February 23, 2025, 3:06 pm | Read time: 6 minutes
Corona vaccines have saved millions of people worldwide from serious illness and death. Nevertheless, some people report long-lasting symptoms after vaccination, a phenomenon known as post-vaccination syndrome (PVS). A new study from Yale University now provides the first evidence of immunological changes that could be behind these symptoms. The results of the study could contribute to a better understanding of the syndrome and initiate targeted research into diagnostics and therapy. FITBOOK Editorial Director Melanie Hoffmann explains what the researchers have discovered.
The introduction of the coronavirus vaccine has made a significant contribution to containing the pandemic. But there are also reports of vaccine damage. Some people experienced persistent symptoms after vaccination, including chronic fatigue, neurological complaints, and inflammatory reactions. Until now, however, there has been little scientific knowledge about the possible biological mechanisms behind these symptoms. Scientists at Yale University wanted to change this. In fact, their study provides interesting insights into physical changes in people suffering from post-vaccination syndrome.
Overview
- Post-Vaccination Syndrome
- Are There Immunological Factors That Could Explain the Vaccination Damage?
- How the Study Was Structured
- Distinctive Findings in Post-Vaccination Syndrome Patients
- The Significance of the Study Results
- Possible Consequences of the Detected Changes
- Weaknesses and Strengths of the Study
- Conclusion
- Sources
Post-Vaccination Syndrome
The so-called post-vaccination syndrome (PVS) has not yet been clearly defined. Some of the symptoms are similar to those of long COVID, which is why it is difficult to establish causal links. The current study analyzed the immunological characteristics of those affected and compared them with healthy, vaccinated individuals in order to identify possible differences.
Are There Immunological Factors That Could Explain the Vaccination Damage?
The aim of the study was to identify potential immunological and antigenic characteristics in people with PVS. To this end, data from the Yale LISTEN study, an ongoing research initiative on the long-term effects of COVID-19 and vaccinations, were analyzed.1
Specifically, the Following Questions Were Investigated:
- Are there differences in immune cell profiles between PVS sufferers and healthy, vaccinated individuals?
- Is there evidence of viral reactivation, particularly of the Epstein-Barr virus (EBV)?
- Are higher levels of circulating spike proteins detectable in people with PVS?
- Are there differences in antibody responses to the vaccination?
How the Study Was Structured
The study was conducted as a decentralized, cross-sectional observational study. This means that the study represents a snapshot and cannot make any statements about changes over time.
Study Participants
- 42 people with PVS (symptoms lasting longer than six weeks after COVID-19 vaccination)
- 22 healthy vaccinated control subjects
The Methodology
- Analysis of immune cell profiles
- Measurement of antibody titers against the spike protein(titer is the unit of measurement for antibodies that indicates the dilution level, which is important for a positive antigen-antibody reaction A. d. R.2
- Detection of circulating spike proteins
- Examination for Epstein-Barr virus reactivation using serological markers
Distinctive Findings in Post-Vaccination Syndrome Patients
The study identified several significant differences between PVS sufferers and healthy vaccinated individuals:
Altered Immune Cell Profiles
PVS patients had a lower number of circulating memory and effector CD4 T cells (type 1 and type 2). These cells play an important role in immune defense.
At the same time, an increased number of TNFα+ CD8 T cells was detected, which could indicate an altered immune activity.
Lower Antibody Response
PVS sufferers had lower overall anti-spike antibody titers than the control group.
This difference was largely due to the fact that they had received fewer vaccine doses on average.
More Frequent Epstein-Barr Virus (EBV) Reactivation
Serologic evidence of recent EBV reactivation was found more frequently in people with PVS than in the control group. Epstein-Barr is a virus that is associated with autoimmune diseases and can also be reactivated after COVID-19 infections.
Detection of Circulating Spike Proteins
PVS sufferers had higher levels of circulating spike proteins than healthy, vaccinated individuals. This may indicate that the spike protein remains in the body longer after vaccination in some cases, but further studies are needed to clarify the significance of this finding.
The Significance of the Study Results
The study provides the first scientific evidence that post-vaccine syndrome is associated with specific immunological changes. The observed differences in immune cell populations, EBV reactivation, and persistent spike proteins could play a role in the persistent symptoms.
Possible Consequences of the Detected Changes
- Altered immune regulation: The reduction of memory T cells with a simultaneous increase in inflammatory CD8 T cells could indicate an altered immune response.
- Viral reactivation: EBV reactivations have also been observed in Long COVID and could contribute to persistent symptoms.
- Persistent spike proteins: The detection of circulating spike proteins in PVS sufferers suggests that the immune system may be exposed to the viral antigen for longer in some cases.
These results indicate potential mechanisms but are not sufficient to establish a clear cause-effect relationship.
Weaknesses and Strengths of the Study
The strengths of the study include that it included high-quality immune analysis to identify biological differences and looked at several possible mechanisms behind post-vaccination syndrome. The researchers examined immune cells, antibodies, Epstein-Barr virus reactivation, and spike proteins. They also included a control group of vaccinated people without vaccine damage, which allows for better comparability.
One of the weaknesses is the small sample, which comprised only 42 PVS sufferers and 22 control subjects. Therefore, the study results cannot be generalized. In addition, the cross-sectional study only shows associations but does not prove causality. This would require further research based on the current findings.
There is also a lack of comparative data from Long COVID patients to ensure that the changes observed are actually specific to post-vaccination syndrome. The interpretation of the study results is further complicated by the heterogeneous symptoms of the study participants. The PVS patients suffered from different symptoms.
It is also important to mention that the published Yale study is a preprint, which means that an independent review by other scientists is still pending.
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Conclusion
The study offers preliminary biological evidence suggesting a link between post-vaccination syndrome and specific immune changes. Particularly striking are the reduction of important immune cells, evidence of EBV reactivation, and the increased presence of circulating spike proteins.
Whether these factors play a direct role in the development of PVS or are merely accompanying symptoms must be investigated in further studies with larger numbers of participants. The results provide a valuable basis for future research into better diagnosis and possible treatment of PVS, on which further studies can now build. This was also emphasized by those responsible for the study themselves in a university press release about their research project.3