Expression of SARS-CoV-2 spike protein in cerebral Arteries: Implications for hemorrhagic stroke Post-mRNA vaccination, 2025, Ota et al

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Expression of SARS-CoV-2 spike protein in cerebral Arteries: Implications for hemorrhagic stroke Post-mRNA vaccination

Nakao Ota, Masahiko Itani, Tomohiro Aoki, Aki Sakurai, Takashi Fujisawa, Yasuaki Okada, Kosumo Noda, Yoshiki Arakawa, Sadahisa Tokuda, Rokuya Tanikawa

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Highlights
• Spike protein expression was detected in 43.8% of vaccinated patients.
• SARS-CoV-2 spike protein persists in cerebral arteries up to 17 months post-vaccination.
• Spike protein was expressed in the intima of the cerebral arteries.
• In situ hybridization confirmed vaccine- and virus-derived spike protein mRNA.
• Findings highlight concerns about mRNA vaccine biodistribution and long-term safety.

Background
The rapid deployment of mRNA vaccines for SARS-CoV-2, such as BNT162b2 (BioNTech-Pfizer) and mRNA-1273 (Moderna), provided a critical tool in combating the COVID-19 pandemic. While their short-term safety and efficacy were demonstrated in clinical trials, rare adverse events, including hemorrhagic strokes, have been reported after widespread use. However, the long-term biodistribution and effects of mRNA vaccines remain underexplored. This study aimed to investigate the long-term presence of SARS-CoV-2 spike protein in brain tissues of patients with hemorrhagic strokes, examining its potential association with mRNA vaccination.

Methods
A total of 19 cases of hemorrhagic stroke from 2023 to 2024 were retrospectively analyzed. Immunohistochemical staining for SARS-CoV-2 spike protein and nucleocapsid protein was performed on tissue samples. In situ hybridization was conducted in selected cases to confirm the origin of spike protein expression (vaccine or viral infection). Vaccination history and SARS-CoV-2 infection status were documented for all cases.

Results
Spike protein expression was detected in 43.8 % of vaccinated patients, predominantly localized to the intima of cerebral arteries, even up to 17 months post-vaccination.

While no active inflammatory changes were identified, infiltration of CD4-, CD8- and CD68- positive cells was observed in the spike protein positive vessels.

In situ hybridization confirmed the presence of both vaccine-derived mRNA and SARS-CoV-2 virus-derived mRNA, which encode the spike protein, in select cases.

Notably, spike protein positivity was observed exclusively in female patients (P = 0.015).

None of the cases showed nucleocapsid protein positivity, supporting the absence of active viral infection.

Conclusion
Although the possibility of spike protein expression due to asymptomatic SARS-CoV-2 infection cannot be entirely excluded, this study demonstrated prolonged presence of SARS-CoV-2 spike protein in the cerebral arteries following mRNA vaccination.

Additionally, some inflammatory cell infiltration was observed in spike-positive vessels.

These findings raise significant concerns regarding the biodistribution of lipid nanoparticle-based vaccines and their long-term safety. Global replication studies are urgently required to validate these findings and ensure comprehensive safety evaluations of mRNA vaccines.

Link | PDF (Journal of Clinical Neuroscience) [Open Access]
 
SARS-CoV-2 infection history was confirmed only for cases where patients had been diagnosed as positive via polymerase chain reaction (PCR) test or antigen testing at a medical institution. Therefore, cases with mild cold-like symptoms or undiagnosed infections due to the absence of medical consultation were considered as having no history of SARS-CoV-2 infection.
Is this is a reasonable assumption to make? Most infections are mild or asymptomatic, and rarely require a medical consult.
5. Limitation of the study
In our study, in situ hybridization detected both mRNA derived from the vaccine and mRNA from the SARS-CoV-2 virus. This suggests that the observed spike protein positive staining in patients with a history of SARS-CoV-2 vaccination, but no documented history of viral infection, cannot definitively be attributed to the vaccine alone. Notably, the nucleocapsid protein was consistently negative across cases, supporting the notion that our in situ hybridization method has high sensitivity and could detect trace amounts of mRNA, possibly reflecting unrecognized asymptomatic infections.
They can’t be attributed one way or another, period.
These findings emphasize the need for caution in interpreting the presence of spike protein as exclusively vaccine-related.
It seems to me like this should not have been a study on the vaccine. It should have been a study on the presence of spike protein.
 
It seems to me like this should not have been a study on the vaccine. It should have been a study on the presence of spike protein.

If I'm understanding correctly, it seems like in three cases they were able to show spike derived specifically from the vaccine in the brain. All three of whom had received the vaccine at least 11 months ago. I guess for that part specifically, it doesn't really matter if they were infected if their goal is to show that vaccine proteins can stick around.
In situ hybridization was conducted using control probes, SARS-CoV-2 vaccine mRNA-specific probes, and spike protein mRNA probes for Cases 4, 5, and 15. These cases showed positive staining for the SARS-CoV-2 spike protein and negative for the nucleocapsid protein in immunohistochemical staining. It had been 17, 12, and 11 months since their last mRNA-1273 or BNT162b2 vaccination. In all three cases, in situ hybridization revealed the presence of both mRNA from the vaccine and SARS-CoV-2 viral RNA in the intima
 
If I'm understanding correctly, it seems like in three cases they were able to show spike derived specifically from the vaccine in the brain. All three of whom had received the vaccine at least 11 months ago. I guess for that part specifically, it doesn't really matter if they were infected if their goal is to show that vaccine proteins can stick around.
They found mRNA from both the virus and the vaccine in the three cases where they actually tested the mRNA. I don’t believe they tested the other cases, so they can’t know if the staining was caused by the vaccine or the virus or both.

My understanding of this subject is very limited, but I also don’t believe that they found any evidence that the spike protein (regardless of source) actually caused any hemorrhagic strokes.

So the neutral angle for this study would have been:
We had access to tissue samples from the brain because someone did surgeries on stroke patients. We found evidence of spike protein from both the virus and vaccine long after any known infections and vaccinations.​

Everything else seems like an attempt to spin a story.
 
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