Comparison of the Effectiveness and Safety of Heterologous Booster Doses with Homologous Booster Doses for SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis

Abstract

As vaccine resources were distributed unevenly worldwide, sometimes there might have been shortages or delays in vaccine supply; therefore, considering the use of heterogeneous booster doses for Coronavirus disease 2019 (COVID-19) might be an alternative strategy. Therefore, we aimed to review the data available to evaluate and compare the effectiveness and safety of heterologous booster doses with homologous booster doses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We searched relevant studies up to 27 April 2022. Random-effects inverse variance models were used to evaluate the vaccine effectiveness (VE) and its 95% confidence interval (CI) of COVID-19 outcomes and odds ratio (OR) and its CI of safety events. The Newcastle–Ottawa quality assessment scale and Cochrane Collaboration’s tool were used to assess the quality of the included cohort studies. A total of 23 studies involving 1,726,506 inoculation cases of homologous booster dose and 5,343,580 inoculation cases of heterologous booster dose was included. The VE of heterologous booster for the prevention of SARS-CoV-2 infection (VEheterologous = 96.10%, VEhomologous = 84.00%), symptomatic COVID-19 (VEheterologous = 56.80%, VEhomologous = 17.30%), and COVID-19-related hospital admissions (VEheterologous = 97.40%, VEhomologous = 93.20%) was higher than homologous booster. Compared with homologous booster group, there was a higher risk of fever (OR = 1.930, 95% CI, 1.199–3.107), myalgia (OR = 1.825, 95% CI, 1.079–3.089), and malaise or fatigue (OR = 1.745, 95% CI, 1.047–2.906) within 7 days after boosting, and a higher risk of malaise or fatigue (OR = 4.140, 95% CI, 1.729–9.916) within 28 days after boosting in heterologous booster group. Compared with homologous booster group, geometric mean neutralizing titers (GMTs) of neutralizing antibody for different SARS-CoV-2 variants and response rate of antibody and gama interferon were higher in heterologous booster group. Our findings suggested that both homologous and heterologous COVID-19 booster doses had great effectiveness, immunogenicity, and acceptable safety, and a heterologous booster dose was more effective, which would help make appropriate public health decisions and reduce public hesitancy in vaccination.

Heterologous boosting of neutralizing activity against Delta and Omicron SARS-CoV-2 variants in CoronaVac-primed adults; a randomized study with SCB-2019 vaccine

“…Heterologous boosting has been reported to be associated with higher rates of some systemic adverse events, notably fever, myalgia, malaise and fatigue [20], but we did not observe this in our study in which the only difference between homologous and heterologous groups was a small increase in the rate of transient, mild to moderate injection site pain in the heterologous group.…”

Effectiveness of full (booster) COVID-19 vaccination against severe outcomes and work absenteeism in hospitalized patients with COVID-19 during the Delta and Omicron waves in Greece

“…Second, the brand name of the last vaccine dose only was considered. Nonetheless, evidence from large studies support the use of heterologous vaccine schedules [20] , [35] , [36] . Third, the small number of cases admitted to the ICU, on invasive mechanical ventilation, and those that died stratified by time elapsed since the last vaccine dose (<compared to > the mean of 128.9 days) may account for not detecting statistical significance in adverse outcomes.…”

Timing of last COVID-19 vaccine dose and SARS-CoV-2 breakthrough infections in fully (boosted) vaccinated healthcare personnel

“…Lastly, we did not restrict our analysis to the 95% of HCP who have been vaccinated with the BNT 162b2 mRNA vaccine only. However, large population studies support the use of heterologous vaccine schedules [ 23 , 24 ].…”