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Introduction
A small but provocative study published in the Journal of Clinical Neuroscience has reported something that, until now, had not been documented in the medical literature: the presence of SARS-CoV-2 spike protein inside the walls of cerebral arteries in patients who suffered hemorrhagic strokes—in some cases more than a year after their last mRNA vaccination.
The findings raise uncomfortable questions about how long vaccine-produced proteins persist in the body, where they travel, and whether they could play a role in rare but serious neurological events.
The Background: A New Vaccine Technology
The mRNA vaccines from Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) were the first mRNA vaccines ever deployed at scale in human history. Unlike traditional vaccines—which introduce a weakened or inactivated pathogen, or a piece of its protein, to train the immune system—mRNA vaccines instruct the body’s own cells to temporarily manufacture the spike protein.
That technology was novel. Before 2020, no mRNA vaccine had been approved for human use. As the authors of this study note, this means there was “limited experience” with the platform, and its long-term behavior in the body remained, and remains, incompletely understood.
What the Researchers Set Out to Do
The investigation began with a single, puzzling case. A patient with no history of COVID-19 infection developed an atypical cerebral hemorrhage several months after vaccination. When surgeons removed tissue during surgery, immunohistochemical staining revealed SARS-CoV-2 spike protein in the wall of a blood vessel.
That observation prompted the team—based at Sapporo Teishinkai Hospital and collaborating institutions in Japan—to collect and analyze tissue from hemorrhagic stroke cases between March 2023 and April 2024.
How the Study Was Conducted
Nineteen cases were included. Ten were intracerebral hemorrhages, six were subarachnoid hemorrhages, two involved arteriovenous malformations, and one involved a cavernous malformation.
- The average patient age was about 59 years.
- Fourteen of the nineteen patients (74%) were female.
- Sixteen had received mRNA vaccines; three had not.
- Among the vaccinated, the median number of doses was four.
- The average time from last vaccination to surgery was roughly eleven months.
Tissue samples were examined using immunohistochemical staining for both the spike and nucleocapsid proteins—a key distinction, since the nucleocapsid protein appears only after actual viral infection, not after vaccination.
In three cases, the researchers also used a technique called in situ hybridization, which detects specific RNA sequences, to determine whether the spike protein came from the vaccine or a natural infection.
What They Found
The results were striking.
Spike protein was detected in 43.8% of vaccinated patients—seven of sixteen—and it was found predominantly in the intima, the innermost lining of cerebral arteries. In some cases, the protein was still detectable 17 months after vaccination.
None of the cases showed nucleocapsid protein, which the authors say supports the absence of active viral infection.
In three cases examined with in situ hybridization, the researchers reported finding both vaccine-derived mRNA and viral RNA in the artery walls.
An Unexpected Pattern: Only Women
Perhaps the most puzzling finding concerned sex. Among the 18 cases with usable specimens, all 9 patients with positive spike protein staining were female. No male patient tested positive for spike protein.
The statistical analysis produced a P-value of 0.015, indicating the association was unlikely to be due to chance.
The authors suggest this may point to sex-based differences in how the immune system responds to the vaccine, noting that women are known to mount stronger immune responses to vaccines and infections generally.
Earlier research has shown that women report more persistent symptoms after COVID-19 and are more likely to experience certain post-vaccination conditions.
Signs of Inflammation
Although the researchers found no evidence of active vasculitis—an aggressive inflammatory condition of blood vessels—they did observe something notable in the spike-positive vessels.
In those vessels, they found infiltration of:
- CD4-positive T cells into the intima
- CD68-positive cells into the intima
- CD8-positive cells into the adventitia
These findings were absent in spike-negative cases. The authors interpret this as a possible sign that the presence of spike protein is provoking an immune response in the vessel wall—a hypothesis they describe as speculative, since the samples were taken from tissue surrounding the hemorrhage rather than from the hemorrhage itself.
The Vaccine mRNA Detection: What It Means
The in situ hybridization results deserve particular attention. In cases 4, 5, and 15—patients whose last vaccination had been 17, 12, and 11 months earlier, respectively—the researchers detected both vaccine mRNA and SARS-CoV-2 viral RNA in the arterial intima.
The authors are careful here. They acknowledge that the nucleocapsid protein was consistently negative, which suggests no active infection. But they also note that their method is sensitive and could potentially detect trace amounts of mRNA from unrecognized, asymptomatic infections. They therefore caution against interpreting the spike protein as exclusively vaccine-derived.
Still, the finding that vaccine-encoded mRNA was detectable in arterial tissue many months after injection challenges assumptions about how quickly vaccine material is cleared from the body.
Why This Matters: The Lipid Nanoparticle Question
The study raises a broader issue about lipid nanoparticles—the fatty bubbles that encapsulate mRNA and deliver it into cells.
The authors note that lipid nanoparticles can cross physiological barriers, including the blood-brain barrier and the placental barrier. Where exactly these particles distribute in the body and how long their mRNA cargo remains active are not well characterized.
Earlier research cited in the paper found vaccine-associated mRNA in blood up to 15 days post-vaccination, and another study detected it up to 28 days. This new paper suggests the timeline could be considerably longer—in some cases, over a year.
The authors write that “the actual behavior of mRNA vaccines within the human body may differ from what was previously believed.”
Context: What We Know About Stroke and COVID-19
The paper is careful to acknowledge that SARS-CoV-2 infection itself is linked to stroke risk. The virus can disrupt the blood-brain barrier, dysregulate blood pressure through ACE2 receptors, and trigger coagulopathy—all of which can contribute to both ischemic and hemorrhagic strokes.
The researchers also reference a large Hong Kong epidemiological study that found an increased risk of hemorrhagic stroke in the weeks following BNT162b2 vaccination, but which concluded that the overall risk was lower among vaccinated individuals than among those who had been infected with the virus.
The authors do not dispute that vaccines reduce the risk of severe COVID-19 outcomes. Their concern is narrower and more specific: whether a subset of people may experience rare, delayed adverse events related to prolonged spike protein expression.
The Limitations—Stated Clearly
The researchers are transparent about the study’s weaknesses:
- Small sample size. Nineteen cases are a very small number.
- No definitive proof of vaccine origin. Asymptomatic infection cannot be ruled out in every case.
- Tissue sampling location. Samples came from around the hemorrhage, not the hemorrhage itself, making it difficult to establish causation.
- Retrospective design. Some vaccination records were incomplete; one case relied on family recollection.
- Single-center study. The findings have not yet been replicated elsewhere.
The authors repeatedly call for “global replication studies” to verify their observations.
What the Study Does Not Claim
It is important to be precise about what this paper does and does not argue.
The authors do not claim that mRNA vaccines cause hemorrhagic stroke. They explicitly state that “the relationship between hemorrhagic stroke and the expression of spike protein remains unclear.”
What they do claim is that spike protein can persist in cerebral artery walls for many months after vaccination, that it is associated with some inflammatory cell infiltration, and that this raises concerns about long-term biodistribution and safety that warrant urgent further investigation.
The Bigger Picture: An Unresolved Safety Question
This study arrives at a moment when public discussion of mRNA vaccine safety has become polarized. The authors stake out a position that is neither dismissive nor alarmist: they describe the vaccines as having demonstrated efficacy in clinical trials, but argue that long-term safety data are lacking precisely because the technology is so new.
Their central point is that the behavior of lipid nanoparticle-encapsulated mRNA in the human body—where it goes, how long it stays, and what it does in tissues far from the injection site—has not been adequately mapped.
The detection of spike protein in cerebral arteries up to 17 months post-vaccination, if confirmed, would represent a significant departure from the assumption that vaccine-produced protein is short-lived.
What Comes Next
The authors call for several specific steps:
- Larger, multi-center studies to confirm or refute their findings.
- Better methods to distinguish vaccine-derived spike protein from infection-derived spike protein.
- Investigation into sex-based differences in vaccine biodistribution and immune response.
- Long-term surveillance for rare neurological and cardiovascular events.
They also note that differentiating vaccine mRNA from viral RNA remains technically challenging and that improved detection tools are needed.
Takeaway Message
- A Japanese study detected SARS-CoV-2 spike protein in the walls of cerebral arteries in 43.8% of vaccinated hemorrhagic stroke patients, in some cases, 17 months after vaccination.
- Spike protein was found exclusively in female patients in this cohort, suggesting possible sex-based differences in vaccine response.
- Inflammatory immune cells were observed in spike-positive vessels, though no active vasculitis was found.
- Vaccine-derived mRNA was detected in arterial tissue in three cases, raising questions about how long vaccine material persists in the body.
- No nucleocapsid protein was detected, supporting the absence of active viral infection—though asymptomatic infection cannot be entirely ruled out.
- The study is small (19 cases) and cannot establish causation; the authors call for urgent global replication.
- The findings point to unresolved questions about lipid nanoparticle biodistribution and the long-term safety profile of mRNA vaccines.
- The authors emphasize that the actual behavior of mRNA vaccines in the human body may differ from prior assumptions and requires comprehensive investigation.
Don’t Get Sick!
About Dr. Jesse Santiano, MD
Dr. Santiano is a retired internist and emergency physician with extensive clinical experience in metabolic health, cardiovascular prevention, and lifestyle medicine. He reviews all medical content on this site to ensure accuracy, clarity, and safe application for readers. This article is for educational purposes and is not a substitute for personal medical care.
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References:
- Ota N, Itani M, Aoki T, Sakurai A, Fujisawa T, Okada Y, Noda K, Arakawa Y, Tokuda S, Tanikawa R. Expression of SARS-CoV-2 spike protein in cerebral Arteries: Implications for hemorrhagic stroke Post-mRNA vaccination. J Clin Neurosci. 2025 Jun;136:111223. doi: 10.1016/j.jocn.2025.111223. Epub 2025 Apr 3. PMID: 40184822. https://www.sciencedirect.com/science/article/pii/S096758682500195X
Disclaimer:
This article is for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your physician before making health decisions based on the TyG Index or other biomarkers.
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