The Lancet Regional Health - Western Pacific

BackgroundHong Kong, has operated under a zero-Covid policy in the past few years. As a result, population immunity from natural infections has been low. The fifth wave in Hong Kong, caused by the Omicron variant, grew substantially in February 2022 during the transition from winter into spring. The daily number of reported cases began to decline quickly in a few days after social distancing regulations were tightened and rapid antigen test (RAT) kits were largely distributed. How the non-pharmaceutical interventions (NPIs) and seasonal factors (temperature and relative humidity) could affect the spread of Omicron remains unknown. MethodsWe developed a model with stratified immunity, to incorporate antibody responses, together with changes in mobility and seasonal factors. After taking into account the detection rates of PCR test and RAT, we fitted the model to the daily number of reported cases between 1 February and 31 March, and quantified the associated effects of individual NPIs and seasonal factors on infection dynamics. FindingsAlthough NPIs and vaccine boosters were critical in reducing the number of infections, temperature was associated with a larger change in transmissibility. Cold days appeared to drive Re from about 2-3 sharply to 10.6 (95%CI: 9.9-11.4). But this number reduced quickly below one a week later when the temperature got warmer. The model projected that if weather in March maintained as Februarys average level, the estimated cumulative incidence could increase double to about 80% of total population. InterpretationTemperature should be taken into account when making public health decisions (e.g. a more relaxed (or tightened) social distancing during a warmer (or colder) season).

Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed no difference in the severity of different XBB variants.

The emergence of SARS-CoV-2 variants have raised concerns over the protective efficacy of the current generation of vaccines, and it remains unclear to what extent, if any, different variants impact the efficacy and effectiveness of various SARS-CoV-2 vaccines. We systematically searched for studies of SARS-CoV-2 vaccine efficacy and effectiveness, as well as neutralization data for variants, and used a previously published statistical model to predict vaccine efficacy against variants. Overall, we estimate the efficacy of mRNA-1273 and ChAdOx1 nCoV-19 against infection caused by the Delta variant to be 25-50% lower than that of prototype strains. The predicted efficacy against symptomatic illness of the mRNA vaccines BNT162b2 and mRNA-1273 are 95.1% (UI: 88.4-98.1%) and 80.8% (60.7-92.3%), respectively, which are higher than that of adenovirus-vector vaccines Ad26.COV2.S (44.8%, UI: 29.8-60.1%) and ChAdOx1 nCoV-19 (41.1%, 19.8-62.8%). Taken together, these results suggest that the development of more effective vaccine strategies against the Delta variant may be needed. Finally, the use of neutralizing antibody titers to predict efficacy against variants provides an additional tool for public health decision making, as new variants continue to emerge.

BackgroundCOVID-19 non-pharmaceutical interventions (NPIs) disrupted transmission of many infectious diseases worldwide. While disruption patterns are well-documented, systematic analysis of post-pandemic recovery trajectories across diverse pathogens remains limited. We examined disruption and recovery of 47 nationally notifiable diseases in Australia from 2015 to 2025. MethodsWe analysed NNDSS surveillance data for 47 diseases across six transmission modes, quantifying disruption using observed-to-expected (O/E) ratios against 2015-2019 baselines. We applied difference-in-differences (DiD) to estimate causal NPI effects, Kaplan-Meier survival analysis for time-to-recovery, and bootstrap 95% confidence intervals for cumulative immunity debt. ResultsDuring 2020-2021, 28 diseases decreased (median O/E 0.51), with border-sensitive and vaccine-preventable diseases most affected. DiD analysis estimated that border closures were associated with significantly greater suppression among import-dependent diseases (coefficient -0.50, 95% CI -0.90 to -0.10, p=0.016). By 2025, recovery was heterogeneous: 17 diseases exceeded baseline levels, 12 returned to expected levels, 15 remained below baseline (9 partially recovered, 6 in sustained suppression), and 3 had insufficient data for trajectory classification. Five diseases showed suppression-then-overshoot trajectories suggestive of immunity debt, though bootstrap 95% confidence intervals confirmed statistically significant cumulative excess for only one (rotavirus); for influenza, high baseline variability precluded statistical confirmation despite a large absolute overshoot. ConclusionsPost-pandemic disease recovery in Australia is heterogeneous and incomplete. Fifteen of 47 diseases have not returned to baseline levels by 2025, while 17 exhibit overshoot. These findings argue for differentiated surveillance of still-suppressed diseases and targeted catch-up vaccination in pandemic birth cohorts. Article summaryWe analysed disruption and recovery of 47 nationally notifiable diseases in Australia from 2015 to 2025, finding that 15 diseases remain below pre-pandemic levels three years after NPI relaxation. Border closures caused disproportionate suppression of import-dependent diseases, and recovery trajectories varied by disease characteristics, with immunity debt statistically confirmed for only one of five candidate diseases.

BackgroundSince the initial Wuhan outbreak, China has been containing COVID-19 outbreaks through its "dynamic zero-COVID" policy. Striking a balance between sustainability and cost-benefit, China has recently begun to adjust its COVID-19 response strategies, e.g. by announcing the "20 measures" on 11 November and further the "10 measures" on 7 December 2022. Strategies for safely exiting from dynamic zero-COVID (i.e. without catastrophically overburdening health systems and/or incurring unacceptably excessive morbidity and mortality) are urgently needed. MethodsWe use simulations to assess the respective and combined effectiveness of fourth-dose heterologous boosting, large-scale antiviral treatment and public health and social measures (PHSMs) that might allow China to further adjust COVID-19 response and exit from zero-COVID safely after 7 December 2022. We also assess whether local health systems can cope with the surge of COVID-19 cases posed by reopening, given that chunyun, a 40-day period with extremely high mobility across China associated with Spring Festival, will begin on 7 January 2023. FindingsReopening against Omicron transmission should be supported by the following interventions: 1) fourth-dose heterologous boosting 30-60 days before reopening by vaccinating 4-8% of the population per week with [≥]85% uptake across all ages; 2) timely antiviral treatment with [≥]60% coverage; 3) moderate PHSMs to reduce transmissibility by 47-69%. With fourth-dose vaccination coverage of 85% and antiviral coverage of 60%, the cumulative mortality burden would be reduced by 26-35% to 448-503 per million, compared with reopening without any of these interventions. Simultaneously reopening all provinces under current PHSMs would still lead to hospitalisation demand that are 1.5-2.5 times of surge hospital capacity (2.2 per 10,000 population per day). InterpretationAlthough the surge of disease burden posed by reopening in December 2022 - January 2023 would likely overload many local health systems across the country, the combined effect of vaccination, antiviral treatment and PHSMs could substantially reduce COVID-19 morbidity and mortality as China transits from dynamic-zero to normality. Planning for such a nationwide, coordinated reopening should be an urgent priority as part of the global exit from the acute phase of the COVID-19 pandemic. FundingCOVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention; Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong SAR; General Research Fund, Research Grants Council, Hong Kong Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and preprint archives for articles published up to 7 December 2021, that contained information about exit strategies of zero-COVID or reopening in China after the emergence of Omicron using the terms "China", "Omicron", "B.1.1.529", "COVID-19", "SARS-CoV-2", "vaccin*", "vaccine", "antiviral", "control measures", "non-pharmaceutical intervention", "public health and social measure", "zero-COVID", "exit strategy" and "reopen*". We only found one study by Wang et al (doi: 10.1101/2022.05.07.22274792) but they assessed the feasibility of sustaining SARS-CoV-2 containment with zero-COVID strategy in China. To our knowledge, there is no discussion of exit strategies of the zero-COVID strategy or assessment of feasibility of reopening in China. Added value of this studyReopening against Omicron transmission should be supported by the following interventions: 1) fourth-dose heterologous boosting 30-60 days before reopening by vaccinating 4-8% of the population per week with [≥]85% uptake across all ages; 2) timely antiviral treatment with [≥]60% coverage; 3) moderate PHSMs to reduce transmissibility by 47-69%. With fourth-dose vaccination coverage of 85% and antiviral coverage of 60%, the cumulative mortality burden would be reduced by 26-35% to 448-503 per million, compared with reopening without any of these interventions. Simultaneously reopening all provinces under current PHSMs would still lead to hospitalisation demand that are 1.5-2.5 times of surge hospital capacity (2.2 per 10,000 population per day). Implications of all the available evidenceAlthough the surge of disease burden posed by reopening in December 2022 - January 2023 would likely overload many local health systems across the country, the combined effect of vaccination, antiviral treatment and PHSMs could substantially reduce COVID-19 morbidity and mortality as China transits from dynamic-zero to normality. Planning for such a nationwide, coordinated reopening should be an urgent priority as part of the global exit from the acute phase of the COVID-19 pandemic.

BackgroundDespite the World Health Organizations declaration of the end of the COVID-19 pandemic, reinfection persists and continues to strain the global healthcare system. With the emergence of the most recent variant of SARS-CoV-2 named JN.1, retrospective analysis of epidemiological characteristics of previous cases involving the Omicron variant is essential to provide references for preventing reinfection caused by the ongoing new SARS-Cov-2 variants. MethodsThis retrospective cohort study included 6325 patients infected with SARS-CoV-2 during the Omicron-dominated outbreak (from December 2021 to May 2022) in Hong Kong. Statistical analysis was conducted to demonstrate the epidemiological characteristics and a logistic regression model was utilized to identify risk factors associated with reinfection. ResultsThe Omicron reinfection incidence was 5.18% (n = 353). No significant difference was observed in receiving mRNA (BNT162b2) vaccine and inactivated (CoronaVac) vaccine between reinfection and non-reinfection groups (p>0.05). Risk factors were identified as female gender (p<0.001), longer infection duration (p<0.05), comorbidity of eyes, ear, nose, throat disease (p<0.01), and severe post-infection impact on daily life and work (p<0.05), while [&ge;]70 years old (p<0.05) and vaccination after primary infection (p<0.01) were associated with a lower risk of reinfection. The prevalence of most symptoms after reinfection was lower than the first infection, except for fatigue. ConclusionNo significant difference in mRNA (BNT162b2) vaccine and inactivated (CoronaVac) vaccine against reinfection. Post-infection vaccination could lower the risk of reinfection, which potentially inform the development of preventive measures including vaccination policies against potential new SARS-Cov-2 variants.

BackgroundHIV-exposed uninfected infants (HEU) experience appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This may be due to some genetic factors that could alter the immune system. We thus sought to determine the distribution of Killer Cells Immunoglobulin-Like Receptor (KIR) genes in HEU versus HUU, and study the association between KIR profiling and occurrence of infection-related hospitalization. MethodsA cohort-study was conducted from May 2019 to April 2020 among HEU and HUU, followed-up at birth, week 6, 12, 24 and 48, in reference pediatric centers in Yaounde, Cameroon. Infant HIV status was determined, types of infections were analyzed, and 15 KIR genes were investigated using the sequence specific primer polymerase chain reaction (PCR-SSP) method. Rate of KIR genes and infection-related hospitalizations were compared in HEU versus HUU, with p<0.05 considered statistically significant. ResultsIn this cohort, a total of 19 infection-related hospitalizations occurred in 66 infants (14.81%, 04/27 HUU and 38.46%, 15/39 HEU, p=0.037), the majority occurring during the first 24 weeks of life: 10 (25.64%) HEU and 03 (11.11%) HUU, p=0.14. At week 48 (39 HEU and 27 HUU), the relative risk (RR) for infection-related hospitalizations was 2.42 (95% CI: 1.028-5.823) for HEU versus HUU, with aOR 3.59 (95% CI: 1.037-12.448). Incidence of hospitalization was 3.2 (95% CI: 1.63-7.14) per 100 infant-months among HEU versus 1.2 (95% CI: 0.57-3.60) in HUU, and RR was 2.22 (95% CI: 0.50-9.39). KIR2DL1 gene was significantly higher in HUU versus HEU (OR= 0.183, 95%CI: 0.053-0.629; p=0.003), and the absence of KIR2DL1 was significantly associated with infection-related hospitalization (p<0.001; OR=0.063; 95%CI: 0.017-0.229). ConclusionCompared to HUU, the vulnerability of HEU is driving by KIR2DL1, indicating the protective role of this KIR against infection and hospitalizations.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. While current vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections (i.e. irrespective of symptoms) remains sparse. We addressed this knowledge-gap using a community-wide serosurvey with 5,310 subjects by estimating how vaccination histories modulated risk of infection in Hong Kong (which was largely infection naive) during a large wave of Omicron epidemic during January-July 2022. We estimated that Omicron infected 45% (41-48%) of the Hong Kong population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection (VE of 47% (95% credible interval 34-68%) and 70% (43-99%) for three and four doses of BNT162b2 respectively; VE of 31% (1-73%) and 59% (10-99%) for three and four doses of CoronaVac respectively) seven days after vaccination, but protection waned with half-lives of 15 (3-47) weeks for BNT162b2 and 5 (1-37) weeks for CoronaVac. Our findings suggest that booster vaccination can temporarily enhance population immunity ahead of anticipated waves of infections.

Initial cases of COVID-19 reported in Hong Kong were mostly imported from China. However, most cases reported in February 2020 were locally-acquired infections, indicating local community transmissions. We extracted the demographic, clinical and epidemiological data from 50 COVID-19 patients, who accounted for 53.8% of the cases in Hong Kong by February 2020. Whole-genome sequencing of the SARS-CoV-2 were conducted to determine the phylogenetic relatedness and transmission dynamics. Only three (6.0%) patients required ICU admission. Phylogenetic analysis identified six transmission clusters. All locally-acquired cases harboured a common mutation Orf3a G251V and were clustered in two subclades in global phylogeny of SARS-CoV-2. The estimated time to the most recent common ancestor of local COVID-2019 outbreak was December 24, 2019 with an evolutionary rate of 3.04x10-3 substitutions per site per year. The reproduction number value was 1.84. Social distancing and vigilant epidemiological control are crucial to the containment of COVID-19 transmission. Article summary linesA combined epidemiological and phylogenetic analysis of early COVID-19 outbreak in Hong Kong revealed that a SARS-CoV-2 variant with ORF3a G251V mutation accounted for all locally acquired cases, and that asymptomatic carriers could be a huge public health risk for COVID-19 control.

BackgroundEarly-onset bowel cancer incidence (age <50 years) has increased worldwide and is highest in Australia, but how this varies across histology and anatomical site remains unclear. We aimed to investigate appendiceal, proximal colon, distal colon, rectal, and anal cancer incidence trends by age and histology in Australia. MethodsCancer incidence rate data were obtained from all Australian cancer registries (1990-2020 period). Birth cohort-specific incidence rate ratios (IRRs) and annual percentage change in rates were estimated using age-period-cohort modelling and joinpoint regression. FindingsAfter excluding neuroendocrine neoplasms, early-onset cancer incidence rose 5-9% annually, yielding 5,341 excess cases (2 per 100,000 person-years; 12% appendix, 45% colon, 36% rectum, 7% anus; 20-214% relative increase). Trends varied by site, period, and age: appendiceal cancer rose from 1990-2020 in 30-49-year-olds; colorectal cancers rose from around 1990-2010 in 20-29-year-olds and from 2010-2020 in 30-39-year-olds; anal cancer rose from 1990-2009 in 40-49-year-olds. Across all sites, IRRs increased with successive birth cohorts since 1960. Notably, adenocarcinoma incidence in the 1990s versus 1950s birth cohort was 2-3-fold for colorectum and 7-fold for appendix. The greatest subtype-specific increases occurred for appendiceal mucinous adenocarcinoma, colorectal non-mucinous adenocarcinoma, and anal squamous cell carcinoma. Only later-onset (age [&ge;]50) colorectal and anal adenocarcinoma rates declined. Appendiceal tumours, neuroendocrine neoplasms (all sites), anorectal squamous cell carcinomas, and colon signet ring cell carcinomas rose across early-onset and later-onset strata. InterpretationAppendiceal, colorectal, and anal cancer incidence is rising in Australia with variation across age and histology, underscoring the need to identify factors driving these trends. FundingALM is supported by an Australian Government Research Training Program Scholarship, Rowden White Scholarship, and WP Greene Scholarship. DDB is supported by a National Health and Medical Research Council of Australia (NHMRC) Investigator grant (GNT1194896), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to The Colon Cancer Family Registry (CCFR, www.coloncfr.org) from the National Cancer Institute (NCI), National Institutes of Health (NIH) [award U01 CA167551]. MAJ is supported by an NHMRC Investigator grant (GNT1195099), a University of Melbourne Dame Kate Campbell Fellowship, and by funding awarded to the CCFR from NCI, NIH [award U01 CA167551].

BackgroundReduced influenza transmission during the COVID-19 pandemic prompted concern about waning of population immunity that could lead to subsequent surges in circulation. We evaluated this by comparing longitudinal influenza antibody titers in Michigan and Hong Kong, two regions with reduced influenza transmission during the COVID-19 pandemic. MethodsIn two prospective cohort studies (HIVE, Michigan; EPI-HK, Hong Kong), we analyzed longitudinal serum samples collected from 2020 through 2023 from participants without documented influenza virus infection or vaccination. Sera were tested using hemagglutination inhibition assays (HAI) against relevant vaccine strains. Geometric mean titers (GMTs) and fold changes were estimated by region and time. Linear mixed-effects models were used to assess temporal trends. ResultsWe analyzed 173 sera from 57 HIVE participants and 259 sera from 60 EPI-HK participants. Initial GMTs in 2020-21 ranged from 12.3-123.4 in HIVE and 6.3-40.9 in EPI-HK (B/Yamagata-H1N1). Fold changes in GMTs ranged from 1.2-2.6 in HIVE and 0.7-1.0 in EPI-HK. In HIVE models, no significant change in HAI titers over time was detected. In EPI-HK, small but statistically significant monthly declines were observed for select H1N1 (A/Michigan) and H3N2 (A/Hong Kong) strains (e.g., A/Hong Kong: -0.98%, 95% CI: -1.82% to -0.11%). ConclusionMinimal HAI titer waning was observed in both regions. In some cases, antibody levels increased in Michigan, possibly indicating cryptic circulation of strains prior to the 2022/23 influenza season. These findings do not support an "immunity debt" during pandemic restrictions and could help explain the lack of a substantial surge in influenza impact after the COVID-19 pandemic.

In the wake of Hong Kongs zero-COVID policy, this study comprehensively analyses the epidemiological shift in respiratory viruses among hospitalized pediatric patients. The research leverages a unique natural experiment created by the policys stringent measures, which led to a significant reduction in virus circulation from 2020 to early 2023. The study highlights two distinct periods: pre-COVID-19 and post-mask mandate. We used pediatric hospitalization records from January 2015 to December 2019 and March 2023 to February 2024 to reveal a notable rebound in respiratory viruses. The age-stratified analysis indicated a shift in virus susceptibility. The odds ratio of having a co-infection was significantly increased in hospitalized children aged <1 to 12 years old during the post-COVID-19 mask mandate. Moreover, the adenovirus infection in younger children was more prominent, while RSV expanded its prevalence to older children aged>6 years old and raised health concerns. The study underscores the potential long-term impacts of interrupted virus exposure on childrens immune development and the need for vigilant monitoring of respiratory virus trends. It calls for further research to elucidate the causal relationships between SARS-CoV-2 exposure, subsequent respiratory virus susceptibility, and the implications for paediatric health in the post-pandemic era. Highlights- Children (4.37 {+/-} 0.05 years old) hospitalized after COVID-19 and tested for respiratory viruses were significantly older than those (3.49 {+/-} 0.03 years old) before COVID-19. - The odds ratio of having a co-infection was significantly increased in hospitalized children aged <1 to 12 years old during the post-COVID-19 era. - In the post-COVID-19 era, the adenovirus infection in younger children was more prominent while RSV expanded its prevalence to older children aged>6 years old

BackgroundWhen a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and also for public health surveillance. Tracking case numbers over time allows us to determine speed of spread and the effectiveness of interventions. Changing case definitions during an epidemic can affect these inferences. MethodsWe examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used simple models assuming exponential growth and then exponential decay to estimate how changes in the case definitions affected the numbers of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic. FindingsFrom January through to early March 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. As of February 20, there were 55,508 confirmed cases reported in mainland China. We estimated that when the case definitions were changed from version 1 to 2, version 2 to 4 and version 4 to 5, the proportion of infections being detected as cases were increased by 7.1-fold (95% credible interval (CI): 4.8, 10.9), 2.8-fold (95% CI: 1.9, 4.2) and 4.2-fold (95% CI: 2.6, 7.3) respectively. If the fifth version of the case definition had been applied throughout the outbreak, we estimated that by February 20 there would have been 232,000 (95% CI: 161,000, 359,000) confirmed cases. InterpretationThe case definition was initially narrow, but was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan or other known cases. This should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias. FundingCommissioned grant from the Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region.

BackgroundDespite relatively few reports of residential case clusters of COVID-19, building-wide compulsory testing notices on residential apartment blocks are frequently applied in Hong Kong with the aim of identifying cases and reducing transmission. MethodsWe aimed to describe the frequency of residential case clusters and the efficiency of compulsory testing notices in identifying cases. The residences of locally infected COVID-19 cases in Hong Kong were grouped to quantify the number of cases per residence. Buildings targeted in compulsory testing notices were matched with the residence of cases to estimate the number of cases identified. ResultsWe found that most of the residential buildings (4246/7688, 55.2%) with a confirmed COVID-19 case had only one reported case. In the fourth and the fifth epidemic wave in Hong Kong, we estimated that compulsory testing notices detected 29 cases (95% confidence interval: 26, 32) and 46 cases (44, 48) from every 100 buildings tested (each with hundreds of residents), respectively. Approximately 13% of the daily reported cases were identified through compulsory testing notices. ConclusionsCompulsory testing notices can be an essential method when attempting to maintain local elimination ( zero covid) and most impactful early in an epidemic when the benefit remains of stemming a new wave. Compulsory testing therefore appears to be a relatively inefficient control measure in response to sustained community transmission in the community.

BackgroundA range of public health measures have been implemented to delay and reduce local transmission of COVID-19 in Hong Kong, and there have been major changes in behaviours of the general public. We examined the effect of these interventions and behavioral changes on the incidence of COVID-19 as well as on influenza virus infections which may share some aspects of transmission dynamics with COVID-19. MethodsWe reviewed policy interventions and measured changes in population behaviours through two telephone surveys, on January 20-23 and February 11-14. We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt), for COVID-19 and influenza A(H1N1). FindingsCOVID-19 transmissibility has remained at or below 1, indicating successful containment to date. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% confidence interval, CI: 34% to 53%) reduction in transmissibility in the community, and a 33% (95% CI: 24% to 43%) reduction in transmissibility based on paediatric hospitalization rates. In the two surveys we estimated that 74.5% and 97.5% of the general adult population wore masks when going out, and 61.3% and 90.2% avoided going to crowded places, respectively. ImplicationsContainment measures, social distancing measures and changes in population behaviour have successfully prevented spread of COVID-19. The social distancing measures and behavioural changes led to a substantial reduction in influenza transmission in early February 2020. However, it may be challenging to avoid fatigue and sustain these measures and population behaviours as COVID-19 continues to spread globally. FundingHealth and Medical Research Fund, Hong Kong

The Omicron subvariant BA.2 caused the start of the fifth epidemic wave in Hong Kong in early 2022, leading to a significant outbreak and triggering more people get immunized in a population with relatively low vaccine coverage. About half a year later, a second outbreak, largely dominated by BA.4 and BA.5 subvariants, began to spread, which peaked within few months. How the waning of the vaccine protection and the immune escape properties together with other factors, including social distancing and outdoor temperature, drove the second surge of infections is unknown. The challenge is that basic epidemic modeling is not able to capture longitudinal change in vaccine waning and dose interval. We developed mathematical equations to formulate continuous change of vaccine waning after observing empirical serological data and incorporate them into a multi-strain discrete-time SEIR (Susceptible-Exposed-Infectious-Removed) model. Using the reported cases during the first outbreak as the training set together with daily vaccination rates, population mobility and temperature, the model successfully predicted the second surge and the replacement by BA.4/5, leading to a cumulative number of cases about 543,600 (7.27% of total population). If vaccine protection maintained without decreasing, the number of predicted cumulative cases reduced 35%. If perfect vaccine coverage reached (100%) by 1st June, the number of cases was only partially reduced 18.65%. Moderate level of social distancing (10% reduction in population mobility) reduced only 13.78% cases, which was not able to prevent the second surge. The results suggest future local outbreaks will remain as long as new immune escape happens with waning immunity, even if the moderate level of social distancing is present. Therefore, a more accurate model forecasting considering waning immunity remains needed in order to allow a better preparation of the next outbreaks.

BackgroundWhile Bangladesh has started its mass COVID-19 vaccination drive, it is struggling to cover its huge population similar to other low- and middle-income countries due to the lack of vaccine availability. One of the major remittance sources for Bangladesh is its migrant workers who are required to receive mRNA vaccines to return to their jobs. Despite reports of higher efficacy of mRNA vaccine against COVID-19, breakthrough infection cases are arising especially with the emergence of Delta variant. It is highly important to understand the post-vaccination immune response and breakthrough infections in different populations so that the necessity of booster dosage can be assessed properly. MethodsWe observed post BNT162b2 full vaccination immune response in a small older group (mean age= 59.5{+/-}5.44 years) of migrant workers (n=10) for six months at the Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh. The plasma samples from the participants were collected after 14 days, 2 months, 3 months, 4 months, 5 months, and 6 months of receiving the 2nd dose of the BNT162b2 vaccine. Anti S1 RBD IgG responses were measured as optical density ratios using a commercially available ELISA kit. ResultsAll 10 of the participants were male migrant workers and none of them had a history of previous COVID-19 infection. The median antibody response [IQ1:IQ3] was 9.05 [7.53; 10.0] on day 14 then it increases to 13.6 [12.0; 14.0] at the second month which gradually decreased to a median of 8.63 [8.34; 9.37] on the 6th-month post-vaccination. There were two breakthrough infection cases after receiving the second dose and the antibody responses were highly increased in the following months. Two of the breakthrough cases were diagnosed with mild COVID-19 as the symptom duration was less than 3 days with no respiratory complications and no hospital admission were required. ConclusionsThe BNT162b2 mRNA vaccine produces a strong immune response that sustains at least 6 months after getting fully vaccinated. But even after getting fully vaccinated people are susceptible to breakthrough infections that are not severe and boost the immune response greatly offering a hybrid immunity from both vaccine and natural infection. Hence, it is still important to fully vaccinate a greater number of people rather than thinking of offering booster dosage to a privileged population out of the fear of breakthrough cases. If the LMICs can quickly cover at least 80% of their population with usual priority targets (healthcare workers, migrant workers, older people, etc.) then a global risk reduction and pandemic control would be possible that will allow additional variant-specific boosters for targeted populations if evidence support.

BackgroundBBIBP-CorV vaccine with two doses and an interval of 3-4 weeks had been proved to have good immunogenicity and efficacy as well as an acceptable safety profile according to our initial research and other similar studies. Maintaining adequate neutralizing antibody levels is also necessary for long-term protection, especially in the midst of the COVID-19 pandemic. Our aim was to evaluate the immune persistence of neutralizing antibody elicited by BBIBP-CorV vaccines with day 0-14, 0-21 and 0-28 schedule, and assess the immunogenicity and safety of a homologous booster dose in the high-risk occupational population aged 18-59 years. MethodsA total of 809 eligible participants, aged 18-59 years, were recruited and randomly allocated to receive BBIBP-CorV vaccine with day 0-14, 0-21 or 0-28 schedule respectively between January and May 2021 in Taiyuan City, Shanxi Province, China among the public security officers and the airport ground staff in initial study. In this secondary study, the responders (GMT [&ge;] 16) at day 28 after priming two-dose vaccine were followed up at months 3, 6 and 10 to evaluate the immune persistence of three two-dose schedules. At month 10, eligible participants of three two-dose schedules were received a homologous booster dose respectively (hereafter abbreviated as 0-14d-10m group, 0-21d-10m group and 0-28d-10m group), and followed up at day 28 post-booster to assess the safety and immunogenicity of the booster dose. The contents of follow-up included the blood samples, oropharyngeal/nasal swabs, and adverse reactions collection. The main outcomes of the study included geometric mean titers (GMT) of neutralizing antibody to live SARS-CoV-2, the positive rates of different criteria and the constituent ratio of GMT of neutralizing antibodies at different follow-up point. Meanwhile, we explored the kinetics of antibody levels of different vaccination regimens by generalized estimating equations (GEE) and used exponent curve model to predict the duration of maintaining protected antibody after the booster dose. We also determined predictors of maintaining protected antibody level within 10 months after the second dose by Cox proportional hazards regression model and nomogram. The trial was registered with ChiCTR.org.cn (ChiCTR2100041705, ChiCTR2100041706). ResultsThe number of 241, 247 and 256 responders (GMT [&ge;] 16) at day 28 after two-dose BBIBP-CorV vaccine in 0-14d, 0-21d and 0-28d schedule were followed-up at months 3, 6, and 10 for immune persistence evaluation. At month 10, a total of 390 participants were eligible and received a booster dose with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group respectively, of whom 74.1% (289/390) were male, with a mean age of 37.1{+/-}10.3 years. The GMT of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3 (GMT: 71.6 & 64.2 vs 46.4, P<0.0001), month 6 (GMT: 47.1 & 42.8 vs 30.5, P < 0.0001) and month 10 (GMT: 32.4 vs 20.3, P < 0.0001; 28.8 vs 20.3, P=0.0004) after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics (P=0.67). At 28 days after booster dose, a remarkable rebound in neutralizing antibody (GMT: 246.2, 277.5 and 288.6) were observed in three groups, respectively. Notably, the GMT after booster dose was not affected by priming two-dose schedule. The predictive duration of neutralizing antibody declining to the cutoff level of positive antibody response may be 18.08 months, 18.83 months and 19.08 months after booster dose in three groups, respectively. Long-term immune persistence within 10 months after the second dose was associated with age<40, female, and history of influenza vaccination. All adverse reactions were mild after the booster injection. None of the participants were infected SARS-CoV-2 during the trial period. ConclusionsThe priming two-dose BBIBP-CorV vaccine with 0-28 days and 0-21 days schedule could lead a longer persistence of neutralizing antibody than 0-14 days schedule. Maintaining long-term immune persistence was also associated with age<40, female, and history of influenza vaccination. Regardless of priming two-doses vaccination regimens, a homologous booster dose led to a strong rebound in neutralizing antibody and might elicit satisfactory persistent immunity.

To describe characteristics of COVID-19 outbreaks in Australia to guide policy development for mitigation of future outbreaks, we conducted a retrospective analysis of COVID-19 outbreaks affecting two or more people reported to COVID-Net--an Australian national surveillance network--from 28 January until 27 December 2020. The COVID-Net surveillance network covered all Australian states and territories, with an estimated population of 25,649,985 persons as at 31 June 2020. We reported the epidemiology of COVID-19 outbreaks in Australia, including the setting in which they occurred, size, and duration. 853 outbreaks of COVID-19 were reported; associated with 13,957 confirmed cases, of whom 2,047 were hospitalised, and 800 died. The pattern of outbreaks followed a similar trend to the epidemic in Australia, defined by two distinct peaks in mid-March and July. Victoria reported the greatest number of outbreaks across all settings aligned with the second wave of infections. Outbreaks most commonly occurred in the workplace/industry setting (22%, 190/853), followed by education (14%, 122/853), residential aged care (13%, 114/853) and hospitals (10%, 83/853). The majority (40%, 340/853) of outbreaks had 6 to 24 cases, and the median outbreak duration increased in proportion with the number of associated cases. This report summarising COVID-19 outbreaks in Australia identifies settings of highest risk. Surveillance of outbreaks informs our understanding of transmission dynamics in Australia relative to national and jurisdictional interventions. For settings that are high risk for COVID-19, it is important to prioritise planning, surveillance, and implementation of control measures.

BackgroundRising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10g V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. MethodsWe conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10g V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. ResultsThe third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10g V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. ConclusionsA homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.