Global Study Shows Elevated Relative Risks of Certain Adverse Events After COVID-19 Vaccination

In April 2024, one of the largest COVID-19 vaccine safety studies to date was published in Vaccine:

“COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals” (Faksova et al., 2024).

This study analyzed nearly 99 million vaccinated individuals across 10 sites in eight countries, examining 13 neurological, hematological, and cardiac conditions that could occur after COVID-19 vaccination.

Study Design

Faksova and colleagues (2024) conducted a multinational observational cohort study, comparing observed versus expected (OE) rates of adverse events within 42 days after vaccination.

• Vaccines included:

  • Pfizer/BioNTech BNT162b2 (≈183.6 million doses)

  • Moderna mRNA-1273 (≈36.2 million doses)

  • AstraZeneca ChAdOx1 (≈23.1 million doses)

• Expected rates were derived from pre-COVID-19 healthcare data.

• Observed rates came from real-world data collected during vaccine rollout.

• A safety signal was defined if the lower bound of the 95% confidence interval (LBCI) for the OE ratio was greater than 1.5.

Understanding OE Ratio

The Observed-to-Expected (OE) ratio is a method to determine if an adverse event occurs more frequently than normal:

• Observed: How many cases actually occurred after vaccination.

• Expected: How many cases would normally occur in the same population without vaccination.

• OE ratio >1 → event occurs more often than expected

• OE ratio =1 → event occurs as expected

• OE ratio <1 → event occurs less often than expected

To make it easier for readers, OE ratios can be expressed as percent increase over expected:

Percent Increase=(OE ratio−1)×100\text{Percent Increase} = (\text{OE ratio} - 1) \times 100Percent Increase=(OE ratio−1)×100

Main Findings: Percent Increase in Risk

The study identified statistically significant increases in certain adverse events compared to what would normally be expected:

ConditionVaccineOE Ratio (95% CI)Percent Increase Over ExpectedGuillain-Barré syndrome (GBS)ChAdOx12.49 (2.15–2.87)149%Cerebral venous sinus thrombosis (CVST)ChAdOx13.23 (2.51–4.09)223%Acute disseminated encephalomyelitis (ADEM)mRNA-12733.78 (1.52–7.78)278%Myocarditis / PericarditisBNT162b2, mRNA-1273, ChAdOx1>1.5 LBCI>50%

Interpretation:

• GBS occurred 149% more often than expected after the first dose of ChAdOx1.

• CVST occurred 223% more often than expected.

• ADEM occurred 278% more often than expected after Moderna’s first dose.

• Myocarditis and pericarditis occurred at least 50% more often than expected across all three vaccines, although the exact number of cases was not reported.

What This Means

• The study confirms statistical increases (relative risk) in certain neurological and cardiac adverse events following COVID-19 vaccination.

• The study does not report absolute case counts or incidence rates (e.g., per 100,000 or per million doses).

• Without absolute numbers, it is impossible to determine the actual frequency of these conditions in the population from this study alone.

Ethical and Scientific Importance

• Public communication about vaccine safety must rely on quantitative evidence, not assumptions or qualitative labels like “rare” or “common.”

• When absolute numbers are missing, transparency is crucial: the public must know what the study shows and what it does not show.

• This study adds to global pharmacovigilance efforts, helping researchers monitor trends in vaccine safety while respecting scientific rigor and public trust.

Summary

• Faksova et al. (2024) analyzed data from nearly 99 million vaccinated people worldwide.

• Certain adverse events, including GBS, CVST, ADEM, myocarditis, and pericarditis, showed statistically significant increases relative to expected rates.

• The study did not provide absolute numbers or incidence rates, so exact risk in the population is unknown from this publication alone.

• This research highlights the importance of continued monitoring, but absolute safety or risk estimates require additional data.

Reference (APA 7th edition)

Faksova, K., Walsh, D., Jiang, Y., Griffin, J., Phillips, A., Gentile, A., Kwong, J. C., Macartney, K., Naus, M., Grange, Z., Escolano, S., Sepulveda, G., Shetty, A., Pillsbury, A., Sullivan, C., Naveed, Z., Janjua, N. Z., Giglio, N., Perälä, J., … Hviid, A. (2024). COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals. Vaccine, 42(9), 2200–2211. https://doi.org/10.1016/j.vaccine.2024.01.100