John Murphy, The COVID 19 Long-haul Foundation

Abstract

The rapid deployment of mRNA vaccines against SARS-CoV-2 marked a historic milestone in biotechnology. While these vaccines have demonstrated minor efficacy in preventing severe COVID-19, emerging data from post-marketing surveillance and independent studies have raised concerns about serious adverse events. This article synthesizes findings from over ten peer-reviewed sources to examine the biological behavior of mRNA vaccines, including biodistribution, complications, and genomic implications. We explore the etiology of vaccine-related injuries, the migration of mRNA beyond the injection site, and whether vaccine components persist in the body.

Introduction

mRNA vaccines—specifically BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—were authorized under emergency use in late 2020. These vaccines deliver synthetic mRNA encoding the SARS-CoV-2 spike protein via lipid nanoparticles (LNPs), prompting host cells to produce antigen and elicit an immune response. While the technology is novel and effective, its long-term safety profile remains under scrutiny. Recently, the vaccines have been removed from Emergency Use Authorization because they have not been fully tested under FDA clinical trials requirements and appear to lack effectiveness and perhaps safety, especially in the longer-term. No one knows what consequences (Positive or Negative) these therapies will have over time. Testing needs to be expedited to protect the population.

Reported Complications and Adverse Events

A systematic review by Xu et al. (2023) analyzed over 5 million subjects and found that adverse events (AEs) occurred in 62–70% of recipients, with systemic AEs (e.g., fever, fatigue, myalgia) in up to 48%. Most were mild, but serious events have been documented:

• Myocarditis and Pericarditis: Particularly in young males, with incidence rates ranging from 1 in 5,000 to 1 in 20,000 depending on age and dose2.
• Thrombosis with Thrombocytopenia Syndrome (TTS): More common with adenoviral vaccines, but rare cases have been reported with mRNA platforms.
• Neurological Events: Guillain-Barré syndrome, Bell’s palsy, and small fiber neuropathy have been observed post-vaccination.
• Anaphylaxis: Occurs in approximately 2–5 cases per million doses, often linked to polyethylene glycol (PEG) in LNPs.
• Deaths: While causality is difficult to establish, VAERS and EudraVigilance databases have recorded deaths temporally associated with vaccination. Most occurred in elderly or high-risk individuals1.

Etiology of Vaccine-Related Injury

The mechanisms behind these complications are multifactorial:

• Immune Overactivation: mRNA vaccines can trigger robust innate immune responses, including type I interferon signaling, which may exacerbate autoimmune tendencies.
• Molecular Mimicry: The spike protein shares homology with human proteins, potentially leading to cross-reactive autoantibodies.
• Lipid Nanoparticle Toxicity: LNPs may induce inflammation and cytotoxicity, particularly in hepatic and splenic tissues.
• Spike Protein Pathogenicity: Circulating spike protein has been detected post-vaccination and may bind ACE2 receptors, contributing to endothelial dysfunction.

Biodistribution and mRNA Migration

Contrary to early claims that mRNA remains localized at the injection site, animal studies and autopsy data suggest systemic distribution:

• Pfizer’s own biodistribution study in rodents showed LNPs accumulating in the liver, spleen, ovaries, and adrenal glands.
• Bahl et al. (2022) demonstrated spike protein expression in distant tissues, including the heart and brain, in murine models.
• Röltgen et al. (2022) found vaccine mRNA and spike protein in lymph nodes up to 60 days post-injection.

This systemic migration raises concerns about off-target effects, especially in sensitive tissues like myocardium and endothelium.

Concerns about off-target effects of mRNA vaccines center on the possibility that the synthetic messenger RNA—designed to instruct cells to produce the SARS-CoV-2 spike protein—may behave unpredictably once inside the body. While the intended mechanism is localized antigen production at the injection site, studies have shown that lipid nanoparticles (LNPs) used to deliver mRNA can migrate systemically. Biodistribution data from Pfizer’s own preclinical studies revealed accumulation in organs such as the liver, spleen, ovaries, and adrenal glands. This raises questions about unintended protein expression in sensitive tissues, which could provoke immune responses or cellular stress in non-target areas.

In the short term, off-target effects may manifest as systemic inflammation, fever, fatigue, or more serious complications like myocarditis, particularly in younger males. These reactions are thought to stem from immune overactivation or spike protein interaction with ACE2 receptors in vascular and cardiac tissues. The Penn Medicine Center for Evidence-based Practice reported that severe systemic adverse events occurred in 5–10% of trial participants, with higher rates following the second dose. While most symptoms resolve within days, some individuals experience lingering effects, including neurological symptoms and autoimmune flares.

Long-term consequences are more speculative but increasingly studied. One concern is the persistence of spike protein or mRNA in lymphoid tissues weeks after vaccination, as shown by Röltgen et al. (2022), which may contribute to chronic immune stimulation. Another is the theoretical risk of reverse transcription—where vaccine mRNA is converted into DNA and potentially integrated into the host genome. Aldén et al. (2022) demonstrated that this process can occur in vitro in human liver cells via LINE-1 elements, though in vivo relevance remains unproven. If integration were to occur in germline cells, it could have transgenerational implications, although no clinical evidence currently supports this scenario to date.

The danger of these consequences depends on individual susceptibility, dose, and immune status. For most people, mRNA vaccines are well tolerated and effective. However, for a minority, off-target effects may lead to serious complications. These include myocarditis, small fiber neuropathy, autoimmune disease activation, and vascular injury. Stephanie Seneff and Greg Nigh’s review highlights the potential for prion-like domains in the spike protein to contribute to neurodegenerative processes, though this remains a controversial hypothesis requiring further validation.

Ultimately, the safety profile of mRNA vaccines is still evolving. While they represent a powerful tool in pandemic control, their novel biology demands ongoing scrutiny. Longitudinal studies, improved pharmacovigilance, and transparent data sharing will be essential to fully understand the scope and scale of off-target risks over time.

Genomic Considerations: Does mRNA Integrate or Persist?

mRNA vaccines do not contain reverse transcriptase and are not designed to integrate into host DNA. However, recent studies have explored theoretical risks:

• Aldén et al. (2022) reported that spike mRNA from BNT162b2 could be reverse-transcribed in vitro in human liver cells via LINE-1 elements. While integration was not confirmed, the finding warrants further investigation.
• Persistence: mRNA is typically degraded within hours to days, but spike protein and immune activation may persist longer. Röltgen et al. found spike protein in lymphoid tissue weeks after vaccination.

No definitive evidence supports widespread genomic integration, but the possibility of long-term epigenetic or transcriptional changes remains under study.

The advent of mRNA vaccine technology marked a turning point in pandemic response, offering rapid development, scalable production, and high efficacy against SARS-CoV-2. Yet as the global vaccination campaign matured, so did the scrutiny of its biological behavior—particularly the fate of synthetic mRNA once inside the human body. While initial regulatory narratives emphasized localized action at the injection site, emerging data from preclinical studies and molecular biology research suggest that mRNA and its lipid nanoparticle (LNP) delivery system may migrate systemically, raising questions about off-target effects and long-term consequences.

One of the most provocative findings came from an in vitro study by Aldén et al. (2022), which demonstrated that mRNA from the Pfizer-BioNTech vaccine could be reverse-transcribed into DNA in human liver-derived Huh7 cells. This process appeared to be mediated by endogenous LINE-1 elements—retrotransposons capable of encoding reverse transcriptase and endonuclease activity. While the study did not confirm genomic integration, it introduced a new layer of complexity to the safety profile of mRNA vaccines: the possibility that synthetic mRNA might be converted into DNA within human cells.

If such reverse transcription were to occur in vivo, the biological implications would depend on several factors. First, the presence and activity of LINE-1 elements vary across tissues and individuals. In healthy adult somatic cells, LINE-1 is typically suppressed, but it can be reactivated under stress, inflammation, or in certain disease states. Second, for reverse-transcribed DNA to exert lasting effects, it must enter the nucleus and integrate into the host genome—a process that is rare and tightly regulated. Third, the location of integration matters profoundly. Insertion into a noncoding region may be biologically inert, while disruption of a tumor suppressor gene or activation of an oncogene could, in theory, initiate clonal expansion or malignancy.

The short-term consequences of mRNA migration and potential reverse transcription are likely minimal for most individuals. Transient immune activation, mild systemic inflammation, and localized reactogenicity are well-documented and generally self-limiting. However, in rare cases, off-target effects may contribute to more serious outcomes—such as myocarditis, small fiber neuropathy, or autoimmune flares—particularly if spike protein is expressed in sensitive tissues like the myocardium or endothelium. These effects are thought to arise from immune overactivation, molecular mimicry, or spike protein interaction with ACE2 receptors.

The long-term risks, while speculative, warrant careful consideration. Persistent expression of spike protein in non-target tissues could theoretically sustain chronic inflammation or immune dysregulation. If reverse-transcribed DNA were to integrate into the genome, it might lead to insertional mutagenesis, epigenetic drift, or aberrant gene expression. Such events are exceedingly rare, but not unprecedented; retroviral gene therapies have encountered similar challenges in the past. Moreover, if integration occurred in germline cells—an unlikely but biologically possible scenario—it could have transgenerational implications.

It is important to contextualize these risks. The probability of reverse transcription and integration in vivo is unknown, and no epidemiological signal has yet emerged to suggest widespread genomic disruption from mRNA vaccines. Nonetheless, the theoretical possibility underscores the need for ongoing surveillance, transparent data sharing, and rigorous molecular studies. Tissue biopsies, genomic assays, and long-term cohort tracking will be essential to determine whether any integration events occur, and if so, whether they are biologically consequential.

In conclusion, while mRNA vaccines have proven to be a powerful tool in controlling COVID-19, their novel biology demands continued scrutiny. The migration of mRNA beyond the injection site, its potential for reverse transcription via LINE-1 elements, and the hypothetical risks of genomic integration represent areas of active investigation. For most recipients, the benefits of vaccination far outweigh the risks. But for science and public health to maintain credibility, even rare or theoretical concerns must be explored with rigor, transparency, and humility.

Long-Term Prognosis and Surveillance

Most vaccine recipients recover fully from transient side effects. However, individuals with myocarditis, autoimmune flares, or neurological complications may experience prolonged recovery or chronic symptoms. Long-term surveillance is ongoing:

• JAMA Network Open (2025) published a cohort study tracking 29 serious adverse events post-JN.1 booster, noting elevated risks for myocarditis, arrhythmias, and neurological sequelae in the first 28 days post-vaccination.
• Oxford Academic (2024) emphasized the need for expanded data collection in underrepresented populations, including those with prior autoimmune disease.

Conclusion

mRNA COVID-19 vaccines have played a pivotal role in pandemic control, but their safety profile is complex. While most adverse events are mild and transient, rare but serious complications—including myocarditis, neurological injury, and systemic inflammation—have been documented. Biodistribution studies challenge early assumptions of localization, and emerging genomic data suggest the need for continued vigilance. Transparent research, robust pharmacovigilance, and individualized risk-benefit assessments are essential as mRNA platforms expand into other therapeutic domains.

References

1. Andersson NW et al. (2025). Safety of JN.1-Updated mRNA COVID-19 Vaccines. JAMA Network Open, 8(7):e2523557. Study overview
2. Xu W et al. (2023). Real-World Safety of COVID-19 mRNA Vaccines: A Systematic Review. Vaccines, 11(6):1118. Meta-analysis
3. Wong BKF et al. (2024). mRNA Vaccine Effectiveness and Safety. Immunotherapy Advances, 4(1):ltae011. Oxford Academic
4. Vojdani A et al. (2021). Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins with Tissue Antigens. Frontiers in Immunology, 12:705872.
5. EMA Assessment Report. (2020). Comirnaty (Pfizer-BioNTech) Biodistribution Study.
6. Bahl K et al. (2022). Preclinical Evaluation of mRNA Vaccines. Nature Reviews Drug Discovery, 21(3):165–183.
7. Röltgen K et al. (2022). Immune imprinting and persistence of vaccine mRNA. Cell, 185(3):603–613.e14.
8. Aldén M et al. (2022). Intracellular Reverse Transcription of BNT162b2 mRNA. Current Issues in Molecular Biology, 44(3):1115–1126.
9. Mevorach D et al. (2021). Myocarditis after BNT162b2 Vaccination. NEJM, 385(23):2140–2149.
10. Klein NP et al. (2021). Surveillance for Adverse Events After COVID-19 Vaccination. JAMA, 326(14):1390–1399.