Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study - The Lancet
Summary
Background
COVID-19 vaccines provide protection against symptomatic infection that might require medical attention and against severe outcomes; however, there is a paucity of evidence regarding the effectiveness of the BNT162b2 and CoronaVac vaccines and their booster regimens against asymptomatic or mild omicron infections in the community. We aimed to measure the effectiveness of BNT162b2 and CoronaVac vaccines against asymptomatic and symptomatic SARS-CoV-2 omicron infections, during a period of omicron BA.2 predominance in Hong Kong.
Methods
In this prospective cohort study in a population that was generally infection-naive before the large omicron BA.2 wave between January and late May, 2022, we established a public health surveillance platform to monitor the evolving activity of SARS-CoV-2 infections in the community. We recruited a cohort of individuals aged 5 years and older between March 1 and March 7, 2022, from the general population. Individuals were enrolled from all 18 districts of Hong Kong, according to a predefined age-stratified quota, primarily by random digit dialing (generating suitable eight-digit local telephone numbers by randomly picking sets of the first four digits from a sampling frame, and randomly generating the last four digits), and supplemented by our existing cohorts (which included cohorts for studying influenza vaccination from school-based vaccination programmes and cohorts for SARS-CoV-2 seroprevalence from the community), to ensure representativeness of the population in Hong Kong. Participants did weekly rapid antigen testing with a self-collected pooled nasal and throat swab, regardless of symptom and exposure status, from March 1 to April 15, 2022. Individuals reporting a history of SARS-CoV-2 infection confirmed by laboratory PCR testing before enrolment were excluded from the vaccine effectiveness analysis to avoid potential bias due to infection-induced immunity. The primary outcomes of the study were the incidence of SARS-CoV-2 infection, including asymptomatic and symptomatic infections, and the vaccine effectiveness of BNT162b2 and CoronaVac vaccines. The effectiveness of one, two, and three doses of vaccination was estimated with a Cox proportional hazards regression model with time-dependent covariates, allowing for changes in vaccination status over time, after adjustment for demographic factors and pre-existing medical conditions.
Findings
Of the 8636 individuals included in the analysis, 7233 (84%) received at least two doses of vaccine, 3993 (46%) received booster doses, and 903 (10%) reported SARS-CoV-2 infection. Among these infections 589 (65·2%) were symptomatic and 314 (34·8%) were asymptomatic at the time of testing. Statistically significant protection against asymptomatic and symptomatic SARS-CoV-2 omicron infection was found only for those who received a BNT162b2 or CoronaVac booster dose, with a vaccine effectiveness of 41·4% (23·2 to 55·2; p=0·0001) and 32·4% (9·0 to 49·8; p=0·0098), respectively. The vaccine effectiveness of BNT162b2 and CoronaVac boosters was further increased to 50·9% (95% CI 31·0–65·0; p<0·0001) and 41·6% (15·0–59·8; p=0·0049), respectively, for symptomatic omicron infections. A similar pattern of vaccine effectiveness (55·8%, 22·9–74·6; p=0·0040) was also conferred after receipt of a BNT162b2 booster by individuals who received a CoronaVac primary vaccination series.
Interpretation
Two doses of either vaccine did not provide significant protection against COVID-19 infection. However, receipt of a BNT162b2 booster or CoronaVac booster was associated with a significantly lower risk of omicron BA.2 infection and symptomatic infection. Our findings confirm the effectiveness of booster doses to protect against mild and asymptomatic infection.
Funding
Henry Fok Foundation and Hong Kong Health Bureau.
Introduction
With the current global predominance of the omicron variant of SARS-CoV-2, previous understanding of the effectiveness of different COVID-19 vaccines against the ancestral strain and earlier variants is no longer sufficient to inform the way forward during the evolving COVID-19 pandemic.
Effect of mRNA vaccine boosters against SARS-CoV-2 omicron infection in Qatar.
Literature has generally suggested that a primary series plus booster doses of mRNA vaccine shows modest to high effectiveness against severe COVID-19 outcomes, including hospitalisation, mechanical ventilation, and death,
Clinical severity of, and effectiveness of mRNA vaccines against, COVID-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study.
Severity of omicron variant of concern and effectiveness of vaccine boosters against symptomatic disease in Scotland (EAVE II): a national cohort study with nested test-negative design.
Severity of omicron variant of concern and effectiveness of vaccine boosters against symptomatic disease in Scotland (EAVE II): a national cohort study with nested test-negative design.
Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during omicron predominance.
However, evidence of the effectiveness of vaccines in preventing mild and asymptomatic infections, which have potential public health implications for seeding downstream secondary transmission, are generally lacking.
Research in contextEvidence before this studyWith the evolving omicron variants of SARS-CoV-2, previous understanding of the effectiveness of COVID-19 vaccines against the ancestral strain and earlier variants is becoming increasingly insufficient. Newer omicron-specific vaccine-effectiveness estimates are needed to inform the way forward, especially for individuals who present with asymptomatic infection, who might either have no symptoms or develop symptoms later (pre-symptomatic), because of the potential public health implications for seeding downstream secondary transmission. We searched PubMed and MedRxiv, with no language restrictions, from database inception up to Sept 14, 2022, using the search terms “((vaccine effectiveness) AND (omicron)) AND (((BNT162b2) OR (Comirnaty)) OR (CoronaVac))”, and found 133 published articles and 791 preprints. 118 of these publications reported vaccine effectiveness against omicron outcomes, with 100 studies focused only on symptomatic infection or severe complications. Among the 18 studies that attempted to examine asymptomatic infections, only ten reported aggregated vaccine effectiveness rather than the vaccine effectiveness of specific vaccine types, three used only a risk-based testing approach, which was not optimal in ascertaining asymptomatic infections, and five were of restricted generalisability, as they focused on specific population subgroups (one each on haemodialysis patients, people who were incarcerated, and university students and employees, and two on children). To our knowledge, to date, no study has reported the vaccine effectiveness of the BNT162b2 booster or CoronaVac vaccines and booster regimens against omicron BA.2 asymptomatic infection.Added value of this studyThe population of Hong Kong was generally omicron-infection-naive before a large BA.2 wave extending from January 1 to April 30, 2022, and peaking in early March. Our prospective observational cohort study examined and compared the vaccine effectiveness of BNT162b2 and CoronaVac against asymptomatic and symptomatic SARS-CoV-2 omicron BA.2 infections. The systematic use of weekly SARS-CoV-2 rapid antigen testing for outcome ascertainment, regardless of exposure status and symptoms, allowed for identification of asymptomatic infections, including in those who remained asymptomatic and those who went on to develop symptoms (pre-symptomatic), and improved generalisability to community infections. To our knowledge, our study is the first to report the effectiveness of CoronaVac vaccines against SARS-CoV-2 omicron BA.2 asymptomatic infections. Our results suggest that no significant protection was observed for one or two doses of BNT162b2 and CoronaVac. Significant protection against SARS-CoV-2 asymptomatic and symptomatic omicron infection was shown for those who received a BNT162b2 booster or CoronaVac booster. A similar pattern of vaccine effectiveness was also conferred by administering a BNT162b2 booster dose to individuals who received a CoronaVac primary vaccination series.Implications of all the available evidenceOur results suggest that a booster dose of COVID-19 vaccine is needed to achieve significant protection against omicron infection, by either an inactivated or mRNA vaccine, which highlights the importance of achieving high coverage of booster doses. Our study shows the experimental feasibility for examining vaccine effectiveness against asymptomatic and mild infections using a systematic outcome-ascertainment approach, irrespective of exposures status and symptoms.
However, examination of the effectiveness of vaccines in preventing mild and asymptomatic COVID-19 infections is inherently challenging. Common study designs used for studying vaccine effectiveness, including test-negative design, depend on symptomatic cases presenting in various settings.
Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during omicron predominance.
Therefore, such designs can be biased towards the more severe end of the clinical spectrum and might not be generalisable to all cases in the community. Moreover, previous observational vaccine effectiveness studies that do not have a prescribed similar testing schedule might be biased by the potential differential testing frequencies and behaviours among people with different vaccination status.
Testing behaviour may bias observational studies of vaccine effectiveness.
Previous vaccine effectiveness studies against omicron infections have focused mainly on various mRNA vaccine candidates, including BNT162b2 (Pfizer–BioNTech) and the mRNA-1273 (Moderna) vaccine, or adenoviral vector vaccines, such as ChAdOx1 nCoV-19 (AstraZeneca),
Severity of omicron variant of concern and effectiveness of vaccine boosters against symptomatic disease in Scotland (EAVE II): a national cohort study with nested test-negative design.
Effectiveness of BNT162b2 vaccine against omicron in children 5 to 11 years of age.
and, to our knowledge, the effectiveness of inactivated vaccine (eg CoronaVac [Sinovac]) against omicron infections has yet to be investigated. Although previous studies have reported the effectiveness of BNT162b2 among children and adolescents,
Effectiveness of BNT162b2 vaccine against omicron in children 5 to 11 years of age.
the comparative effectiveness of BNT162b2 and CoronaVac vaccines among different age groups remains unclear. We did a study examining the effectiveness of BNT162b2 and CoronaVac vaccines against SARS-CoV-2 infection, using a prospective and systematic approach to outcome ascertainment, regardless of risk or symptoms, and therefore capturing mild and asymptomatic infections, during a period of omicron BA.2 predominance in Hong Kong.
Results
1560 (15·3%) of 10 196 individuals in the cohort had reported themselves to be previously infected with SARS-CoV-2 before enrolment and thus were excluded from the vaccine effectiveness analysis. Among the 8636 individuals included in the vaccine effectiveness analysis, 903 (10·5%) were infected during the surveillance period, with a median of 10 days (IQR 6–17) between enrolment and infection; among these infections 589 (65·2%) were symptomatic and 314 (34·8%) were asymptomatic. 7233 (84%) individuals had received at least two doses of vaccine and 3993 (46%) received booster doses. The distribution of positive and negative cases according to sex, age, and comorbidity status was similar (table 1). Sociodemographic factors associated with test positivity included household size, district, housing type, and TPU level median monthly domestic household rent (appendix p 2). High compliance with weekly testing was maintained in 8419 (97·5%) individuals, with a similar pattern across different characteristics (appendix p 3).
Table 1Characteristics of people tested for SARS-CoV-2 with rapid antigen test, according to test positivity or negativity
Data are n (%) or n/N (%), unless otherwise indicated. Only individuals aged 5 years and older were included.
764 (8·8%) of 8636 individuals were unvaccinated, 639 (7·4%) had only one dose of vaccine, 3240 (37·5%) had two doses, and 3993 (46·2%) had three doses (table 1). Differences in monthly domestic household rent, housing type, and geographical district were observed between vaccination status; in particular, individuals who received three doses of vaccine had a higher likelihood of being male, older, having a chronic illness, having a smaller household size, and being asymptomatic (appendix p 4). 2308 (71·2%) of 3240 individuals who received two doses of vaccine had received the second dose more than 3 months before testing, so vaccine effectiveness was stratified by those who had completed the second dose within 3 months or 3 months or longer before testing. For the primary series of two vaccine doses, 2353 (27·2%) of 8636 individuals received BNT162b2 and 875 (10·1%) individuals received CoronaVac. For the primary series using BNT162b2, 1884 (21·8%) of 8636 individuals completed the two doses 3 months before testing and 469 (5·4%) completed the two doses within 3 months of testing (table 2). For the primary series using CoronaVac, 458 (5·3%) of 8636 individuals completed the two doses 3 months before testing and 417 (4·8%) completed the two doses within 3 months of testing (table 2). As switching of vaccine between the two doses was not allowed in the primary series, only 12 (0·1%) of 8636 individuals had two doses with other vaccine combinations, and were not included in the primary analysis (table 2).
Table 2Vaccination status by age group
Data are n (%), unless otherwise indicated.
For individuals who received three doses of vaccine, 2432 (28·2%) of 8636 received three doses of BNT162b2 and 1050 (12·2%) received CoronaVac. A small proportion of individuals received a combination, either of a primary series of CoronaVac followed by a BNT162b2 booster (463 [5·4%] of 8636 individuals), or a primary series of BNT162b2 followed by a CoronaVac booster (29 [0·3%] individuals). 19 (0·2%) of 8636 individuals received three vaccine doses in other combinations and were not included in the analysis (table 2).
Among the 886 participants aged 5–17 years, 323 (36·5%) received two doses of vaccine and 287 (32·4%) received one dose of vaccine. As only 60 (6·8%) of 886 individuals aged 5–17 years had received three doses of vaccination, the effectiveness of booster vaccination was not examined in this age group. Among the 6014 individuals aged 18–59 years, 2988 (49·7%) received three doses of vaccine and 2404 (40·0%) received two doses of vaccine. Among the 1736 individuals aged 60 years and older, 945 (54·4%) received three doses of vaccine and 513 (29·6%) received two doses of vaccine. The observed differential distribution of vaccination status by age group was largely consistent with the territory-wide figures of vaccine coverage for the population in Hong Kong (table 2).
Table 3 shows the differential risk of SARS-CoV-2 infection stratified according to vaccination status. The lowest positivity rate was observed among individuals who received three doses (5·4%, 95% CI 4·8–6·2), followed by those who received two doses within 3 months (6·8%, 5·3–8·6). Higher positivity rates were observed among individuals who received only one dose (14·7%, 12·2–17·7) or two doses at least 3 months previously (17·6%, 16·1–19·2). Detailed vaccination status by age group is shown in the appendix were shown in the appendix (pp 5–7). For all age groups, the positivity rate was lower for individuals with a more recent primary series of vaccination within 3 months compared with those who completed vaccination at least 3 months ago.
Table 3Vaccination status and risk of infection
Data are n (%), unless otherwise indicated.
A potential attenuation of infection severity was shown in those who received a booster BNT162b2 dose compared with unvaccinated individuals, both in terms of a lower number of symptoms (6·21, SD 3·64 vs 8·09, 4·13; p=0·0040) and a lower mean severity score was found (8·35, 6·31 vs 11·56, 7·93; p=0·0068). No impact on symptom profile was observed for those who received two doses or fewer of BNT162b2 (appendix p 8).
Using unvaccinated people as the reference group in the multivariate model, the first dose of BNT162b2 vaccine provided a vaccine effectiveness of 16·5% (95% CI –19·5 to 41·6; p=0·32) against asymptomatic and symptomatic SARS-CoV-2 omicron infection (table 4). Vaccine effectiveness after two doses (ie, primary series) was not significant (27·6%, –6·3 to 50·7; p=0·10) within 3 months, and point estimates declined to a very low level of 1·1% (–22·4 to 20·1; p=0·92) at 3 months and beyond. A BNT162b2 booster vaccine improved the effectiveness to 41·4% (23·2 to 55·2; p=0·0001; figure; table 4).
Table 4Effectiveness of the BNT162b2 and CoronaVac vaccines against COVID-19 omicron BA.2 infection
Data are n, unless otherwise indicated. Data were adjusted for age group, gender, chronic illness, household size, district, housing type, Hong Kong tertiary planning unit level, and monthly household rent. Symptomatic infections were defined as those with a positive rapid antigen test result after an individuals reported at least one of 19 surveyed symptoms.
FigureCumulative risk of infection with the SARS-CoV-2 omicron variant according to vaccination status in asymptomatic and symptomatic infection (A) and symptomatic infection only (B)
A similar pattern of vaccine effectiveness for any SARS-CoV-2 infection, but with a slightly lower magnitude of protection, was given by the CoronaVac vaccine. The first dose of CoronaVac provided a vaccine effectiveness of –1·6% (95% CI –30·8 to 26·2; p=0·92) against asymptomatic and symptomatic SARS-CoV-2 omicron infection (table 4). Vaccine effectiveness after two doses was not significant within 3 months (5·4%, –25·6 to 28·8; p=0·70) or at 3 months and beyond (22·7%, –15·2 to 48·2; p=0·21). A CoronaVac booster improved the vaccine effectiveness to 32·4% (9·0 to 49·8; p=0·0098; figure; table 4). A similar amount of protection was observed for CoronaVac and BNT162b2, with non-significant relative vaccine effectiveness (appendix p 13).
The vaccine effectiveness against any infection of a booster dose using a switched vaccine type was also examined. For people who received a primary series of CoronaVac, the vaccine effectiveness for a booster dose using BNT162b2 was 31·3% (95% CI –1·0 to 53·3; p=0·056), similar to the values for a booster with the same vaccine (table 4). No significant difference in vaccine effectiveness was found in the estimation of relative effectiveness for the types of booster dose (p=0·86; appendix p 13). The effectiveness of a CoronaVac booster after a primary series of BNT162b2 was not examined because of the small sample size.
For vaccine effectiveness against symptomatic SARS-CoV-2 omicron infection, a booster dose generally showed a similar pattern of effectiveness but conferred a higher level of protection, with vaccine effectiveness of 50·9% (95% CI 31·0–65·0; ptable 4). A BNT162b2 booster for those who received a primary series of CoronaVac also conferred a similar significant vaccine effectiveness of 55·8% (22·9–74·6; p=0·0040) against symptomatic infection (table 4). The relative vaccine effectiveness against symptomatic infection between CoronaVac and BNT162b2 was not significant (appendix p 13).
To address the potential confounding effect of differential vaccine coverage in subpopulations, the age-specific effectiveness of different vaccine types was further examined. For all SARS-CoV-2 omicron infections, a similar non-significant protection of the first dose and primary series within 3 months was observed across all age groups (appendix pp 17, 20, 23). For adults aged 18–59 years, we observed no significant protection for the first dose of BNT162b2 (20·4%, 95% CI –30·9 to 51·6; p=0·37), first dose CoronaVac (–0·6%, –72·2 to 41·3; p=0·98), two BNT162b2 doses within 3 months (35·3%, –4·2 to 59·8; p=0·073), two CoronaVac doses within 3 months (38·2%, –19·5 to 68·0; p=0·15), or a second dose received beyond 3 months (2·5, –29·0 to 26·2; p=0·86 for BNT162b2 and –3·0, –45·9 to 27·3; p=0·87) for CoronaVac; appendix p 17). Significant protection was only observed for those who received a BNT162b2 booster vaccine, with a vaccine effectiveness of 42·1% (19·5 to 58·4; p=0·0012; appendix p 17). For symptomatic SARS-CoV-2 omicron infection, the significant protection of a BNT162b2 booster was also maintained, with a slightly higher vaccine effectiveness of 51·6% (27·7 to 67·6; p=0·0004) for those receiving a BNT162b2 primary series and 60·0% (20·8 to 79·8; p=0·0085) for those receiving a CoronaVac primary series.
For adults aged 60 years and older, no significant protection against SARS-CoV-2 omicron infection was shown after either one dose of BNT162b2 (–69·7%, 95% CI –353·1 to 36·5; p=0·29), one dose of CoronaVac (–65·0%, –219·6 to 14·8; p=0·14), two BNT162b2 doses within 3 months (–39·3%, –236·4 to 42·4; p=0·46), or two CoronaVac doses within 3 months (–65·7%, –228·5 to 16·5; p=0·15; appendix p 20). A booster vaccine of either BNT162b2 or CoronaVac did not provide significant protection against SARS-CoV-2 omicron infection for this older population, with a vaccine effectiveness of –1·5% (–101·0 to 48·7; p=0·97) and 25·2% (–56·0 to 64·1; p=0·44), respectively (appendix p 20). A similarly negligible protection for older people was observed for symptomatic omicron infection (appendix p 20).
For individuals aged 5–17 years, no significant protection against SARS-CoV-2 omicron infection was shown after one dose of BNT162b2 (32·4%, 95% CI –29·0 to 64·6; p=0·24), one dose of CoronaVac (22·7%, –38·3 to 56·8; p=0·39), two BNT162b2 doses within 3 months (3·2%, –220·7 to 70·8; p=0·96), or two CoronaVac doses within 3 months (55·6%, –50·3 to 86·9; p=0·19; appendix p 23). A similarly negligible protection for this population was observed for symptomatic omicron infection (appendix p 23). The age-specific protection conferred by either a BNT162b2 or CoronaVac booster after a primary series was not examined for those aged 5–17 years because of the small sample size.
Discussion
This prospective cohort study adopted a comprehensive non-symptom and risk-based outcome-ascertainment approach by regular rapid antigen testing to evaluate the vaccine effectiveness of the primary series and booster dose of vaccination against SARS-CoV-2 during omicron BA.2 predominance. A representative cohort that covered different population subgroups by age, gender, monthly income, and district was recruited to increase the generalisability of our findings, and stratified analysis provided an age-specific and vaccine-type-specific estimate for different vaccination statuses. Our surveillance initiative, with regular testing regardless of symptom status or exposure history, allowed assessment of vaccine effectiveness against both symptomatic and asymptomatic infection. The provision of free rapid antigen tests to all enrolled participants helped to minimise the potential effect of changing testing policy and capacity on outcome ascertainment. The exclusion of 15·3% of individuals who were previously infected was consistent with the reported local seroprevalence against BA.2 of 7·3% before the fifth wave of SARS-CoV-2 in November to December, 2021,
SARS-CoV-2 IgG seropositivity after the severe omicron wave of COVID-19 in Hong Kong.
and might have helped us avoid wrongly attributing protection to previous infection in the vaccine effectiveness analysis. Understanding the updated effectiveness of available vaccines against infection, including asymptomatic infection, in relation to the evolving omicron variants is essential for guiding vaccination policies and informing future vaccine development.
Our findings showed that a booster dose of vaccination conferred substantial protection against SARS-CoV-2 infection by the omicron variant, including mild and asymptomatic cases. Significant protection against infection was observed only for three doses of vaccine. This finding supports the need for a booster dose for protection against the omicron variant, and fits with the current recommendation for booster doses in Hong Kong,
US Centers for Disease Control and Prevention
Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States.
We also observed differential vaccine effectiveness for the booster dose for different age groups. Specifically, moderate and statistically significant protection from a BNT162b2 booster dose was only achieved in those aged 18–59 years, whereas no significant protection was conferred in those aged 60 years and older, which is compatible with the general finding of a lower vaccine effectiveness for older individuals in the literature.
Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of COVID-19 in Brazil: test negative case-control study.
This differential vaccine effectiveness highlights the need to explore the potential feasibility and benefit of more targeted vaccination regimens for optimising protection of different subpopulations in the community.
For the primary series of two doses of either BNT162b2 or CoronaVac completed within 3 months or at least 3 months ago, our results showed no significant protection was achieved in all age groups. Compared with a previous study on symptomatic omicron infection, our finding of no significant protection from the primary series of BNT162b2 contrasted with that study's finding of high vaccine effectiveness (65·5%, 95% CI 63·9–67·0) assessed at 4 weeks,
Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant.
Although a BNT162b2 primary series completed within 3 months did not show significant vaccine effectiveness, the higher vaccine effectiveness compared with a course completed 3 or more months ago (27·6% vs 1·1%) was compatible with the rapid waning of effectiveness reported in previous studies.
Duration of effectiveness of vaccination against COVID-19 caused by the omicron variant.
This observed difference might also have been partly due to our adjustment for immortal time bias to avoid potential wrongful attribution of protective effects to a more recent vaccination event.
Our findings showed that significant vaccine effectiveness against symptomatic or asymptomatic omicron infection was conferred by a third dose of either BNT162b2 or CoronaVac. The protection conferred by a BNT162b2 or CoronaVac booster was further increased when considering only symptomatic omicron infections. Our results were generally much lower than previously reported vaccine effectiveness of booster doses against the more severe outcomes of omicron infection, including an effectiveness of 86% against hospital admission
Clinical severity of, and effectiveness of mRNA vaccines against, COVID-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study.
and more than 90% effectiveness against severe disease or death,
Effectiveness of mRNA vaccination in preventing COVID-19-associated invasive mechanical ventilation and death—United States, March 2021–January 2022.
but were consistent with the vaccine effectiveness of 52·2% (95% CI 48·1–55·9) of three doses of BNT162b2 against symptomatic omicron BA.2 infection reported in Qatar, where universal testing allowed detection of cases of all severities.
Effects of previous infection and vaccination on symptomatic omicron infections.
Although our results were lower than the reported vaccine effectiveness in a previous study (70·2–73·5% for BNT162b2 and 32·4–51·0 % for CoronaVac) of patients with mild or moderate COVID-19 who were admitted to hospital during the same epidemic wave in Hong Kong using an ecological study design,
Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study.
our study might capture the milder end of the spectrum of infection in the community, with most individuals not requiring medical attention. With this understanding, our findings are consistent with the overall picture of a rapidly attenuating vaccine effectiveness effect size when the examined outcomes were shifted from the more severe to the milder end of the clinical spectrum in the published literature.
Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, delta or omicron SARS-CoV-2.
our study design with regular scheduled testing might help to avoid potential differential outcome ascertainment related to the duration of viral shedding, reducing the likelihood of detecting an infection among vaccinated people, and the resultant bias towards an overestimation of the vaccine effectiveness effect size.
Despite the low level of protection against infections with mild or no symptoms, the high proportion of mild infections might still impose a non-trivial collective clinical burden in the community during a rapid surge of an evolving epidemic, as in the fifth SARS-CoV-2 wave in Hong Kong. However, the high proportion of asymptomatic cases that might have been prevented by booster vaccination, which otherwise might have potentially seeded downstream secondary transmission, might help to prevent further propagation of the epidemic in the community due to the shedding of virus in the absence of awareness, appropriate management, isolation, or quarantine measures. This potential public health implication might become even more important as newer SARS-CoV-2 variants with higher transmissibility and milder clinical symptoms emerge,
Secondary attack rate, transmission and incubation periods, and serial interval of SARS-CoV-2 omicron variant, Spain.
Besides the indirect effect on transmission through preventing the incidence of infection, transmission might also be prevented through reduced transmissibility of infection in breakthrough cases in vaccinated people. Although current literature generally regards the vaccine effectiveness of two doses for preventing omicron transmission to be minimal,
Infectiousness of SARS-CoV-2 breakthrough infections and reinfections during the Omicron wave.
some studies have reported modest effectiveness of a booster dose for reducing secondary transmission related to breakthrough cases in vaccinated people in households or institutional settings,
Transmission of SARS-CoV-2 omicron VOC subvariants BA.1 and BA.2: evidence from Danish households.
signifying the value and implications of the vaccine even if effectiveness against mild infection is not high. Although our study did not directly examine the outcome of transmission or viral shedding, our data did reveal a potential attenuation of infection severity in those who received a booster BNT162b2 vaccine compared with unvaccinated individuals, both in terms of a lower number of symptoms and a lower mean severity score. However, similar to the existing literature, no effect on symptom profile was observed for those who received two doses or fewer of vaccine.
The similar magnitude of vaccine effectiveness of the mRNA vaccine (BNT162b2) and inactivated vaccine (CoronaVac) implies that both vaccine types are effective against omicron infection. The similar protection achieved with either the same or different booster regimens also supports the current recommendation of BNT162b2 boosters in Hong Kong and some other countries,
European Medicines Agency
EMA and ECDC recommendations on heterologous vaccination courses against COVID-19: ‘mix-and-match’ approach can be used for both initial courses and boosters.
which might give the advantage of facilitating higher booster dose uptake, with the enhanced autonomy of personal preference, and lead to less issues with vaccine availability during an evolving pandemic.
This surveillance initiative is an observational study with some possible biases and should be interpreted with caution. As a history of previous PCR-confirmed infection was ascertained by self-reporting, some under-ascertainment of previous infection might have been present and affected our vaccine effectiveness estimation. However, given the straightforward and official nature of the case definition, and the lack of obvious benefit for untruthful reporting, substantial inaccurate recall might be unlikely. Government mandatory testing orders in relation to community exposure risk, which were instituted independent of vaccination status, might serve to capture some people with no symptoms and to prevent substantial differential under-ascertainment among people with different vaccination statuses.
Imperfect performance in terms of suboptimal sensitivity and specificity of rapid antigen testing might cause misclassification of infection status,
US Food and Drug Administration
INDICAID COVID-19 rapid antigen at-home test.
as in our study, would thus be an important step to minimise potential bias in vaccine effectiveness estimation.
The availability of rapid antigen testing kits for regular self-testing, irrespective of symptom status or exposure risk, should facilitate early identification of both symptomatic and asymptomatic cases.
Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening.
However, case counting on the basis of PCR testing or voluntary rapid antigen test result reporting might underestimate the risk of infection and case ascertainment, as testing can be affected by any change in testing policy, health seeking behaviour, laboratory testing capacity, or incomplete reporting practices due to the fear of isolation or quarantine order being imposed.
As the changing symptom pattern after rapid antigen test positivity was not continuously monitored in our surveillance platform, classification as either symptomatic or asymptomatic in the current study was based primarily on the data at the time of the positive rapid antigen test. As some people who were asymptomatic on original testing might develop symptoms later (ie, pre-symptomatic), this strategy might affect precise estimation of the vaccine effectiveness against symptomatic infection; however, this should have no effect on the estimation of vaccine effectiveness against both symptomatic and asymptomatic infection.
Although behavioural factors, such as wearing a mask and physical distancing, might affect infection risk and be potential residual confounders in this study, a substantial difference between vaccinated and unvaccinated participants, or between individuals who received two doses of vaccine and those who received three doses, was not expected, as universal mask wearing and stringent social distancing requirements were legally required for the whole community during the study period in Hong Kong, irrespective of vaccination.
The Government of the Hong Kong Special Administrative Region
Prevention and control of disease ordinance (cap 599).
Another limitation was our inability to estimate vaccine effectiveness for some subgroups, due to the relatively small number of individuals who received some vaccine regimens. As the local population had recently started to receive booster doses, and booster doses had only recently been approved for children, the additional protection achievable by a booster dose in children, and the waning effectiveness of booster doses over time, were not evaluated. A further study examining the effect of booster doses on younger age groups and the waning effectiveness of booster doses is warranted, to inform the assessment of and optimise vaccine policy in the evolving pandemic.
In conclusion, we assessed the vaccine effectiveness of the BNT162b2 and CoronaVac vaccines in different regimens and age groups and found that a BNT162b2 or CoronaVac booster dose achieved significant protection against omicron infection in Hong Kong. These updated vaccine effectiveness estimates allow assessment of the public health impact of COVID-19 vaccines for preventing transmission of symptomatic and asymptomatic infections in the community. We found similar effectiveness for both vaccine types, and a potential association of effectiveness with age. Our findings support the use of different booster vaccination regimens from the primary series during the evolving pandemic.
GML and DKMI conceived and designed the study. NNYT and HCS collected the data. NNYT and DKMI accessed and verified the data. BJC advised on the statistical analysis. NNYT did the statistical analysis. NNYT and DKMI interpreted the data. NNYT and DKMI wrote the first draft of the manuscript, and all authors provided critical review and revision of the text and approved the final version for publication. All authors had full access to all the data in the study and accept final responsibility for the decision to submit for publication.
Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study - The Lancet Read More
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