An Exploration on Heterologous/Homologous Boosters and COVID-19 Using the BEEHIVE Study Population

With Novavax's new 2023-2024 protein subunit vaccine, our primary objective was to compare the COVID-19 frequency of a specific heterologous booster combination (mRNA primer/Novavax protein booster) from a homologous mRNA one using the BEEHIVE study population. Our analysis included 973 participants (374 for Novavax, 368 for Pfizer, and 231 for the control). The COVID Rapid Antigen Test (RAT) results were then categorized by booster type: heterologous (mRNA primer/Novavax booster) or homologous (mRNA only). Each booster group was stratified by the number of vaccinations a participant received prior to joining the BEEHIVE study (2, 3, 4, or ‚â•5 doses). Odds ratios and chi-squared tests were calculated with a 95% confidence interval. Results showed that receiving a vaccination in general was associated with lower odds of testing positive for COVID-19: odds ratio was 0.549 (95% CI, [0.363, 0.838]). However, the analysis comparing heterologous vs homologous boosters found no significant difference in RAT COVID-19 positivity, except in the group receiving 3 mRNA doses prior to enrollment: odds ratio was 2.985 (95% CI, [1.190, 8.215]). Thus, the results of our analysis remain largely inconclusive as we were unable to reject the null hypothesis for the rest of the dosage groups. It is possible our study was too underpowered to detect a significant difference in this subgroup analysis. Additionally, hybrid immunity could be a potential confounder, as it was statistically associated with RAT COVID-19 positivity (p-value: 0.044), and further research investigating this relationship is needed.