Contact Heterogeneity Could Produce Negative Vaccine Efficiency

Infection from the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, may have produced negative measurements of vaccine efficiency due to different methods of contact (contact heterogeneity) among vaccinated individuals, and this could have biased observational studies of vaccine efficiency, according to findings published in American Journal of Epidemiology.

Negative vaccine effectiveness for COVID-19, which was calculated by comparing the rates of infection between vaccinated and unvaccinated individuals, has been reported in 6 studies from Canada, Denmark, and the United States. These findings suggest that vaccinated individuals were contracting COVID-19 at higher rates than unvaccinated individuals. Contact heterogeneity, such as increased contact between vaccinated individuals due to policies that restricted spaces to vaccinated individuals, is defined as different levels of contact between population subgroups. This study aimed to assess whether vaccinated contact heterogeneity and levels of vaccine efficacy against susceptibility (VE_S) and vaccine efficacy against infectiousness (VE_I) produced negative vaccine efficacy.

The researchers built a compartmental susceptible, exposed, infectious, recovered (SEIR) transmission dynamics model for this study that included vaccinated and unvaccinated individuals. All simulations assumed there was 75% vaccination coverage. Homogeneous contact and heterogeneous contact were explored.

Homogeneous contact assumed there were 6 daily contacts per person, which was an approximate contact rate based on the United States and United Kingdom. Contacts were increased by 50% in the heterogeneous contact scenario vs the homogeneous contact. Rate of recovery was 1/10, rate of progression from exposed to infectious was 1/4, and the probability of transmission was 0.01.

The researchers found that the different contact patterns based on vaccination status and level of vaccine efficacies were able to influence the existence and degree of bias when measuring vaccine efficiency. Homogeneous contact scenarios produced accurate measurements of vaccine efficiency (vaccine efficiency = VE_S) and never led to underestimation or negative vaccine efficiency.

However, heterogeneous contact scenarios defined by vaccination status consistently produced underestimated vaccine efficiency, but only in the context of lower vaccine efficiencies (VE_S = 0.1, VE_I = 0.1, and VE_S = 01; VE_I = 0.5). The effect of vaccinated contact heterogeneity on vaccine efficiency measurements was reduced by vaccine efficacies; however, moderately high vaccine efficacies (VE_S = VE_I = 0.7) produced underestimations of vaccine efficiency when contact heterogeneity was high.

Measurements of vaccine efficiency varied over time due to vaccinated individuals' contact heterogeneity. The highest underestimations in the heterogeneous contact measurements and the measurements of negative vaccine efficiency occurred during epidemic growth. Vaccine efficiency only produced positive results when the proportion of unvaccinated was lower than the combined proportion of vaccinated while immune due to vaccination. SEIR transmission dynamics also had consistent infection and vaccine efficiency results.

The sensitivity analysis found that VE_I had a moderate influence and VE_S had a strong influence on the maximum negative vaccine efficiency. Increasing contact between vaccinated individuals was generally found to lead to underestimations.

The researchers concluded that their study found a “potential mechanism for negative vaccine efficiency measurements found for the Omicron variant” and provided “a potential explanation for observed negative vaccine efficiency in future studies.”

Reference

Bodner K, Knight J, Hamilton MA, Mishra S. Testing if higher contact among vaccinated can be a mechanism for observed negative vaccine effectiveness. Am J Epidemiol. Published March 9, 2023. doi:10.1093/aje/kwad055