Study: Higher contact between vaccinated people may be a mechanism for negative vaccine efficacy. Image credit: BaLL LunLa / Shutterstock
Record
Early studies from the United Kingdom, Canada, and Denmark have shown a negative vaccine efficacy (VEff) against severe acute coronavirus-2 (SARS-CoV-2) Omicron variant syndrome. VEff is determined by comparing infection rates between vaccinated and unvaccinated individuals. A negative VEff reflects a higher rate of infection among the vaccinated population than the unvaccinated individuals. It has been suggested that vaccines enhance biological susceptibility, that is, the virus evolved to spread rapidly among vaccinated individuals. However, VEff calculations are based on observational data and are subject to bias, such as differential detection / testing and exposure between vaccinated and unvaccinated individuals. Contact heterogeneity is the different levels of contact in a population. For example, higher contact between vaccinated individuals (vaccine contact heterogeneity) due to vaccine orders restricting certain spaces for vaccinated individuals.
The study and the findings
In the present study, the researchers evaluated whether higher contact between vaccinated individuals could lead to negative VEff measurements and how this correlation is affected by the effectiveness of the vaccine against infectivity (VEI) or susceptibility (VES). VEs reflect the reduced chance of infection from the vaccinated and the VEI indicates reduced infectivity of the vaccinated if a new infection occurs. The authors applied a simple compartmental, sensitive, infectious, recovered dynamic transmission (SIR) model assuming a “all or nothing” type of vaccine. The SIR model consisted of contact rates within the class of unvaccinated (cuu) and vaccinated individuals (cvv) and percentages between classes for vaccinated non-vaccinated individuals (cvu) and non-vaccinated individuals (cuv). 75% vaccination coverage was assumed in all simulations. Two types of contact scenarios were evaluated: 1) homogeneous contact in which vaccinated and unvaccinated individuals have equal and random (proportional) contacts and 2) heterogeneous contact in which vaccinated individuals have higher contact within the class. For the homogeneous contact scenario, they assumed six contacts per person per day, defining cuv = cvv = 4.5 and cvu = cuu = 1.5. They assumed a 50% increase in contacts for heterogeneous contact settings than in homogeneous scenarios. The recovery rate was set at 1/10 and the transmission probability at 0.01, so that the baseline reproduction number (R0) was six for unvaccinated individuals. The base values for VES (0.5) and VEI (0.1) were adopted. The simulations began with the introduction of an infected, vaccinated and unvaccinated individual into the population. The VEff for time t was calculated as VEff The researchers did not observe a negative VEff for homogeneous contact scenarios. However, heterogeneous contact scenarios produced negative VEff, if and only when the vaccine efficacy was lower, e.g., when VES = VEI = 0.1 and VEI = 0.5, VES = 0.1. A negative VEff was only apparent during the outbreak, but became positive when unvaccinated susceptible individuals were lower than the combined proportion of susceptible-vaccinated and immunocompromised individuals. VEI had a moderate effect on the minimum VEff, while VES and contact between vaccinated individuals had a strong effect. A strongly negative VEff (less than -1) was observed when the VES was < 0,2 και το cvv ήταν 9. Αν και το VEI είχε μικρότερη επιρροή στο VEff, τα υψηλότερα επίπεδα VEI (>0.92) did not produce negative VEff even when the VES was lower (<0.1).
conclusions
The present study showed that heterogeneity of vaccinated contact, i.e. increased contact between vaccinated individuals, could lead to a negative VEff, illustrating scenarios where vaccines could be unhelpful. Heterogeneity of vaccinated contact could adversely affect VEff measurements only when vaccine efficacy, particularly VES, was lower. The researchers observed that the effectiveness of the vaccines could mediate the effect of preventing contact heterogeneity. In addition, negative VEff measurements were found only during the outbreak of the epidemic, when the number of susceptible unvaccinated individuals was lower than the susceptible vaccinated population. In previous empirical studies, the negative VEff always coincided with the developmental stage of the SARS-CoV-2 Omicron epidemic. In addition, other biases such as selectivity bias or higher infection-induced immunity among the unvaccinated population could adversely affect VEff. In conclusion, the researchers reported a reasonable mechanism for negative VEff measurements despite the beneficial vaccines and how the biases could be detected. Future work may be able to address other potential and potential biases that will lead to a negative VEff.
*Important note
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