Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

在中国境内以SARS-CoV-2奥密克戎变异株为主导的全国性疫情期间，采用腺病毒载体5型（Ad5）新冠疫苗实施异源加强免疫的有效性，在大型多元人群中尚未见公开报道。本研究在中国六个省份开展了一项大型队列对照研究，并针对此次疫情期间的新冠病毒感染发病风险开展回顾性调查。本研究纳入既往五项临床试验中年龄≥18岁、已完成1至3剂次灭活新冠疫苗（Inactivated COVID-19 Vaccine, ICV）基础免疫，随后接受肌内注射或经口吸入型Ad5载体新冠疫苗作为异源加强免疫的受试者，组建异源试验队列。我们以1:4的比例进行倾向性得分匹配，将异源试验队列中的受试者与完成3剂次ICV基础免疫的社区人群（ICV社区队列）进行个体匹配作为对照。2023年2月4日至4月10日期间，55710名受试者中有41504名（74.5%）完成了本次调查。从末次疫苗接种至新冠症状发作的中位时间为303.0天（四分位间距293.0~322.0天）。异源试验队列的新冠感染率为55.8%，而ICV社区队列的感染率为64.6%，据此计算得到相对保护效力为13.7%（95%置信区间11.9~15.3）。此外，该疫苗针对新冠相关门诊就诊及住院治疗的相对保护效力更高，分别为25.1%（95%置信区间18.9~30.9）与48.9%（95%置信区间27.0~64.2）。研究结果显示，在接种加强免疫后10个月时，与采用ICV的同源3剂次免疫方案相比，Ad5载体新冠疫苗异源加强免疫仍可对新冠突破性感染提供一定的额外保护作用。