Monitoring covid-19 Vaccine Safety: Assessing Adverse Events of Special Interest

Since the declaration of the COVID-19 pandemic by the World Health Organization (WHO) on March 11, 2020, over 13.5 billion doses of COVID-19 vaccines have been administered worldwide. This remarkable achievement in vaccine distribution highlights the urgent need for comprehensive vaccine safety monitoring, as very rare adverse events associated with COVID-19 vaccines may only become apparent after widespread administration.

To address this need, the Safety Platform for Emergency Vaccines (SPEAC) initiative formulated a list of potential COVID-19 vaccine adverse events of special interest (AESI) in 2020. These AESI were selected based on various factors, including their associations with immunization, vaccine platforms, or adjuvants, as well as theoretical concerns related to immunopathogenesis.

One flexible approach for assessing AESI is the comparison of observed AESI rates following vaccine introduction with expected rates based on historical periods pre-vaccine rollout. This method, known as observed vs. expected (OE) analysis, can rapidly detect potential vaccine safety signals. For example, OE analysis played a crucial role in identifying thrombosis with thrombocytopenia syndrome (TTS) as a safety signal, prompting the suspension of the AstraZeneca COVID-19 vaccine in certain countries.

To further enhance vaccine safety monitoring, a global cohort study was conducted as part of the Global COVID Vaccine Safety (GCoVS) Project. This project, funded by the Centers for Disease Control and Prevention (CDC), involves multiple nations and aims to monitor COVID-19 vaccine safety on a global scale.

Thirteen AESI were selected for evaluation, including neurological, hematologic, and cardiovascular conditions, which are as follows:

1. Guillain-Barré syndrome (GBS),
2. Transverse myelitis (TM),
3. Facial (Bell’s) palsy,
4. Acute disseminated encephalomyelitis (ADEM), 
5. Convulsions (generalized seizures (GS), 
6. Febrile seizures (FS),
7. Cerebral venous sinus thrombosis (CVST),
8. Splanchnic vein thrombosis (SVT),
9. Pulmonary embolism (PE),
10. Thrombocytopenia,
11. Immune thrombocytopenia (ITP),
12. Myocarditis
13. Pericarditis

These conditions were chosen based on their relevance to real-world vaccine pharmacovigilance and the availability of background rates generated by GCoVS sites.

The study analyzed data from 10 sites across eight countries, comprising a total vaccinated population of 99,068,901 individuals. Notable findings include a statistically significant increase in Guillain-Barré syndrome (GBS) cases following the administration of the ChAdOx1 (India) vaccine and an increased risk of acute disseminated encephalomyelitis (ADEM) after the mRNA-1273 vaccine (Moderna).

Hematologic conditions such as cerebral venous sinus thrombosis (CVST) and immune thrombocytopenia (ITP) also showed elevated risk ratios following certain vaccine doses. Similarly, cardiovascular conditions like myocarditis and pericarditis demonstrated increased risk ratios, particularly after mRNA vaccine doses (Pfizer, Moderna, AstraZeneca).

Here is the raw data collected from the study:

Here is a chart summarizing the raw data collected in the study:

Overall, these findings underscore the importance of ongoing vaccine safety monitoring and highlight the value of global collaboration in assessing vaccine-related adverse events. By leveraging methodologies such as OE analysis and conducting comprehensive cohort studies, public health agencies can swiftly detect and respond to potential vaccine safety signals, ensuring the continued safety and effectiveness of COVID-19 vaccination efforts worldwide.

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references

K. Faksova, et al. “COVID-19 Vaccines and Adverse Events of Special Interest: A Multinational Global Vaccine Data Network (GVDN) Cohort Study of 99 Million Vaccinated Individuals.” Vaccine, 1 Feb. 2024, https://doi.org/10.1016/j.vaccine.2024.01.100.