Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination

Abstract

The directionality between vaccine hesitancy and COVID-19 vaccine side-effects has not been hitherto examined. We hypothesized a nocebo effect, whereby vaccine hesitancy towards the second Pfizer vaccination dose predicts subsequent side-effects for a booster dose, beyond other effects. We expected these nocebo effects to be driven by (mis)information in males and prior experience in females. A representative sample of older adults (n = 756, mean age = 68.9 ± 3.43) were questioned in a typical cross-lagged design (wave 1 following a second Pfizer dose, wave 2 after their booster). As hypothesized, earlier vaccine hesitancy predicted subsequent booster side-effects for females (β = 0.10 p = 0.025, f 2 = 0.02) and males (β = 0.34, p < 0.001, f 2 = 0.16); effects were stronger in males (χ2Δ (1) = 4.34, p = 0.03). The (W1-to-W2) side-effect autoregression was stronger in females (β =.34, p < 0.001; males β = 0.18, p < 0.001), χ2Δ (1) = 26.86, p < 0.001. Results show that a quantifiable and meaningful portion of COVID-19 vaccine side-effects is predicted by vaccine hesitancy, demonstrating that side-effects comprise a psychosomatic nocebo component in vaccinated individuals. The data reveal distinct risk levels for future side-effects, suggesting the need to tailor public health messaging.