The ChAdOx1-S (Oxford-AstraZeneca) COVID-19 vaccine, celebrated for its efficacy, cost-effectiveness, and ease of handling, has faced scrutiny due to its association with cerebral venous thrombosis (CVT). This rare yet serious adverse event has prompted various countries to reconsider the vaccine’s usage, especially among younger demographics.
Association of CVT with ChAdOx1-S Vaccine
CVT, particularly in the context of the ChAdOx1-S vaccine, has been reported within 28 days of inoculation. It exhibits a distinct clinical profile, including symptoms of thrombosis with thrombocytopenia syndrome, and carries a significant mortality rate. A large portion of these cases can be attributed to vaccine-induced thrombotic thrombocytopenia (VITT), a condition known for its severe outcomes.
TABLE 1 – Vaccine-Induced Thrombotic Thrombocytopenia (VITT): A Detailed Report
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but serious adverse event that can occur following vaccination with certain adenoviral vector-based COVID-19 vaccines, primarily the AstraZeneca (ChAdOx1 nCoV-19) and Johnson & Johnson (J&J) vaccines.
What is VITT?
VITT is characterized by the combination of:
- Thrombosis: Blood clots that can occur in any part of the body, but most commonly in the brain (cerebral venous sinus thrombosis, CVST), abdomen (splanchnic vein thrombosis), and legs (deep vein thrombosis, DVT)
- Thrombocytopenia: Low platelet count, which increases the risk of bleeding
- Positive heparin-induced platelet factor 4 (PF4) antibody test: This test detects antibodies that target a complex of PF4 and heparin, even though heparin has not been used, suggesting an abnormal immune response
Symptoms of VITT
Symptoms of VITT can appear 4-30 days after vaccination and can include:
- Severe headache, especially persistent or worsening
- Vision problems, such as blurred vision or double vision
- Abdominal pain
- Nausea and vomiting
- Swelling or pain in the legs
- Difficulty breathing
Diagnosis of VITT
There is no single test for VITT, and diagnosis is based on a combination of clinical symptoms, laboratory findings, and imaging tests. The following are typically used:
- Blood tests: Platelet count, D-dimer levels, PF4-heparin ELISA test
- Imaging tests: CT scan or MRI of the brain, CT scan or ultrasound of the abdomen, CT scan or ultrasound of the legs
Treatment of VITT
Treatment for VITT is urgent and requires specialized care. It typically involves:
- Stopping any further doses of the adenoviral vector vaccine
- Administering anticoagulants to prevent further blood clots
- Administering intravenous immune globulin (IVIG) to suppress the immune response
- Plasma exchange, a procedure that removes harmful antibodies from the blood
Risk Factors for VITT
The exact risk of VITT is unknown, but it is estimated to be very low, on the order of 1-5 cases per 100,000 vaccinations. Certain factors may increase the risk of VITT, including:
- Age: VITT is more common in younger adults, particularly women
- Underlying medical conditions: Certain medical conditions, such as cancer, inflammatory bowel disease, and antiphospholipid syndrome, may increase the risk
- Previous heparin exposure: A history of heparin-induced thrombocytopenia (HIT) may increase the risk
Comparison with COVID-19
The risk of VITT from vaccination is much lower than the risk of developing blood clots or other serious complications from COVID-19 itself. Studies have shown that the benefits of COVID-19 vaccination far outweigh the risks, even in individuals with risk factors for VITT.
VITT is a rare but serious adverse event that can occur after vaccination with certain adenoviral vector-based COVID-19 vaccines. Early recognition and prompt treatment are essential for improving outcomes. However, the overall risk of VITT is very low, and the benefits of COVID-19 vaccination far outweigh the risks for most individuals.
- American Society of Hematology: https://www.hematology.org/covid-19
- Centers for Disease Control and Prevention (CDC): https://vaers.hhs.gov/
- National Institutes of Health (NIH): https://covid19.nih.gov/
- UpToDate: https://www.uptodate.com/contents/covid-19-vaccine-induced-immune-thrombotic-thrombocytopenia-vitt
Blood Group and COVID-19 Severity
Recent investigations have highlighted the potential role of blood type in determining the severity of COVID-19. Individuals with blood group A are reportedly at a higher risk of severe COVID-19 (odds ratio [OR] = 1.45), while those with blood groups B or O are underrepresented in severe cases. Additionally, patients with groups A and AB are more likely to require intensive care and mechanical ventilation compared to groups B or O. A groundbreaking GWAS in CVT patients revealed a threefold increase in CVT risk among non-O blood group individuals compared to those with blood type O.
Study on CVT After ChAdOx1-S Vaccination
A significant study involving 82 CVT patients post ChAdOx1-S vaccination and 441 non-vaccinated individuals of European descent was conducted. This study aimed to ascertain if specific ABO blood groups were more susceptible to CVT post-vaccination. The results were startling: blood group O was significantly more prevalent in the vaccinated CVT group compared to the unvaccinated group, indicating a higher susceptibility. Conversely, blood group A showed lower prevalence in the vaccinated group. The unadjusted model suggested that those with blood group O were three times more likely to develop CVT post-vaccination compared to group A.
Multivariate Analysis and Demographics
Further analysis, considering established CVT risk factors, corroborated these findings. The demographic analysis revealed no significant age and sex differences between vaccinated and unvaccinated CVT patients. Interestingly, over 80% of vaccinated patients with VITT-CVT were classified as Definite cases.
ABO Allele Frequencies and ChAdOx1-S Vaccination
The study also explored ABO allele frequencies in relation to the ChAdOx1-S vaccination. The data revealed a higher frequency of the O allele in vaccinated patients compared to unvaccinated ones. This suggests a potential genetic predisposition that might influence the risk of developing CVT post-vaccination.
In this discussion section, we will delve into the findings presented in the study, analyzing the implications of the data and the potential insights it offers into the relationship between blood groups, particularly blood group O, and the development of Cerebral Venous Thrombosis (CVT) in individuals who have received the ChAdOx1-S (Oxford-AstraZeneca) COVID-19 vaccine. We will also consider the limitations of the study and the broader implications of these findings in the context of vaccine-associated CVT.
Blood Group O Prevalence in VITT-CVT Cases
The study’s primary finding centers on the prevalence of blood group O among patients with Vaccine-Induced Thrombotic Thrombocytopenia and Cerebral Venous Thrombosis (VITT-CVT) after ChAdOx1-S vaccination, compared to unvaccinated CVT cases. The data reveal a significant difference in blood group distribution between these two groups.
Blood group O was found to be more common among vaccinated patients, with 63% (95% CI: 53–74) having this blood group, followed by allele A, present in 31% (95% CI: 22–41). In contrast, among the unvaccinated group, blood group A was the most common at 50% (95% CI: 47–54), with blood group O at 43% (95% CI: 40–47). This discrepancy in blood group distribution between the vaccinated and unvaccinated CVT cases is a crucial finding and suggests a potential link between blood group O and the development of CVT following ChAdOx1-S vaccination.
Significance of the Study
The rarity of VITT-CVT post-COVID-19 vaccination is acknowledged, and the study’s significance lies in the fact that it presents one of the largest cohorts of such cases, drawing from two international ongoing studies. This is essential for studying a rare condition like VITT-CVT, as it allows for a more comprehensive analysis of the data.
Blood Group’s Role in CVT and Vaccination-Associated CVT
The study draws attention to the growing body of evidence implicating blood groups in CVT, both in terms of onset and outcome. The data presented in this study suggests that blood group may also play a role in the development of CVT after vaccination. The implications of this finding are twofold. Firstly, it suggests a potential etiological mechanism for CVT after receiving a vector-based vaccine like ChAdOx1-S. Secondly, it may assist in identifying individuals who are more susceptible to this rare adverse event.
The European Medicines Agency’s indication that young people with blood group O may experience immunosenescence after ChAdOx1-S vaccination, leading to blood abnormalities resembling disseminated intravascular coagulation, adds depth to the discussion. This implies that blood group antigens play a direct role in infection, and specific blood types may have varying responses to the vaccine.
The role of anti-A antibodies in protecting against the uptake of the severe acute respiratory syndrome coronavirus 1 and the inhibition of cellular adhesion by blood group A with anti-A antibodies further underscores the potential relevance of blood groups in the context of vaccination-associated CVT.
Limitations of the Study
While the data presented in this study are compelling, it is essential to acknowledge its limitations. First and foremost, the study’s sample size for patients who received ChAdOx1-S was limited due to the rarity of CVT after vaccination. However, given the rarity of CVT itself and the even rarer occurrence of vaccination-associated CVT, this study still represents one of the most extensive investigations of its kind.
Other potential limitations include the presence of confounding factors, such as genetic or environmental variables that were not accounted for in the analysis. Additionally, the study acknowledges that the ChAdOx1-S vaccine was administered in a vast number of doses in a relatively short period, making it crucial to consider potential side effects within this context.
In conclusion, this study provides valuable insights into the association between blood groups, particularly blood group O, and the development of CVT following ChAdOx1-S vaccination. While the findings are significant, further research is needed to validate and expand upon these results, considering the limitations highlighted in this discussion. Nevertheless, this study represents a critical step in understanding the complex relationship between blood groups and the rare adverse events associated with COVID-19 vaccination.
reference link : https://journals.sagepub.com/doi/10.1177/01410768231214341