In a recent study published on the medRxiv * preprint server, researchers reported that contact between vaccinated people may affect the effectiveness of coronavirus vaccines 2019 (COVID-19).
Study: Higher contact among vaccinees may be a mechanism for negative vaccine efficacy. Image credit: BaLL LunLa / Shutterstock
Background
Early studies from the United Kingdom, Canada and Denmark observed a negative efficacy of the vaccine (VEff) against Omicron with severe acute coronavirus-2 (SARS-CoV-2) respiratory syndrome. VEff is determined by comparing infection levels between vaccinated and unvaccinated people.
Negative VEff reflects a higher infection rate among the vaccinated population than unvaccinated people. Vaccines are thought to increase biological sensitivity, ie. the virus evolved to spread rapidly among vaccinated subjects.
However, VEff calculations are based on observational data and are subject to variations 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 people (heterogeneity of vaccinated contacts) due to vaccine mandates limiting certain places for vaccinated people.
The study and findings
In the present study, the researchers assessed whether higher contact between vaccinated individuals could lead to negative VEff measurements and how this relationship was affected by vaccine efficacy (VEI) or susceptibility (VES). The VE reflects the reduced likelihood of vaccinees becoming infected, and the VEI indicates the reduced infectivity of vaccinees if a breakthrough infection occurs.
The authors implemented a simple model of transmission-susceptible, recovering (SIR) transmission dynamics, receiving an all-or-nothing vaccine. The SIR model consists of contact rates within the unvaccinated (cuu) and vaccinated people (cvv) class and interclass percentages for unvaccinated persons (cvu) and unvaccinated with vaccinated persons (cuv). In all simulations, a vaccination coverage of 75% was accepted. Two types of contact scenarios were assessed: 1) homogeneous contact, in which vaccinated and unvaccinated people have equal and random (proportional) contacts, and 2) heterogeneous contact, in which vaccinated subjects have higher intraclass contact.
For the homogeneous contact scenario, they adopted six contacts per person per day, specifying cuv = cvv = 4.5 and cvu = cuu = 1.5. They suggested a 50% increase in contacts for heterogeneous contact settings than in homogeneous scenarios. The recovery rate was set at 1/10 and the probability of transmission was 0.01, so the basic reproductive number (R0) was six for unvaccinated people. Baseline values for VES (0.5) and VEI (0.1) were adopted. The simulations were initiated by introducing one infected, vaccinated and unvaccinated person into the population. VEff for time t is calculated as VEff
The researchers did not observe a negative effect for VEff for homogeneous contact scenarios. However, heterogeneous contact scenarios generate negative VEff, although only when the efficacy of the vaccine is lower, i. when VES = VEI = 0.1 and VEI = 0.5, VES = 0.1. Negative VEff was evident only during the growth of the epidemic, but became positive when unvaccinated susceptible individuals were lower than the combined proportion of susceptible-vaccinated and immuno-vaccinated individuals. VEI moderately affects the minimum VEff, while VES and contact between vaccinated subjects severely affect it. A strongly negative VEff (less than -1) is observed when the VES is < 0.2 и cvv е 9. Въпреки че VEI е по-малко влиятелен върху VEff, по-високите нива на VEI (>0.92) do not cause a negative VEff even when the VES is lower (<0.1).
Conclusions
The present study showed that the heterogeneity of vaccinated contacts, ie. increased contact between vaccinated individuals may lead to a negative VEff, illustrating scenarios in which vaccines may not be useful. Vaccinated contact heterogeneity may adversely affect VEff measurements only when vaccine efficacy, especially VES, is lower. Researchers note that the efficacy of vaccines may mediate the effect of bias on contact heterogeneity.
In addition, negative VEff measurements were found only during an increase in the epidemic, when the number of susceptible unvaccinated people was lower than the vulnerable vaccinated population.
In previous empirical studies, negative VEff always coincided with the growth phase of the SARS-CoV-2 Omicron epidemic. In addition, other abnormalities, such as selection bias or higher immunity caused by infection in the unvaccinated population, may adversely affect VEff.
In conclusion, the researchers reported a plausible mechanism for negative VEff measurements despite useful vaccines and how deviations can be identified. Future work may be able to deal with other possible and potential deviations leading to a negative VEff.
*Important message
medRxiv publishes preliminary scientific reports that are not reviewed by partners and therefore should not be considered convincing, guide clinical practice / health-related behavior, or be treated as established information.
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