Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis

Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received. Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria. Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization. COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

目前多种新型冠状病毒肺炎（COVID-19）疫苗被用作加强针。本系统综述与荟萃分析旨在依据疫苗类型、接种剂量、接种时机、受试者特征及既往基础免疫方案，评估新冠疫苗加强针的反应原性。本研究按照预设标准，在2020年1月1日至2023年1月1日期间，检索了MEDLINE、Embase、Web of Science及CENTRAL四个数据库中的随机对照试验。最终纳入28项研究，涉及4类共19种疫苗：病毒载体疫苗、灭活疫苗、信使核糖核酸（mRNA）疫苗及蛋白亚单位疫苗。由于BNT162b2疫苗（辉瑞-生物泰克（Pfizer-BioNTech））是被比对最多的疫苗，故将其设为对照。发热、乏力、头痛、注射部位疼痛、红肿及硬结是最常报告的主动监测不良事件。mRNA疫苗的反应原性最强，其次为病毒载体疫苗与蛋白亚单位疫苗，灭活疫苗的反应原性最弱。全剂量加强针的反应原性强于半剂量加强针。采用BNT162b2的异源加强针，其反应原性强于使用与基础免疫相同疫苗的加强针。新冠疫苗加强接种方案的反应原性特征存在显著差异，且取决于接种剂量与疫苗类型，这可为制定针对性接种建议及为特定人群提供接种选择提供依据。进一步规范不良事件报告标准，将有助于后续相关研究的开展。