Assessment of the impact of the vaccine pass policy on COVID-19 vaccine hesitancy and uptake among Chinese adults in Hong Kong.

BACKGROUND: Recognising the importance of attaining high vaccine coverage to mitigate the COVID-19 impact, a Vaccine Pass scheme was implemented during and after the first large Omicron wave with high mortality in older ages in Hong Kong in early 2022 requiring three doses by June 2022. We did not identify any studies evaluating the policy impact of vaccination mandates with vaccine uptake over whole policy period of time in a Chinese population. We aim to evaluate the impact of the Vaccine Pass policy on COVID-19 vaccine uptake in adults in a Chinese population in Hong Kong. METHODS: We analysed patterns in vaccine uptake and hesitancy using local data from population vaccine registry and 32 cross-sectional telephone surveys conducted from October 2021 to December 2022. The association of Vaccine Pass phases with vaccine uptake was examined using logistic regression analyses, taking into account covariates including self-risk perception, perceived self-efficacy in preventing COVID-19 and trust in government in pandemic control as well as physical distancing measures and demographics. RESULTS: The uptake of primary series and third doses was positively significantly associated with the successive stages of Vaccine Pass implementation (adjusted odds ratios ranged from 2.41 to 7.81). Other statistically significant drivers of uptake included age group, chronic condition, higher perceived personal susceptibility to COVID-19, higher trust in government, and higher educational attainment. CONCLUSION: Vaccine uptake in older adults was observed to have increased by a greater extent after the policy annoucement and implementation, under the contextual changes during and after a large Omicron wave with high mortality in Hong Kong in early 2022. Since the policy withdrawal the uptake of further booster doses has been very low in all ages. We suggest that improving voluntary booster uptake in older adults should be prioritized.

Decreased risk of non-influenza respiratory infection after influenza B virus infection in children.

Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009-2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27-0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.

Interpretations of Studies on SARS-CoV-2 Vaccination and Post-acute COVID-19 Sequelae.

This article discusses causal interpretations of epidemiologic studies of the effects of vaccination on sequelae after acute severe acute respiratory syndrome coronavirus 2 infection. To date, researchers have tried to answer several different research questions on this topic. While some studies assessed the impact of postinfection vaccination on the presence of or recovery from post-acute coronavirus disease 2019 syndrome, others quantified the association between preinfection vaccination and postacute sequelae conditional on becoming infected. However, the latter analysis does not have a causal interpretation, except under the principal stratification framework-that is, this comparison can only be interpreted as causal for a nondiscernible stratum of the population. As the epidemiology of coronavirus disease 2019 is now nearly entirely dominated by reinfections, including in vaccinated individuals, and possibly caused by different Omicron subvariants, it has become even more important to design studies on the effects of vaccination on postacute sequelae that address precise causal questions and quantify effects corresponding to implementable interventions.

Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children.

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.

Hemagglutination inhibition antibody titers mediate influenza vaccine efficacy against symptomatic influenza A(H1N1), A(H3N2), and B/Victoria infections.

BACKGROUND: The hemagglutination inhibition antibody (HAI) titer mediates only a part of vaccine-induced protection against influenza virus infections. Using causal mediation analysis, we quantified the proportion of vaccine efficacy mediated by post-vaccination HAI titers. METHODS: Causal mediation analyses were conducted using data collected for a randomized, active-comparator controlled, phase 3 trial of a candidate inactivated, split-virion seasonal quadrivalent influenza vaccine (QIV) in children aged 3 to 8 years conducted from October 2010 to December 2011 in eight countries. Vaccine efficacy was estimated with a weighted Cox proportional hazards regression model. Estimates were decomposed into the direct and indirect effects mediated by post-vaccination HAI titers. RESULTS: The proportions of vaccine efficacy mediated by post-vaccination HAI titers were estimated to be 22% (95% CI: 18%, 47%) for influenza A(H1N1), 20% (95% CI: 16%, 39%) for influenza A(H3N2), and 37% (95% CI: 26%, 85%) for influenza B/Victoria. CONCLUSIONS: HAI titers partially mediate influenza vaccine efficacy against influenza A(H1N1), A(H3N2), and B/Victoria. Our estimates were lower than previous studies, possibly reflecting expected heterogeneity in antigenic similarity between vaccine and circulating viruses across seasons. Data from more influenza seasons are needed to understand better the mediating effects of HAI titers on vaccine efficacy.

Association of COVID-19 vaccination with duration of hospitalization in older adults in Hong Kong.

INTRODUCTION: The association between COVID-19 vaccination and length of hospital stay may provide further insight into vaccination benefits, but few studies have investigated such associations in detail. We aimed to investigate the association between COVID-19 vaccination and length of hospital stay in COVID-19 patients during Omicron waves in Hong Kong, and explore potential predictors. METHODS: This retrospective cohort study was conducted on local patients aged ≥60 years who were admitted due to COVID-19 infection in Hong Kong in 2022, from 1 February to 22 November, and with 28 days of follow-up since admission. The exposure was either not vaccinated; or having received 2/3/4 doses of CoronaVac (Sinovac); or 2/3/4 doses of BNT162b2 (BioNTech/Fosun Pharma/Pfizer). Length of stay in hospital was the main outcome. Accelerated failure time models were used to quantify variation in hospital stay for vaccinated compared with unvaccinated patients, accounting for age, sex, comorbidity, type of vaccine and number of doses received, care home residence and admission timing; stratified by age groups and epidemic waves. RESULTS: This study included 32,398 patients aged 60 years and above for main analysis, their median (IQR) age was 79 (71-87) years, 53% were men, and 40% were unvaccinated. The patients were stratified by confirmation prior to or since 23 May 2022, resulting in a sample size of 15,803 and 16,595 in those two waves respectively. Vaccinated patients were found to have 13-39% shorter hospital stay compared to unvaccinated patients. More vaccine doses received were associated with shorter hospital stay, and BNT162b2 recipients had slightly shorter hospital stays than CoronaVac recipients. CONCLUSION: Vaccination was associated with reduced hospital stay in breakthrough infections. Increased vaccination uptake in older adults may improve hospital bed turnover and public health outcomes especially during large community epidemics.

Comparative epidemiology of outbreaks caused by SARS-CoV-2 Delta and Omicron variants in China.

From 2020 to December 2022, China implemented strict measures to contain the spread of severe acute respiratory syndrome coronavirus 2. However, despite these efforts, sustained outbreaks of the Omicron variants occurred in 2022. We extracted COVID-19 case numbers from May 2021 to October 2022 to identify outbreaks of the Delta and Omicron variants in all provinces of mainland China. We found that omicron outbreaks were more frequent (4.3 vs. 1.6 outbreaks per month) and longer-lasting (mean duration: 13 vs. 4 weeks per outbreak) than Delta outbreaks, resulting in a total of 865,100 cases, of which 85% were asymptomatic. Despite the average Government Response Index being 12% higher (95% confidence interval (CI): 9%, 15%) in Omicron outbreaks, the average daily effective reproduction number (Rt) was 0.45 higher (95% CI: 0.38, 0.52, p < 0.001) than in Delta outbreaks. Omicron outbreaks were suppressed in 32 days on average (95% CI: 26, 39), which was substantially longer than Delta outbreaks (14 days; 95% CI: 11, 19; p = 0.004). We concluded that control measures effective against Delta could not contain Omicron outbreaks in China. This highlights the need for continuous evaluation of new variants' epidemiology to inform COVID-19 response decisions.

High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains.

The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year-although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and a computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.

Influenza vaccine effectiveness against hospitalizations associated with influenza A(H3N2) in Hong Kong children aged 9 months to 17 years, June-November 2023.

A test negative study was carried out from 13 June through to 15 November 2023 enrolling 3183 children hospitalized with acute respiratory illness in Hong Kong. Influenza A and B viruses were detected in 528 (16.6%) children, among which 419 (79.4%) were influenza A(H3N2). The overall vaccine effectiveness against hospitalization associated with any influenza virus infection was estimated as 22.4% (95% CI: -11.7%, 46.1%), and against influenza A(H3N2) specifically was 14.3% (95% CI: -29.2%, 43.2%). Despite the moderate to low VE estimated here, which could be a result of waning immunity and antigenic drift, influenza vaccination remains an important approach to reduce the impact of influenza in children.

Modeling the health impact of increasing vaccine coverage and nonpharmaceutical interventions against coronavirus disease 2019 in Ghana.

Seroprevalence studies assessing community exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana concluded that population-level immunity remained low as of February 2021. Thus, it is important to demonstrate how increasing vaccine coverage reduces the economic and public health impacts associated with SARS-CoV-2 transmission. To that end, this study used a Susceptible-Exposed-Presymptomatic-Symptomatic-Asymptomatic-Recovered-Dead-Vaccinated compartmental model to simulate coronavirus disease 2019 (COVID-19) transmission and the role of public health interventions in Ghana. The impact of increasing vaccination rates and decline in transmission rates due to nonpharmaceutical interventions (NPIs) on cumulative infections and deaths averted was explored under different scenarios. Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) was used to investigate the uncertainty and sensitivity of the outcomes to the parameters. Simulation results suggest that increasing the vaccination rate to achieve 50% coverage was associated with almost 60,000 deaths and 25 million infections averted. In comparison, a 50% decrease in the transmission coefficient was associated with the prevention of about 150,000 deaths and 50 million infections. The LHS-PRCC results indicated that in the context of vaccination rate, cumulative infections and deaths averted were most sensitive to vaccination rate, waning immunity rates from vaccination, and waning immunity from natural infection. This study's findings illustrate the impact of increasing vaccination coverage and/or reducing the transmission rate by NPI adherence in the prevention of COVID-19 infections and deaths in Ghana.

Reported effectiveness of COVID-19 monovalent booster vaccines and hybrid immunity against mild and severe Omicron disease in adults: A systematic review and meta-regression analysis.

Background: Waning of COVID-19 vaccine efficacy/effectiveness (VE) has been observed across settings and epidemiological contexts. We conducted a systematic review of COVID-19 VE studies and performed a meta-regression analysis to improve understanding of determinants of waning. Methods: Systematic review of PubMed, medRxiv and the WHO-International Vaccine Access Center database summarizing VE studies on 31 December 2022. Studies were those presenting primary adult VE data from hybrid immunity or third/fourth mRNA COVID-19 monovalent vaccine doses [due to limited data with other vaccines] against Omicron, compared with unvaccinated individuals or individuals eligible for corresponding booster doses but who did not receive them. We used meta-regression models, adjusting for confounders, with weeks since vaccination as a restricted cubic spline, to estimate VE over time since vaccination. Results: We identified 55 eligible studies reporting 269 VE estimates. Most estimates (180/269; 67 %) described effectiveness of third dose vaccination; with 48 (18 %) and 41 (15 %) describing hybrid immunity and fourth dose effectiveness, respectively, mostly (200; 74 %) derived from test-negative design studies. Most estimates (176/269; 65 %) reported VE compared with unvaccinated comparison groups. Estimated VE against mild outcomes declined following third dose vaccination from 62 % (95 % CI: 58 % - 66 %) after 4 weeks to 48 % (41 % - 55 %) after 20 weeks. Fourth dose VE against mild COVID-19 declined from 48 % (41 % - 56 %) after 4 weeks to 47 % (19 % - 65 %) after 20 weeks. VE for severe outcomes was higher and declined in the three-dose group from 90 % (87 % - 92 %) after 4 weeks to 70 % (65 - 74 %) after 20 weeks. Conclusions: Time-since vaccination is an important determinant of booster dose VE, a finding which may support seasonal COVID-19 booster doses. Integration of VE and immunological parameters - and longer-term data including from other vaccine types - are needed to better-understand determinants of clinical protection.

Public Health Impact of Paxlovid as Treatment for COVID-19, United States.

We evaluated the population-level benefits of expanding treatment with the antiviral drug Paxlovid (nirmatrelvir/ritonavir) in the United States for SARS-CoV-2 Omicron variant infections. Using a multiscale mathematical model, we found that treating 20% of symptomatic case-patients with Paxlovid over a period of 300 days beginning in January 2022 resulted in life and cost savings. In a low-transmission scenario (effective reproduction number of 1.2), this approach could avert 0.28 million (95% CI 0.03-0.59 million) hospitalizations and save US $56.95 billion (95% CI US $2.62-$122.63 billion). In a higher transmission scenario (effective reproduction number of 3), the benefits increase, potentially preventing 0.85 million (95% CI 0.36-1.38 million) hospitalizations and saving US $170.17 billion (95% CI US $60.49-$286.14 billion). Our findings suggest that timely and widespread use of Paxlovid could be an effective and economical approach to mitigate the effects of COVID-19.

Key Challenges for Respiratory Virus Surveillance while Transitioning out of Acute Phase of COVID-19 Pandemic.

To support the ongoing management of viral respiratory diseases while transitioning out of the acute phase of the COVID-19 pandemic, many countries are moving toward an integrated model of surveillance for SARS-CoV-2, influenza virus, and other respiratory pathogens. Although many surveillance approaches catalyzed by the COVID-19 pandemic provide novel epidemiologic insight, continuing them as implemented during the pandemic is unlikely to be feasible for nonemergency surveillance, and many have already been scaled back. Furthermore, given anticipated cocirculation of SARS-CoV-2 and influenza virus, surveillance activities in place before the pandemic require review and adjustment to ensure their ongoing value for public health. In this report, we highlight key challenges for the development of integrated models of surveillance. We discuss the relative strengths and limitations of different surveillance practices and studies as well as their contribution to epidemiologic assessment, forecasting, and public health decision-making.

Effectiveness of mRNA BNT162b2 and inactivated CoronaVac vaccines against severe COVID-19 outcomes among non-hospitalised children aged 1-3 years with SARS-CoV-2 Omicron infection.

OBJECTIVES: Clinical evidence on the effectiveness of COVID-19 vaccines for children aged 1-3 years is scarce. The effectiveness of COVID-19 vaccines was evaluated among non-hospitalised children aged 1-3 years with SARS-CoV-2 Omicron infection in Hong Kong. METHODS: A retrospective cohort of all non-hospitalised children aged 1-3 years with confirmed SARS-CoV-2 infection between 4 August 2022 and 29 January 2023 in Hong Kong was analysed. Vaccinated group was defined as the recipients of one or more doses of CoronaVac or mRNA vaccine BNT162b2 (original, monovalent) at least 14 days prior to infection. Hazard ratios (HR) with 95% confidence intervals (95% CI) of study outcomes were estimated using Cox regression models. Effectiveness outcomes included 28-day all-cause mortality and COVID-19-related hospitalisation. RESULTS: A total of 5552 vaccinated patients and 5552 propensity-score matched controls (unvaccinated patients) were included for analysis. The cumulative incidence of COVID-19-related hospitalisation over 28 days was 2.3% and 2.9% in the vaccinated and control groups, respectively. There were no deaths in both groups. COVID-19 vaccination was associated with a significant reduction in 28-day COVID-19-related hospitalisation risk (HR=0.785, 95% CI=0.626-0.985, P=0.037), particularly for children aged 3 years, those who had received two or more vaccine doses, and those who received CoronaVac as the last dose. CONCLUSION: COVID-19 vaccination is associated with a significantly lower risk of 28-day COVID-19-related hospitalisation among infected children aged 1-3 years, particularly those who had received two or more vaccine doses. This observation emphasises the importance of completing the full two-dose or three-dose series to optimise vaccine effectiveness.

Dynamic predictors of COVID-19 vaccination uptake and their interconnections over two years in Hong Kong.

The global rollout of COVID-19 vaccines faces a significant barrier in the form of vaccine hesitancy. This study adopts a dynamic and network perspective to explore the determinants of COVID-19 vaccine uptake in Hong Kong, focusing on multi-level determinants and their interconnections. Following the framework proposed by the Strategic Advisory Group of Experts (SAGE), the study used repeated cross-sectional surveys to map these determinants at multiple levels and investigates their interconnections simultaneously in a sample of 15,179 over two years. The results highlight the dynamic nature of COVID-19 vaccine hesitancy in an evolving pandemic. The findings suggest that vaccine confidence attitudes play crucial roles in vaccination uptake, with their importance shifting over time. The initial emphasis on vaccine safety gradually transitioned to heightened consideration of vaccine effectiveness at a later stage. The study also highlights the impact of chronic condition, age, COVID-19 case numbers, and non-pharmaceutical preventive behaviours on vaccine uptake. Higher educational attainment and being married were associated with primary and booster vaccine uptake and it may be possible to leverage these groups as early innovation adopters. Trust in government acts as a crucial bridging factor linking various variables in the networks with vaccine confidence attitudes, which subsequently closely linked to vaccine uptake. This study provides insights for designing future effective vaccination programmes for changing circumstances.

Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation.

To date, there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant persons. This target trial emulation study aimed to address this gap by evaluating the use of nirmatrelvir/ritonavir in nonhospitalized pregnant women with symptomatic SARS-CoV-2 Omicron variant infection. Among patients diagnosed between 16 March 2022 and 5 February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or coronavirus disease 2019 (COVID-19) diagnosis. Primary outcomes were maternal morbidity and mortality index (MMMI), all-cause maternal death and COVID-19-related hospitalization, while secondary outcomes were individual components of MMMI, preterm birth, stillbirth, neonatal death and cesarean section. One-to-ten propensity-score matching was conducted between nirmatrelvir/ritonavir users and nonusers, followed by cloning, censoring and weighting. Overall, 211 pregnant women on nirmatrelvir/ritonavir and 1,998 nonusers were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28-day MMMI risk (absolute risk reduction (ARR) = 1.47%, 95% confidence interval (CI) = 0.21-2.34%) but not 28-days COVID-19-related hospitalization (ARR = -0.09%, 95% CI = -1.08% to 0.71%). Nirmatrelvir/ritonavir treatment was also associated with reduced risks of cesarean section (ARR = 1.58%, 95% CI = 0.85-2.39%) and preterm birth (ARR = 2.70%, 95% CI = 0.98-5.31%). No events of maternal or neonatal death or stillbirth were recorded. The findings suggest that nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant women with SARS-CoV-2 Omicron variant infection.

Effectiveness of Vaccines and Antiviral Drugs in Preventing Severe and Fatal COVID-19, Hong Kong.

We compared the effectiveness and interactions of molnupiravir and nirmatrelvir/ritonavir and 2 vaccines, CoronaVac and Comirnaty, in a large population of inpatients with COVID-19 in Hong Kong. Both the oral antiviral drugs and vaccines were associated with lower risks for all-cause mortality and progression to serious/critical/fatal conditions (study outcomes). No significant interaction effects were observed between the antiviral drugs and vaccinations; their joint effects were additive. If antiviral drugs were prescribed within 5 days of confirmed COVID-19 diagnosis, usage was associated with lower risks for the target outcomes for patients >60, but not <60, years of age; no significant clinical benefit was found if prescribed beyond 5 days. Among patients >80 years of age, 3-4 doses of Comirnaty vaccine were associated with significantly lower risks for target outcomes. Policies should encourage COVID-19 vaccination, and oral antivirals should be made accessible to infected persons within 5 days of confirmed diagnosis.

Estimation of the Time-Varying Effective Reproductive Number of COVID-19 Based on Multivariate Time Series of Severe Health Outcomes.

The time-varying effective reproduction number (Rt at time t) measures the transmissibility of SARS-CoV-2 and is conventionally based on daily case counts, which may suffer from time-varying ascertainment. We analyzed Rt estimates from case counts and severe COVID-19 (intensive care unit admissions, severe or critical cases, and mortality) across 2022 in Hong Kong's fifth and sixth waves of infection. Within the fifth wave, the severe disease-based Rt (3.5) was significantly higher than the case-based Rt (2.4) but not in the sixth wave. During periods with fluctuating underreporting, data based on severe diseases may provide more reliable Rt estimates.

Understanding paediatric COVID-19 vaccination during the pandemic: a prospective cohort and a population-based registry study.

Background: Despite the early demonstrated safety and effectiveness of COVID-19 vaccines in children, uptake was slow throughout the pandemic and remains low globally. Understanding vaccine refusal could provide insights to improving vaccine uptake in future pandemics. Methods: In a population-wide registry of all COVID-19 paediatric vaccination appointments, we used interrupted time series analysis to evaluate the impact of public policies. In a population-based cohort of adults, we used population attributable fractions to assess the individual and joint contributions of potential determinants to paediatric COVID-19 vaccination, and used mediation analysis to identify modifiable mediators between political views and paediatric vaccination. Findings: School vaccination requirements were associated with an increase in vaccination appointments by 278.7% (95% CI 85.3-673.9) in adolescents aged 12-17 and 112.8% (27.6-255.0) in children aged 5-11. Government-mandated vaccine pass, required for entry into restaurants, shopping malls and supermarkets, was associated with increased vaccination appointments by 108.7% (26.6-244.0) in adolescents. The following four determinants may explain 82.5% (63.5-100.0) of the reasons why children were unvaccinated: familial political views, vaccine hesitancy for children, mistrust in doctors and academics, and vaccine misconceptions. The influence of political views may be mitigated since 95.9% (76.4-100.0) of its association with vaccine reluctance for adolescents was mediated by modifiable factors such as mistrust in health authorities and low vaccine confidence. Interpretation: School vaccination requirements and vaccine passes were associated with increased vaccine uptake. Clinicians should recognise that factors beyond health, such as political views, can influence paediatric vaccine uptake to a significant extent. Nonetheless, such influences could be mitigated by targeted interventions and public policies. Funding: Hong Kong Jockey Club Charities Trust, Research Grants Council, University Grants Committee, and Health Bureau.