Assessment of Heterologous and Homologous Boosting With Inactivated COVID-19 Vaccine at 3 Months Compared With Homologous Boosting of BNT162b2 at 6 Months

IMPORTANCE Evidence for the timing of booster vaccination after completion of BNT162b2 and CoronaVac primary vaccination is crucial to guide policy recommendations. OBJECTIVE To compare the odds of symptomatic SARS-CoV-2 infection and COVID-19-related outcomes after heterologous and homologous boosting of CoronaVac at 3-month intervals and homologous boosting of BNT162b2 at 6-month intervals, with BNT162b2 primary series (2 doses) as the reference group. DESIGN, SETTING, AND PARTICIPANTS This population-based retrospective cohort study used national data for Malaysia. Participants included all individuals aged 18 years and older who received a complete primary series of CoronaVac or BNT162b2 vaccine and were eligible for a booster dose between November 21, 2021, and December 28, 2021. Data were analyzed from November 21, 2021, to January 7, 2022. EXPOSURES Receipt of a booster vs no booster and categorized into primary series BNT162b2 (2 doses of BNT162b2), primary series CoronaVac (2 doses of CoronaVac), 3 doses of BNT162b2, primary series CoronaVac plus a BNT162b2 booster, and 3 doses of CoronaVac. MAIN OUTCOMES AND MEASURES The primary outcome was symptomatic SARS-CoV-2 infection. The secondary outcomes were COVID-19-related intensive care unit admission and death. All outcomes were observed from the day an individual was considered fully boosted (>= 14 days after booster dose). RESULTS Our cohort included 13 840 240 individuals (mean [SD] age, 39.9 [15.5] years; 7 040 298 [50.9%] men; 4 451 180 individuals [32.2%] with >= 1 comorbidities), of whom 5 081 641 individuals (36.7%) had received a booster dose. Using the primary series BNT162b2 recipients as reference, the adjusted odds against symptomatic SAR-CoV-2 infection were lower for individuals who received the primary series CoronaVac plus a BNT162b2 (adjusted odds ratio [aOR], 0.06 [95% CI, 0.05-0.06]), 3 doses of CoronaVac (aOR, 0.08 [95% CI, 0.06-0.10]), or 3 doses of BNT162b2 (aOR, 0.01 [95% CI, 0.00-0.01]). Receipt of heterologous booster (primary series of CoronaVac plus a BNT162b2 booster) was associated with lower odds of SARS-CoV-2 infection (aOR, 0.17 [95% CI, 0.17-0.18]) compared with homologous booster (3 doses of CoronaVac) for individuals aged 60 years and older (aOR, 0.19 [95% CI, 0.19-0.20]). CONCLUSIONS AND RELEVANCE In this cohort study, for individuals who received the CoronaVac primary series and a booster dose of BNT162b2 or CoronaVac at 3 months, the observed odds of symptomatic SARS-CoV-2 infection were similar to individuals who received the BNT162b2 primary series plus a third dose of BNT162b2 at 6 months. Heterologous booster is recommended for individuals aged 60 years or older who received the CoronaVac primary series, given the lower observed odds against symptomatic SARS-CoV-2 infection among those who received a BNT1612b2 booster.