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.

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'.

The association between circulating fatty acids and stroke in hypertensive patients.

BACKGROUND: Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients. METHODS: Eighty-nine pairs including 100 men and 78 women matched by sex and age were recruited. Each pair included a hypertensive patient within 48h of AIS onset and a hypertensive patient without stroke. Six circulating fatty acids were methylated before concentration determination which was repeated twice with percent recovery estimated. RESULTS: There were differences in educational level (P = 0.002) and occupation (P < 0.001) between stroke and non-stroke participants. All the 6 fatty acid levels were higher in non-stroke participants (P = 0.017 for palmitoleic acid, 0.001 for palmitic acid, <0.001 for linoleic acid, <0.001 for behenic acid, <0.001 for nervonic acid and 0.002 for lignoceric acid). In logistic regression analysis, AIS was inversely associated with fatty acid levels except for lignoceric acid. After adjustment for education and occupation, the palmitoleic acid and palmitic acid levels were no longer inversely associated with AIS. After further adjustment for systolic blood pressure, smoking, drinking, total cholesterol and triglyceride, the inverse associations of linoleic acid (OR = 0.965, 95%CI = 0.942-0.990, P = 0.005), behenic acid (OR = 0.778, 95%CI = 0.664-0.939, P = 0.009), nervonic acid (OR = 0.323, 95%CI = 0.121-0.860, P = 0.024) with AIS remained significant. CONCLUSIONS: Circulating fatty acids except lignoceric acid were inversely associated with AIS. Both USFAs and SFAs may have beneficial effect on stroke prevention in hypertensive population.

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.

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.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

Influenza Resurgence after Relaxation of Public Health and Social Measures, Hong Kong, 2023.

Soon after a mask mandate was relaxed (March 1, 2023), the first post-COVID-19 influenza season in Hong Kong lasted 12 weeks. After other preventive measures were accounted for, mask wearing was associated with an estimated 25% reduction in influenza transmission. Influenza resurgence probably resulted from relaxation of mask mandates and other measures.

COVID-19 Vaccination Willingness and Reasons for Vaccine Refusal.

Importance: Hong Kong was held as an exemplar for pandemic response until it recorded the world's highest daily COVID-19 mortality, which was likely due to vaccine refusal. To prevent this high mortality in future pandemics, information on underlying reasons for vaccine refusal is necessary. Objectives: To track the evolution of COVID-19 vaccination willingness and uptake from before vaccine rollout to mass vaccination, to examine factors associated with COVID-19 vaccine refusal and compare with data from Singapore, and to assess the population attributable fraction for vaccine refusal. Design, Setting, and Participants: This cohort study used data from randomly sampled participants from 14 waves of population-based studies in Hong Kong (February 2020 to May 2022) and 2 waves of population-based studies in Singapore (May 2020 to June 2021 and October 2021 to January 2022), and a population-wide registry of COVID-19 vaccination appointments. Data were analyzed from February 23, 2021, to May 30, 2022. Exposures: Trust in COVID-19 vaccine information sources (ie, health authorities, physicians, traditional media, and social media); COVID-19 vaccine confidence on effectiveness, safety, and importance; COVID-19 vaccine misconceptions on safety and high-risk groups; political views; and COVID-19 policies (ie, workplace vaccine mandates and vaccine pass). Main Outcomes and Measures: Primary outcomes were the weighted prevalence of COVID-19 vaccination willingness over the pandemic, adjusted incidence rate ratios, and population attributable fractions of COVID-19 vaccine refusal. A secondary outcome was change in daily COVID-19 vaccination appointments. Results: The study included 28 007 interviews from 20 waves of longitudinal data, with 1114 participants in the most recent wave (median [range] age, 54.2 years [20-92] years; 571 [51.3%] female). Four factors-mistrust in health authorities, low vaccine confidence, vaccine misconceptions, and political views-could jointly account for 82.2% (95% CI, 62.3%-100.0%) of vaccine refusal in adults aged 18 to 59 years and 69.3% (95% CI, 47.2%-91.4%) of vaccine refusal in adults aged 60 years and older. Workplace vaccine mandates were associated with 62.2% (95% CI, 9.9%-139.2%) increases in daily COVID-19 vaccination appointments, and the Hong Kong vaccine pass was associated with 124.8% (95% CI, 65.9%-204.6%) increases in daily COVID-19 vaccination appointments. Conclusions and Relevance: These findings suggest that trust in health authorities was fundamental to overcoming vaccine hesitancy. As such, engendering trust in health care professionals, experts, and public health agencies should be incorporated into pandemic preparedness and response.

Viral kinetics of SARS-CoV-2 following onset of COVID-19 in symptomatic patients infected with the ancestral strain and omicron BA.2 in Hong Kong: a retrospective observational study.

BACKGROUND: Assessment of viral kinetics of SARS-CoV-2 can inform on host immune responses to the virus and on the viral transmission potential. We aimed to characterise viral shedding kinetics by age, virus type, and clinical outcome, and to examine the potential effect of vaccination on viral shedding. METHODS: In this retrospective observational study, we analysed longitudinal data on cycle threshold (Ct) values of reverse-transcription quantitative PCR (RT-qPCR) assays of upper respiratory tract samples from symptomatic patients with COVID-19. Patients who were confirmed with COVID-19 with at least one Ct value of the RT-qPCR test available within 28 days after symptom onset, and discharged or died at the time of the analysis, were included in the study. Patients were isolated in hospitals in Hong Kong during three major epidemic waves dominated by the ancestral strain or omicron BA.2. We modelled the temporal trajectories of viral burden in these patients. Electronic medical records of the patients with COVID-19 were retrieved and linked to the patients' epidemiological information obtained from contact tracing. Patients who were infected outside Hong Kong, infected with variants other than the ancestral strain or omicron BA.2, not reporting any COVID-19 related symptoms, still hospitalised at the time of analysis, missing information on age, time of symptom onset, infection severity, vaccination or clinical outcome, infected more than once, or treated with nirmatrelvir-ritonavir or molnupiravir were excluded from analysis. The main outcome of this study is the temporal change of SARS-CoV-2 viral burden measured by Ct values of RT-qPCR tests in symptomatic patients with COVID-19. FINDINGS: Among 22 461 symptomatic patients with COVID-19 confirmed from July 1, 2020, to May 22, 2022, the estimated viral burden from a random-effects model indicated a longer duration of viral shedding in patients with more severe outcomes of infection (mean difference 13·1 days, 95% CI 12·9-13·3, for fatal vs mild-to-moderate) and in older patients (5·2, 5·0-5·5, for age ≥80 years vs 0-18 years). Vaccinated individuals with a breakthrough infection with the omicron BA.2 variant had a generally lower viral burden and shorter durations of viral shedding (mean difference of 2-4 days) over 4 weeks after onset than unvaccinated individuals infected with omicron BA.2, particularly in patients whose last dose of COVID-19 vaccine was received ≤90 days before symptom onset. Marginal differences in viral burden following symptom onset and the duration of viral shedding were observed between unvaccinated individuals infected with the ancestral strain and omicron BA.2. INTERPRETATION: The viral kinetics since symptom onset characterised for symptomatic patients with COVID-19 in our study show that previously vaccinated or younger individuals, or those with a milder infection, shed fewer viruses in a shorter period, implying possible transmission dynamics of SARS-CoV-2 and protective mechanisms of vaccination against infection and severe outcomes. FUNDING: Hong Kong Health and Medical Research Fund and Hong Kong Collaborative Research Fund.

The need for a clinical case definition in test-negative design studies estimating vaccine effectiveness.

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all groups consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

Reconstructing household transmission dynamics to estimate the infectiousness of asymptomatic influenza virus infections.

There has long been controversy over the potential for asymptomatic cases of the influenza virus to have the capacity for onward transmission, but recognition of asymptomatic transmission of COVID-19 stimulates further research into this topic. Here, we develop a Bayesian methodology to analyze detailed data from a large cohort of 727 households and 2515 individuals in the 2009 pandemic influenza A(H1N1) outbreak in Hong Kong to characterize household transmission dynamics and to estimate the relative infectiousness of asymptomatic versus symptomatic influenza cases. The posterior probability that asymptomatic cases [36% of cases; 95% credible interval (CrI): 32%, 40%] are less infectious than symptomatic cases is 0.82, with estimated relative infectiousness 0.57 (95% CrI: 0.11, 1.54). More data are required to strengthen our understanding of the contribution of asymptomatic cases to the spread of influenza.

Effects of School-Based Preventive Measures on COVID-19 Incidence, Hong Kong, 2022.

We show that school closures reduced COVID-19 incidence rates in children by 31%-46% in Hong Kong in 2022. After school reopening accompanied by mask mandates, daily rapid testing, and vaccination requirements, school-reported cases correlated with community incidence rates. Safe school reopening is possible when appropriate preventive measures are used.

Revisiting assumptions in test-negative studies for estimating vaccine effectiveness: the need for a clinical case definition.

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all group consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong.

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (Re) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.

The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households.

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases including SARS-CoV-2. However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2- to 4.2-fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

Impact of host genetic polymorphisms on response to inactivated influenza vaccine in children.

In randomized controlled trials of influenza vaccination, 550 children received trivalent-inactivated influenza vaccine, permitting us to explore relationship between vaccine response and host single nucleotide polymorphisms (SNPs) in 23 candidate genes with adjustment of multiple testing. For host SNPs in TLR7-1817G/T (rs5741880), genotype GT was associated with lower odds (OR: 0.22, 95% CI: 0.09, 0.53) of have post-vaccination hemagglutination-inhibiting (HAI) titers ≥40, compared with genotype GG and TT combined under the over-dominant model. For host SNPs in TLR8-129G/C (rs3764879), genotype GT was associated with lower odds (OR: 0.47; 95% CI: 0.28, 0.80) of have post vaccination HAI titers ≥40 compared with genotype GG and AA combined under the over-dominant model. Our results could contribute to the development of better vaccines that may offer improved protection to all recipients.

Accounting for the Potential of Overdispersion in Estimation of the Time-varying Reproduction Number.

BACKGROUND: The time-varying reproduction number, Rt, is commonly used to monitor the transmissibility of an infectious disease during an epidemic, but standard methods for estimating Rt seldom account for the impact of overdispersion on transmission. METHODS: We developed a negative binomial framework to estimate Rt and a time-varying dispersion parameter (kt). We applied the framework to COVID-19 incidence data in Hong Kong in 2020 and 2021. We conducted a simulation study to compare the performance of our model with the conventional Poisson-based approach. RESULTS: Our framework estimated an Rt peaking around 4 (95% credible interval = 3.13, 4.30), similar to that from the Poisson approach but with a better model fit. Our approach further estimated kt <0.5 at the start of both waves, indicating appreciable heterogeneity in transmission. We also found that kt decreased sharply to around 0.4 when a large cluster of infections occurred. CONCLUSIONS: Our proposed approach can contribute to the estimation of Rt and monitoring of the time-varying dispersion parameters to quantify the role of superspreading.

Characterizing Human Collective Behaviors During COVID-19 - Hong Kong SAR, China, 2020.

What is already known about this topic?: People are likely to engage in collective behaviors online during extreme events, such as the coronavirus disease 2019 (COVID-19) crisis, to express awareness, take action, and work through concerns. What is added by this report?: This study offers a framework for evaluating interactions among individuals' emotions, perceptions, and online behaviors in Hong Kong Special Administrative Region (SAR) during the first two waves of COVID-19 (February to June 2020). Its results indicate a strong correlation between online behaviors, such as Google searches, and the real-time reproduction numbers. To validate the model's output of risk perception, this investigation conducted 10 rounds of cross-sectional telephone surveys on 8,593 local adult residents from February 1 through June 20 in 2020 to quantify risk perception levels over time. What are the implications for public health practice?: Compared to the survey results, the estimates of the risk perception of individuals using our network-based mechanistic model capture 80% of the trend of people's risk perception (individuals who are worried about being infected) during the studied period. We may need to reinvigorate the public by involving people as part of the solution that reduced the risk to their lives.

Epidemiology of SARS-CoV-2 Omicron BA.5 Infections, Macau, June-July 2022.

A SARS-CoV-2 Omicron BA.5 outbreak occurred in Macau from mid-June through July 2022. Out of >1,800 laboratory-confirmed cases, most were mild or asymptomatic; only 6 deaths were recorded. The outbreak was controlled through stringent public health and social measures, such as repeated universal testing and a stay-at-home order lasting 2 weeks.