Background Google Trends is an infoveillance tool widely used by the scientific community to investigate different user behaviors related to COVID-19. However, several limitations regarding its adoption are reported in the literature. Objective This paper aims to provide an effective and efficient approach to investigating vaccine adherence against COVID-19 via Google Trends. Methods Through the cross-correlational analysis of well-targeted hypotheses, we investigate the predictive capacity of web searches related to COVID-19 toward vaccinations in Italy from November 2020 to November 2021. The keyword “vaccine reservation” query (VRQ) was chosen as it reflects a real intention of being vaccinated (V). Furthermore, the impact of the second most read Italian newspaper (vaccine-related headlines [VRH]) on vaccine-related web searches was investigated to evaluate the role of the mass media as a confounding factor. Fisher r-to-z transformation (z) and percentage difference (δ) were used to compare Spearman coefficients. A regression model V=f(VRH, VRQ) was built to validate the results found. The Holm-Bonferroni correction was adopted (P*). SEs are reported. Results Simple and generic keywords are more likely to identify the actual web interest in COVID-19 vaccines than specific and elaborated keywords. Cross-correlations between VRQ and V were very strong and significant (min r²=0.460, P* 55.8%; z>5.8; P*<.001). The regression model confirmed the greater significance of VRQ versus VRH (P*<.001 vs P=.03, P*=.29). Conclusions This research provides preliminary evidence in favor of using Google Trends as a surveillance and prediction tool for vaccine adherence against COVID-19 in Italy. Further research is needed to establish the appropriate use and limits of Google Trends for vaccination tracking. However, these findings prove that the search for suitable keywords is a fundamental step to reduce confounding factors. Additionally, targeting hypotheses helps diminish the likelihood of spurious correlations. It is recommended that Google Trends be leveraged as a complementary infoveillance tool by government agencies to monitor and predict vaccine adherence in this and future crises by following the methods proposed in this paper.
