Some COVID-19 Vaccine Adverse Effects May Be Driven by Preexisting Hesitancy

Varying public messaging techniques based on the population the messaging seeks to reach is needed to address COVID-19 vaccine hesitancy fueled by inaccurate beliefs regarding adverse effects (AEs), according to a study published in Scientific Reports.

Prior to the COVID-19 pandemic, vaccine hesitancy was listed among to the 10 greatest global threats to public health by the World Health Organization. The authors of the current study note that vaccine hesitancy differs from an antivax stance because it often results in vaccination, whereas antivax typically leads to refusal because it is largely motivated by ideological, political, and religious beliefs.

However, both vaccine hesitancy and antivax beliefs are fueled by inaccurate reports of AEs from vaccines, according to the study. The investigators noted that questions persist in the directionality of the link between AEs and vaccine hesitancy regarding which variable is predictive of the other.

They speculate that AEs from an earlier dose of the COVID-19 vaccine may be associated with vaccine hesitancy for the subsequent dose. Conversely, hesitancy to the initial dose may predict AEs from the later dose. This reflects the nocebo effect, which are AEs driven by psychological factors instead of an actual component of active treatment, according to the study authors.

For the study, researchers from Bar-Ilan University and Ariel University in Israel evaluated vaccine hesitancy in 750 older adults. This population was chosen because they have a high vaccination rate coupled with low AEs, which makes detecting nocebo effects more difficult, according to the investigators.

To overcome this issue, the researchers sought to address both vaccine hesitancy and AEs at 2 different time points—immediately following the second vaccine dose and 6 months after the booster dose. Next, they evaluated whether wave-1 AEs predict wave-2 hesitancy or wave-1 hesitancy predicts wave-2 AEs.

The investigators found that wave-1 hesitancy was predictive of wave-2 AEs. Specifically, they said that prior vaccine hesitancy for the second COVID-19 dose was predictive of nocebo AEs for the booster dose.

According to the study authors, up to 16% of vaccine AEs were explained by prior vaccine hesitancy. They added that the nocebo effect in women was more greatly affected by experience, with the link between prior and current AEs twice as large in women compared with men. These findings highlight the current flaws in public health messaging, which the investigators said typically targets unvaccinated individuals with messaging that stresses the safety of vaccines.

"Such public health messaging may for example be less suited to those who received a vaccination dose and have electively chosen to discontinue vaccination. In the United States alone there are over 150 million such persons," lead study author Yaakov Hoffman, professor from the Interdisciplinary Department of Social Sciences at Bar-Ilan University, said in a press release.

According to the investigators, messaging should be tailored to address individuals with different risk levels. For example, tailoring messages for a low-risk population emphasizing that the vaccine is safer for them as individuals than it is for the general public may be effective.

"For such persons messaging focused on general vaccination safety may be less applicable to partially-vaccinated individuals who have first-hand experience with vaccine side effects and electively chose to discontinue vaccination. Rather differentiated public health messaging is required," said co-author prof. Menachem Ben-Ezra, of Ariel University, in a press release.

However, for high-risk level populations, it may be more effective to provide messaging that emphasizes a significant portion of AEs are not related to vaccination.

“Conveying that COVID-19 vaccine side effects may be driven by anxiety or a previous negative expectation may be extremely effective,” the study authors wrote. “Such messaging should be coupled with nocebo education conveying that these experienced side effects are just as physically real, yet may not stem from treatment but from other factors.”

These findings suggesting that vaccination AEs comprise nocebo effects may be an important factor to facilitate effective public messaging delivered in an accepting, humane, and non-paternalistic manner, according to the study authors. Such a strategy may help to reduce both the nocebo effect and AEs experienced.

"Most importantly, as COVID-19 may still be a threat and vaccines are still offered, public health messaging should consider addressing the issue that side effects comprise a nocebo component," Hoffman said.

Reference

Hoffman, Y.S.G., Levin, Y., Palgi, Y. et al. Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination. Sci Rep 12, 20018 (2022). https://doi.org/10.1038/s41598-022-21434-7