DISCUSSION
In this case-control study conducted from 4 April 2022 to 20 April 2022 in Lu’an City, we examined the real-world effectiveness of COVID-19 vaccines against the Omicron BA.2 variant among the population. In total, the overall VE against the Omicron variant infection was 35.0% (95% CI: −9.1–61.3%) for any COVID-19 vaccine. We did find significant differences in protection against Omicron variant infection when comparing three types of COVID-19 vaccines (inactivated vaccines, a recombinant protein vaccine, and an Ad5-nCoV vaccine), and the overall VE of the Ad5-nCoV vaccine was 65.8% (95% CI: 12.8–86.6%), which was the highest of included the three types of vaccines. Heterologous booster vaccination (VE = 76.4%, 95% CI: 14.3–93.5%) offered more protection than homologous booster vaccination (VE = 51.8%, 95% CI: 9.6–74.3%).
Cases included symptomatic or asymptomatic patients, and asymptomatic cases were 57.7% of all cases. A growing number of reports indicated that the Omicron-associated COVID-19 disease was less severe than the Delta-associated COVID-19 disease, resulting in more asymptomatic patients[30,31]. A study from India showed that the majority of patients infected with Omicron were asymptomatic (56.7%)[32], consistent with our study. The Faroe Islands study reported that in over half the cases, patients assessed their illness as asymptomatic or mild[33]. Infected patients showing no or mild symptoms indicates that the Omicron variant has increased immune escape ability, making it difficult to prevent. Among all cases, fever (43.4%), cough (37.7%), pharyngitis (25.7%), and rhinitis (12%) were the most prevalent symptoms, which was consistent with a study conducted in India which revealed that the predominant symptoms reported included fever (43.2%), and the rest of the infected patients had milder symptoms[34]. In this study, we found that COVID-19 vaccines offered 46.8% (95% CI: 9.5–68.7%) protection from infection within 6 months. In contrast, no protection was provided after 6 months. One study from Qatar showed that the effectiveness of the last dose of vaccination persisted at an approximately relatively high level for about 6 months, then it dramatically declined after 6 months[35]. Another study from Mexico showed that the VE against illness declined from 48% after 14–60 days following full vaccination to 20% after 61–120 days[36]. The median months since the last dose of vaccination in the case group (6.8, 3.0–8.0) was longer than in the control group (3.8, 2.9–7.5), indicating that the VE of COVID-19 vaccines had declined in the case group. These findings highlighted the importance of booster vaccination in persons >6 months after the full vaccination.
Vaccination status was statistically different between the cases and control groups (P = 0.006), and there were more unvaccinated individuals in the case group compared to the control group. Our results revealed that the overall protection of partial and full vaccination was negligible but showed 51.6% (95% CI: 15.2–72.4%) in the booster vaccination group, with the same results for each type of COVID-19 vaccine. The results were in line with previous studies. A study conducted in Hong Kong found statistically significant protection against the Omicron variant among individuals who received three doses of a COVID-19-inactivated vaccine, and the adjusted VE was 52%[37]. A previous study in Hong Kong estimated that the third-dose vaccine effectiveness for CoronaVac against BA.2 was 51.0%[38]. Similar results were reported from England, Italy, Hong Kong, Japan, and Israel[37,39-42]. Unexpectedly low effectiveness against Omicron in enhanced vaccinated individuals could reflect the gradual waning of vaccine protection, strongly suggesting that booster shots for eligible people, on schedule, are critically necessary. Our study design was consistent with previous real-world vaccine effectiveness studies and expanded upon their findings as most of the other studies only assessed the VEs of inactivated vaccines and Ad5-nCoV vaccines, while we also considered a recombinant protein vaccine. Three doses of inactivated vaccines provided 48.0% (95% CI: 8.0–70.6%) protection in our study. One study from Shanghai showed that inactivated vaccines were 16.3% effective overall against Omicron variant infection[22]. Considering the large number of people who had been infected in that outbreak in Shanghai, the risk of population exposure was greatly increased. Surprisingly, the Ad5-nCoV vaccine showed the highest VE among the three types of vaccines in booster vaccination (VE = 62.9%, 95%CI: 1.8–86%). The Ad5-nCoV vaccine is a replication-defective vaccine that expresses the spike glycoprotein of SARS-CoV-2, which induced significant immune responses after a single vaccination with 5 × 1010 viral particles[43,44]. Nevertheless, only 3.9% of all subjects had received the Ad5-nCoV vaccine because of the low supply of the Ad5-nCoV vaccine in Lu’an City, and further observations are needed. The recombinant protein vaccine (ZF2001) has received conditional marketing authorization in China and was only used in several provinces of China at the beginning of its launch[45]. Frustratingly, our findings indicated that the adjusted VE of the recombinant protein vaccine (12.1%, 95%CI: −78.6–56.8%) was the lowest of the three types of vaccines. In our study, 99.4% of individuals vaccinated with the recombinant protein vaccine had received the last dose of vaccination more than 6 months prior to last exposure, both in the cases and control groups, and none of them received a booster dose due to Chinese immunization strategies. Given the above, the VE of the recombinant protein vaccine decreased precipitously, and boosters are urgently needed for those who have already received three doses of the recombinant protein vaccine.
Our findings showed that the adjusted VE of heterologous booster vaccination (76.4%, 95% CI: 14.3–93.5%) was considerably higher than that of homologous booster vaccination (51.8%, 95% CI: 9.6–74.3%). Jin, et al.[43]reported that heterologous booster vaccination seemed to be more effective in minimizing the negative effect of the response to the vectors. Similarly, the results of a clinical trial conducted in China suggested that heterologous booster vaccination with the Ad5-nCoV vaccine was safe and more immunogenic than homologous booster vaccination[46]. Promisingly, the results of previous clinical studies revealed that the incidence of adverse reactions in the heterologous booster vaccination group was significantly less than in the homologous booster vaccination group[47]. Pain and fever were the most frequently reported injection site adverse reactions and systemic adverse reactions, respectively, and none of the serious adverse events were related to vaccination[48]. As heterologous booster vaccination was implemented for the population shortly before the outbreak in Lu’an, only 24 individuals (1.9%) had completed heterologous booster vaccination in this study. Despite this, heterologous booster vaccination provided significantly better protection than homologous booster vaccination.