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.