Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study

Figures

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  Fig. 1. Risk of Anaphylaxis Following XBB.1.5-containing COVID-19 mRNA Vaccination, Adjusted for COVID-19 Infection and Temporal Trends. Notes: Anaphylaxis was studied separately. Event counts fewer than 20 were replaced with “< 20” in accordance with N3C regulation. IRR indicates incidence rate ratio, calculated using conditional Poisson regression. The primary analysis included patients who received either brand of the XBB.1.5-containing COVID-19 mRNA vaccine and experienced anaphylaxis. The model was adjusted for COVID-19 infection and temporal trends.

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  Fig. 2. Risk of Adverse Events within 28 Days Following XBB.1.5-containing COVID-19 mRNA Vaccination, Adjusted for COVID-19 Infection and Temporal Trends. Notes: Each outcome was studied separately. Encephalitis was omitted because it was not observed with significant cases in this study. Events fewer than 20 were replaced with ‘< 20’ in accordance with N3C regulation. IRR indicates incidence rate ratio, calculated using conditional Poisson regression. The primary analysis included patients who received either brand of the XBB.1.5-containing COVID-19 mRNA vaccines and experienced specific outcomes. The model was adjusted for COVID-19 infection and temporal trends.

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  Fig. 3. Risk of Adverse Events within 28 Days Following XBB.1.5-containing COVID-19 mRNA Vaccination by Vaccine Brand, Adjusted for COVID-19 Infection and Temporal Trends. Notes: Each outcome was studied separately. Encephalitis was omitted because it was not observed with significant cases in this study. Event counts fewer than 20 were replaced with ‘< 20’ in accordance with N3C regulation. IRR indicates incidence rate ratio, calculated using conditional Poisson regression. The primary analysis included patients who received either brand of the XBB.1.5-containing COVID-19 mRNA vaccines and experienced specific outcomes. This subgroup analysis was stratified by vaccine brands. The model was adjusted for COVID-19 infection and temporal trends. NE, not estimable.

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  Fig. 4. Overview of the Self-controlled Case Series Study Design. Notes: The main risk period was days 0–2 for anaphylaxis and days 1–29 for other outcomes following XBB.1.5-containing COVID-19 mRNA vaccination. The reference period included both a pre-vaccination and post-vaccination time frame. The pre-vaccination period started 29 days after a previous non-XBB.1.5-containing COVID-19 vaccine and ended 14 days before the XBB.1.5-containing vaccination. The 28-day gap was included to minimize the influence of prior vaccinations. A 14-day pre-exposure window was excluded to prevent bias from event-dependent exposure. The post-vaccination period began immediately after the defined risk period and continued until the end of the study.

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  Fig. 5. Flowchart of patient selection and numbers in the N3C dataset (September 11, 2023 – June 1, 2024). Note: 1: The washout period for anaphylaxis was 30 days, and for other outcomes, 365 days. 2: According to N3C data policy, any cell size less than 20 must be redacted and replaced with ‘< 20’.