Novel Robust Methodology for VAERS Analysis Reveals Very High Risk of Myocarditis and Pericarditis Following Dose 2 and Dose 3: #PathogenicPriming

Risk found of people under 30 is especially a concern because it was so rarely seen prior to 2021.

A new study published in the Journal of Evidence-Based Medicine by Daoyuan Lai and colleagues, a team of researchers from the University of Hong Kong, has made significant strides in understanding the safety of COVID-19 mRNA vaccines, particularly in relation to myocarditis risk after vaccination. The study may also represent a watershed moment in the methodology used to assess causality using VAERS data.

The study, which focuses on the rare but concerning risk of myocarditis following the administration of COVID-19 mRNA vaccines, introduces a novel approach to analyzing vaccine safety data that could transform how we monitor vaccine adverse events.

The study analyzed data from the US Vaccine Adverse Event Reporting System (VAERS), a resource that has been used to monitor post-vaccination adverse events. Recognizing the limitations of data in VAERS, including potential underreporting and the absence of a control group, the team employed a modified version of the Self-Controlled Case Series (SCCS) method. This innovative approach allowed for more accurate detection and quantification of myocarditis risk following the second and third doses of mRNA COVID-19 vaccines.

Key Findings:

• The research identified an increased risk of myocarditis within the 1- to 3-day period following the second and third doses of both the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines.

• Following the second dose, the relative incidence of myocarditis was 4.89 for the Pfizer-BioNTech vaccine and 2.86 for the Moderna vaccine. The risk increased following the third dose, with a relative incidence of 9.04 for Pfizer-BioNTech and 4.71 for Moderna.

• A similar increased risk of myocarditis was observed among individuals aged below 30.

The team's modified SCCS method accounts for potential underreporting in VAERS data and enables a more accurate assessment of the temporal association between vaccination and myocarditis. This methodological innovation nhances the study’s reliability and may offer a blueprint for future vaccine safety research.

The modified Self-Controlled Case Series (SCCS) method, developed by researchers like Daoyuan Lai and colleagues at the University of Hong Kong, is a powerful tool used to study the safety of vaccines, including the COVID-19 mRNA vaccines. At its core, the method offers a clever way to look at medical data to find out if and when certain vaccines might lead to rare side effects, such as myocarditis (a condition where the heart muscle becomes inflamed).

Here's why the modified SCCS method stands out, especially for studying vaccine safety:

Turns Limitations into Strengths: Traditional ways of studying vaccine safety often bump into problems like not having a proper group to compare against (since it's not ethical to withhold vaccines for a control group) and difficulty in accounting for the fact that some health issues after vaccination might just be coincidental. The modified SCCS method cleverly navigates these issues by focusing solely on those who experienced side effects, comparing their risk at different times to their own risk at other times. This way, it eliminates the need for a comparison group.

Cuts Through the Noise: Everyone is unique, and factors like age, gender, or underlying health conditions can affect the risk of side effects. The SCCS method automatically controls for these factors since it compares individuals to themselves over time, not to other people. This means the results are cleaner and more accurate because these differences among people do not muddle them.

Addresses Reporting Biases: One big challenge with vaccine safety data, especially from systems like VAERS, is that not all side effects are reported, and those reported might not be evenly distributed over time. The modified SCCS method incorporates a way to control for this uneven reporting, making it more likely to reveal the true relationship between vaccination and side effects.

Flexible and Insightful: This method is adaptable and can be tweaked to study different vaccines, side effects, and time frames. This flexibility allows researchers to gain insights into the safety of vaccines across various contexts and populations.

The modified SCCS method appears to add significantly to the toolbox of individuals analyzing VAERS data in search of causal inferences. Although limited to multi-dose exposures (boosters), it allows researchers to cut through the clutter of real-world data, control for biases and individual differences, and come up with clear, reliable insights into how vaccines might be linked to rare side effects.

#PathogenicPriming

Lai D, Lim D, Lu J, Wang H, Huang T, Zhang YD. 2024. Risk of myocarditis after three doses of COVID-19 mRNA vaccines in the United States, 2020-2022: A self-controlled case series study. J Evid Based Med. 17(1):65-77. doi: 10.1111/jebm.12595. Epub 2024 Mar 17. PMID: 38494781.