing the number of doses and the administration frequency, which will mitigate side effects8–10 and bolster manufacturing capacity”
From Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency (2025) · cites this paper as [8]
The section “Anti-SARS-CoV-2 mRNA vaccines and their reported adverse effects” (page not provided) says frequent boosters may increase adverse-effect frequency or severity. That supports a possible benefit from fewer administrations, but it does not establish that saRNA reduces dosing or that fewer doses will mitigate side effects. (LLM, conf=0.86)
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References 143 · Cited by 273
Research works printed but not linked: 4
- [21]European Medicines Agency Comirnaty Assessment Report COVID-19 Vaccine Comirnaty. EMA/707383/2020 Corr.1*1 2021 European Medicines Agency
- [22]European Medicines Agency Moderna Assessment Report COVID-19 Vaccine Moderna. EMA/15689/2021 Corr.1*1 2021 European Medicines Agency
- [38]Hoeg T. SARS-CoV-2 mRNA vaccination-associated myocarditis in children ages 12–17: a stratified national database analysis medRxiv 2021 Published online September 8, 2021 10.1101/2021.08.30.21262866 · DOI
- [59]Visvabharathy L. Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination medRxiv 2021 Published online October 29, 2021 10.1101/2021.08.08.21261763 · DOI
- Authors
- Trougakos, I. P., Terpos, E., Alexopoulos, H., Politou, M., Paraskevis, D., Scorilas, A., Kastritis, E., Andreakos, E., & Dimopoulos, M. A.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Biomedical Research Foundation of the Academy of Athens (GR)
- Corresponding author
- Trougakos, Ioannis P.
- ORCID
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 28
- Issue
- 7
- Pages
- 542-554
- ISSN
- 1471-4914 (ISSN-L)
- PMC
- PMC9021367
- OpenAlex
- W4224212891
- Cited by
- 273
- References
- 143
- Citations by year
- 2026: 29 · 2025: 65 · 2024: 69 · 2023: 83 · 2022: 27
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- COVID-19 mRNA vaccine, vaccine adverse events, spike protein, lipid nanoparticles, pro-inflammatory effects, vaccine safety, SARS-CoV-2, vaccine immunogenicity
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Antibodies, Viral, Humans, Liposomes, RNA, Messenger, Vaccines, Synthetic, Viral Vaccines, Nanoparticles, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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