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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.

The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters.OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis.A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P0.03) reduced the elevated false positive rates.Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias.Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Summary Background Since the emergence of the COVID-19 pandemic in late 2019, various public health and social measures (PHSMs) have been used to suppress and mitigate the spread of SARS-CoV-2. With mass vaccination programmes against COVID-19 being rolled out in many countries in early 2021, we aimed to evaluate to what extent travel restrictions and other PHSMs can be relaxed without exacerbating the local and global spread of COVID-19. Methods We adapted an existing age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics that can be parameterised with country-specific age demographics and contact patterns to simulate the effect of vaccination and PHSM relaxation on transmission. We varied assumptions by age-specific susceptibility and infectiousness, vaccine uptake, contact patterns, and age structures. We used Hong Kong as a case study and assumed that, before vaccination, the population is completely susceptible to SARS-CoV-2 infection. We applied our model to 304 jurisdictions (27 countries and 277 sub-national administrative regions from eight countries). We assumed that PHSMs have suppressed the effective reproductive number (Re) to fall between 1·0 and 9·0 locally before the commencement of vaccination programmes. We evaluated the levels of PHSMs that should be maintained during the roll-out of COVID-19 vaccination to avoid a large local outbreak of COVID-19, with different assumptions about vaccine efficacy, vaccination coverage, and travel restrictions. We assumed that the maximum capacity of the health system, in terms of daily hospital admissions, is 0·005% of the population size. Findings At vaccine efficacy of 0·80 in reducing susceptibility to SARS-CoV-2 infection, 0·50 in reducing SARS-CoV-2 infectivity, and 0·95 in reducing symptomatic COVID-19 diseases, vaccination coverage would have to be 100% for all individuals aged 30 or older to avoid an outbreak, when relaxing PHSMs, that would overload the local health-care system, assuming a pre-vaccination Re of 2·5. Testing and quarantine of at least 5 days would have to be maintained for inbound travellers to minimise the risk of reintroducing a local outbreak until high vaccination coverages are attained locally and overseas in most countries. Interpretation Gradual relaxation of PHSMs should be carefully planned during the roll-out of vaccination programmes, and easing of travel restrictions weighed against risk of reintroducing outbreaks, to avoid overwhelming health systems and minimise deaths related to COVID-19. Funding Health and Medical Research Fund and the General Research Fund.

Summary Objectives mask-wearing outside the home has been almost universal in Hong Kong since late January 2020 with very high compliance. Nevertheless, community spread of COVID-19 has still occurred. We aimed to assess the settings where COVID-19 transmission occurred and determine the fraction of transmission events that occurred in settings where masks are not usually worn. Methods we reviewed detailed information provided by the Hong Kong Department of Health on local COVID-19 cases diagnosed up to 30 September 2020 to determine the most likely settings in which transmission occurred. We classified them in probably mask-on or mask-of and compared the prevalence of asymptomatic infections in these settings. Results among the 2425 cases (65.3%, 2425/3711) with information on transmission setting, 77.6% of the transmission occurred in household and social settings where face masks are not usually worn. Infections that occurred in mask-on settings were more likely to be asymptomatic (adjusted odds ratio 1.33; 95% confidence interval: 1.04, 1.68). Conclusions we conclude that universal mask-wearing can reduce transmission, but transmission can continue to occur in settings where face masks are not usually worn. The higher proportion of asymptomatic cases in mask-on settings could be related to a milder disease presentation or earlier case detection.

BackgroundThere are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines.MethodsWe conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up.ResultsWe enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac (“CC-C”, n=101) or BNT162b2 (“CC-B”, n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac (“BB-C”, n=118) or BNT162b2 (“BB-B”, n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56).ConclusionsSimilar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

BackgroundHong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures.MethodsWe conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values.ResultsThere were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; pConclusionsTesting inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood samples before the third dose and again after one month and six months, and found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by six months.

IntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses.MethodsWe administered BNT162b2 as a third dose to adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2.ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity.ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.

BackgroundOn-arrival quarantine has been one of the primary measures used to prevent the introduction of COVID-19 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine varying throughout the pandemic for various reasons. However, hotels are not necessarily designed with infection control in mind. We aimed to study the potential risk of transmission between persons in on-arrival quarantine.MethodsWe examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the full genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. A combination of epidemiological information and sequence information was then used to identify probable transmission events.FindingsAmong 221 imported cases that overlapped with other quarantined cases, phylogenetic analysis identified eight suspected clusters comprising 20 cases in total. Only three of these clusters had been recognised as hotel transmission events.InterpretationWe have identified potential occurrences of COVID-19 transmission within hotel quarantine in Hong Kong demonstrating the underlying low but non-zero risk associated with sequestering arrivals within hotels. In future pandemics, on-arrival quarantine in hotels could be used to delay the introduction of infection, but the construction of purpose-built facilities for on-arrival quarantine might be necessary to minimize importation risk.FundingHealth and Medical Research Fund, Hong Kong

International audience

Epidemic nowcasting broadly refers to assessing the current state by understanding key pathogenic, epidemiologic, clinical and socio-behavioral characteristics of an ongoing outbreak. Its primary objective is to provide situational awareness and inform decisions on control responses. In the event of large-scale sustained emergencies, such as the COVID-19 pandemic, scientists need to constantly update their aims and analytics with respect to the rapidly evolving emergence of new questions, data and findings in order to synthesize real-time evidence for policy decisions. In this Perspective, we share our views on the functional aims, rationale, data requirements and challenges of nowcasting at different stages of an epidemic, drawing on the ongoing COVID-19 experience. We highlight how recent advances in the computational and laboratory sciences could be harnessed to complement traditional approaches to enhance the scope, timeliness, reliability and utility of epidemic nowcasting.

BackgroundEvidence evaluating real-world effectiveness of oral antivirals against Omicron variants is lacking.MethodsAn unselected, territory-wide cohort of all initially non-hospitalized patients with an officially registered diagnosis of SARS-CoV-2 infection between 26th February and 3rd May 2022 during the Omicron BA.2.2 wave in Hong Kong, was identified. We undertook a retrospective cohort design as primary analysis, and case-control design as sensitivity analysis. Outpatient oral antiviral users were matched with controls using 1:10 propensity-score matching. Study outcomes were mortality, COVID-19-related hospitalization, composite outcome of in-hospital disease progression (in-hospital mortality, invasive mechanical ventilation, or intensive care unit admission) and its individual outcomes. Hazard ratios (HR) were estimated by Cox regression, and odds ratios in oral antiviral users compared with non-users by logistic regression. Subgroup analyses evaluated the associations by vaccination status and age.FindingsAmong 1,072,004 non-hospitalized COVID-19 patients, 5,257 and 5,663 were initiated molnupiravir and nirmatrelvir/ritonavir in the community setting with a median follow-up of 42 and 38 days, respectively. Molnupiravir use was associated with lower risks of mortality (HR=0·61, 95%CI=0·46-0·82, pInterpretationAmid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir.FundingHealth and Medical Research Fund, Food and Health BureauResearch in contextEvidence before this studyOral antivirals have been initiating in non-hospitalized COVID-19 patients to lower their risks of hospitalization and death, and hence to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 25 May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the outpatient use of molnupiravir and nirmatrelvir/ritonavir are MOVe-OUT and EPIC-HR trials, respectively. Both have been conducted among unvaccinated, non-hospitalized patients with mild-to-moderate COVID-19 who are at risk of progression to severe disease, during a pandemic wave of SARS-CoV-2 Delta variant. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Considering the real-world evaluation of the two oral antivirals against the currently circulating Omicron variant, only one single-center, retrospective review of solid organ transplant recipients with COVID-19 has been conducted; yet their results are unlikely generalizable to other populations given its specific patient group and small sample size. Real-world effectiveness of oral antivirals is urgently needed to inform their clinical use in COVID-19 patients, considering their vaccination status and the variant of concern.Added value of this studyTo the best of our knowledge, this is one of the first real-world studies exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. A territory-wide, retrospective cohort study was conducted to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in community-dwelling COVID-19 patients. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset was associated with significant reduction of all-cause mortality risk by 39% and 75%, respectively, compared to not using any oral antivirals. Nirmatrelvir/ritonavir use was also associated with a reduced risk of COVID-19-related hospitalization by 31%, which was consistently observed across age and vaccination status. In terms of disease progression, both oral antivirals were effective in lowering the risk of in-hospital death, which was again more substantial with nirmatrelvir/ritonavir than molnupiravir. Intriguingly, the need for invasive ventilation might be reduced among molnupiravir users compared to matched controls.Implications of all the available evidenceBased on relative efficacy, our findings give support to current guidelines prioritizing nirmatrelvir/ritonavir use over molnupiravir in community-dwelling COVID-19 patients who are at high risk of hospitalization or progression to severe disease, should the former be accessible and clinically appropriate. Amid a pandemic wave of the Omicron variant, real-world effectiveness of oral antivirals in reducing the mortality risk of community-dwelling COVID-19 patients has been demonstrated in this study consisting mostly of the elderly and those who had not been fully vaccinated, extending beyond the evidence demonstrated in clinical trials among those of the Delta variant and who were at risk of severe COVID-19 from being overweight/obese. Several clinical trials (namely RECOVERY and PANORAMIC) and observational studies of the two oral antivirals are ongoing, and further research is needed to confirm our results in other patient populations and healthcare settings.

Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong.In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30-59 mL/min per 1·73 mAmong 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61-0·95]) and in-hospital disease progression (0·57 [0·43-0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89-1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22-0·52]), hospitalisation (0·76 [0·67-0·86]), and in-hospital disease progression (0·57 [0·38-0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis.During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation.Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China.For the Chinese translation of the abstract see Supplementary Materials section.

SummaryBackgroundEffectiveness of oral antivirals in mild-to-moderate COVID-19 patients is urgently needed. This retrospective cohort study aims to evaluate the clinical and virologic outcomes associated with molnupiravir and nirmatrelvir/ritonavir use in COVID-19 patients during a pandemic wave dominated by the Omicron BA.2 subvariant.MethodsWe analyzed data from a territory-wide retrospective cohort of hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection from 26th February 2022 to 26th April 2022 in Hong Kong. Oral antiviral users were matched with controls using propensity-score matching in a ratio of 1:1. Study outcomes were all-cause mortality, a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit admission, or the need for oxygen therapy) and their individual outcomes, and time to achieving lower viral burden of cycle threshold (Ct) value ≥30 cycles. Hazard ratios (HR) of event outcomes were estimated using Cox regression models.ResultsAmong 40,776 hospitalized patients with SARS-CoV-2 infection over a mean follow-up of 41.3 days with 925,713 person-days, this study included 1,856 molnupiravir users, 890 nirmatrelvir/ritonavir users and 2,746 control patients not initially requiring oxygen therapy at baseline after propensity-score matching. Oral antiviral use was associated with significantly lower risks of all-cause mortality (molnupiravir: HR=0.48, 95%CI=0.40-0.59, pConclusionsAgainst Omicron BA.2, initiation of novel oral antiviral treatment in hospitalized patients not requiring any oxygen therapy was associated with lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster. Our findings support the early use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission.FundingHealth and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong SARResearch in contextEvidence before this studyThe medical and research community are actively exploring the use of oral antivirals in COVID-19 patients to lower their risks of hospitalization and death, and to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 13th May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the safety and efficacy of molnupiravir include MOVe-IN and MOVe-OUT trials conducted in hospitalized and non-hospitalized COVID-19 patients, respectively. Clinical evidence for the use of ritonavir-boosted nirmatrelvir came from the EPIC-HR trial conducted among non-hospitalized adults with COVID-19. While no clinical benefits have been observed with molnupiravir use in the inpatient setting among patients with moderate-to-severe COVID-19, early initiation of molnupiravir or nirmatrelvir/ritonavir within 5 days of symptom onset in non-hospitalized patients with mild-to-moderate COVID-19 and risk factors for progression to severe disease has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Notably, these clinical trials were conducted prior to the prevalence of Omicron variant, and the efficacy of oral antivirals against this current variant of concern can only be inferred from experimental evidence to date. Real-world evidence of oral antiviral use in patients with SARS-CoV-2 infection of Omicron variant is lacking.Added value of this studyTo the best of our knowledge, this is the first real-world study exploring the inpatient use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. We conducted a territory-wide, retrospective cohort study to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in COVID-19 patients who did not require supplemental oxygen on admission in Hong Kong. Early initiation of oral antivirals within 2 days of admission was associated with significantly lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster than their respective matched controls. Oral antiviral use was also associated with a reduced need for oxygen therapy than non-use.Implications of all the available evidenceCurrent guidelines are now prioritizing the distribution of oral antivirals to those who do not require supplemental oxygen, but who are at the highest risk of disease progression. Our study cohort reflected such prescription pattern in real-world clinical practice, consisting of mostly the elderly with multiple pre-existing comorbidities and who had not been fully vaccinated. The antiviral effect and mortality benefit observed in this patient cohort support the use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission during a pandemic wave of Omicron variant. Ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations (by vaccination status and viral variants), drug combinations, and different healthcare settings.

Sewage surveillance, by detecting SARS-CoV-2 virus circulation at the community level, has the potential to supplement individual surveillance for COVID-19. However, to date, there have been no reports about the large-scale implementation and validation of sewage surveillance for public health action.Here, we developed a standardized approach for SARS-CoV-2 detection in sewage and applied it prospectively to supplement public health interventions.We analyzed 1,169 sewage samples collected at 492 sites from December 2020 to March 2021. Forty-seven of 492 sites tested positive, 44 (94%) of them had traceable sources of viral signals in the corresponding sewershed, either from previously unsuspected but subsequently confirmed patients or recently convalescent patients or from both patient groups.Sewage surveillance had a sensitivity of 54%, a specificity of 95%, a positive predictive value of 53%, and a negative predictive value of 95% for identifying a previously unsuspected patient within a sewershed. Sewage surveillance in Hong Kong provided a basis for the statutory public health action to detect silent COVID-19 transmission.Considering the epidemiological data together with the sewage testing results, compulsory testing was conducted for individual residents at 27 positive sewage sites and uncovered total of 62 previously unsuspected patients, demonstrating the value of sewage surveillance in uncovering previously unsuspected patients in the community. Our study suggests that sewage surveillance could be a powerful management tool for the control of COVID-19. https://doi.org/10.1289/EHP9966.

Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths. Our data indicated a shorter incubation period, serial interval, and generation time of infections with Omicron than other SARS-CoV-2 variants. Omicron BA.2.2 cases without a complete primary vaccination series appeared to face a similar fatality risk to those infected in earlier waves with the ancestral strain.

BackgroundHong Kong maintained extremely low circulation of SARS-CoV-2 until a major community epidemic of Omicron BA.2 starting in January 2022. Both mRNA BNT162b2 (BioNTech/Fosun Pharma) and inactivated CoronaVac (Sinovac) vaccines are widely available, however coverage has remained low in older adults. Vaccine effectiveness in this predominantly infection-naïve population is unknown.MethodsWe used individual-level case data on mild/moderate, severe/fatal and fatal hospitalized COVID-19 from December 31, 2021 to March 8, 2022, along with census information and coverage data of BNT162b2 and CoronaVac. We used a negative binomial model, adjusting for age and calendar day to estimate vaccine effectiveness of one, two and three dose schedules of both vaccines, and relative effectiveness by number of doses and vaccine type.FindingsA total of 12.7 million vaccine doses were administered in Hong Kong’s 7.3 million population, and we analyzed data from confirmed cases with mild/moderate (N=5,474), severe/fatal (N=5,294) and fatal (N=4,093) COVID-19. Two doses of either vaccine protected against severe disease and death, with higher effectiveness among adults ≥60 years with BNT162b2 (VE: 88.2%, 95% confidence interval, CI: 84.4%, 91.1%) compared to CoronaVac (VE: 74.1%, 95% CI: 67.8%, 79.2%). Three doses of either vaccine offered very high levels of protection against severe outcomes (VE: 98.1%, 95% CI: 97.1%, 98.8%).InterpretationThird doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19 and should be prioritized, particularly in older adults who received CoronaVac primary schedules. Longer follow-up is needed to assess persistence of different vaccine platforms and schedules.FundingCOVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We compared rates of antibody waning over time using an enzyme-linked immunosorbent assay for spike receptor binding domain and a surrogate virus neutralization test. We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women. The weaker and less durable responses following CoronaVac support earlier provision of third doses to persons who previously received two doses of this vaccine.

COVID-19 vaccines are important tools to protect populations from severe disease and death.Among persons aged ≥60 years in Hong Kong, 49%, had received ≥2 doses of a COVID-19 vaccine, and vaccination coverage declined with age. During January-March 2022, reported COVID-19-associated deaths rose rapidly in Hong Kong. Among these deaths, 96% occurred in persons aged ≥60 years; within this age group, the risk for death was 20 times lower among those who were fully vaccinated compared with those who were unvaccinated.Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially in older adults.

Aim Angiotensin-converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARSCoV-2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy. Methods We used a Mendelian randomization study to obtain unconfounded associations of antihypertensives, instrumented by published genetic variants in genes regulating target proteins of these drugs, with immune (lymphocyte and neutrophil percentage) and inflammatory (tumour necrosis factor alpha [TNF-α]) markers in the largest available genome-wide association studies. Results Genetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (-0.64, 95% CI -1.09, -0.20) and possibly lowered TNF-α (-4.92, 95% CI -8.50, -1.33). CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage -0.23, 95% CI -0.39 to -0.08) but had no effect on TNF-α, as did potassium-sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives. ARBs and other classes of hypertensives had no effect on immune function or TNF-α. Conclusion Varying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV-2.

Background Owing to rapidly raising property prices, living with parents is the most common living arrangement among young adults in urban areas. Studies for “full nest syndrome” or “boomerang children” have demonstrated that moving back in with parents was associated with more depressive symptoms. On the other hand, studies have suggested that living with parents was not associated with mental health in several countries where inter-generational households could potentially provide more social support among household members. We examined whether delayed residential independence might adversely impact mental health of young adults. Methods The cross-sectional study was conducted from 2009 to 2011 in Hong Kong SAR, China – a highly urbanized city with the least affordable housing in the world. The analytic samples were 3612 young adults. Outcomes of interest were depressive symptoms and mental well-being. Results Co-residence with parents under self headship was associated with young adults’ fewer depressive symptoms (β = -0.157, 95% confidence interval [CI] = -0.311 to -0.003) and better mental well-being (β = 1.342, 95% CI = 0.522 to 2.162). Limitations This is susceptible to reverse causation, whereby young adults with poorer mental health may be more likely to stay or move back into their parental home. Conclusions Our findings showed that young adults co-residing with parents as the household head were associated with fewer depressive symptoms and better mental well-being compared to living with parents under their parental headship.

Improvements in medical treatment have contributed to rising health spending. Yet there is relatively little evidence on whether the spending increase is “worth it” in the sense of producing better health outcomes of commensurate value—a critical question for understanding productivity in the health sector and, as that sector grows, for deriving an accurate quality-adjusted price index for an entire economy. We analyze individual-level panel data on medical spending and health outcomes for 123,548 patients with type 2 diabetes in four health systems: Japan, The Netherlands, Hong Kong and Taiwan. Using a “cost-of-living” method that measures value based on improved survival, we find a positive net value of diabetes care: the value of improved survival outweighs the added costs of care in each of the four health systems. This finding is robust to accounting for selective survival, end-of-life spending, and a range of values for a life-year or fraction of benefits attributable to medical care. Since the estimates do not include the value from improved quality of life, they are conservative. We, therefore, conclude that the increase in medical spending for management of diabetes is offset by an increase in quality.

To investigate the prevalence, associations, and causes of visual impairment and blindness in the adult population of Hong Kong.This cross-sectional population-based study included 2018 (870, 43% male) randomly selected adults with a mean age 52 ± 16 years (range 18-90 years) in Hong Kong. Each participant underwent comprehensive ophthalmic examinations. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) of each eye was recorded. Prevalence of visual impairment and blindness was calculated using both World Health Organization (WHO) and United States (US) definitions, based on BCVA and PVA.Visual acuity measurements were available for 1952 (96.8%) participants. The prevalence of visual impairment, based on BCVA value, using WHO and US definition, was 1.0 ± 0.1% and 2.7 ± 0.4%, respectively. The prevalence of visual impairment, based on PVA value, was 5.1 ± 0.5% and 14.0 ± 0.8%, using WHO and US definition, respectively. Multivariate analysis demonstrated the presence of visual impairment (PVA, WHO definition) increased significantly with older age (odds ratio 1.039,The prevalence of visual impairment in Hong Kong increased significantly with older age and thinner central corneal thickness. The major causes for impairment were under-correction of refractive error, cataract, and age-related macular degeneration.

We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)

As of 29 February 2020 there were 79,394 confirmed cases and 2,838 deaths from COVID-19 in mainland China. Of these, 48,557 cases and 2,169 deaths occurred in the epicenter, Wuhan. A key public health priority during the emergence of a novel pathogen is estimating clinical severity, which requires properly adjusting for the case ascertainment rate and the delay between symptoms onset and death. Using public and published information, we estimate that the overall symptomatic case fatality risk (the probability of dying after developing symptoms) of COVID-19 in Wuhan was 1.4% (0.9–2.1%), which is substantially lower than both the corresponding crude or naive confirmed case fatality risk (2,169/48,557 = 4.5%) and the approximator1 of deaths/deaths + recoveries (2,169/2,169 + 17,572 = 11%) as of 29 February 2020. Compared to those aged 30–59 years, those aged below 30 and above 59 years were 0.6 (0.3–1.1) and 5.1 (4.2–6.1) times more likely to die after developing symptoms. The risk of symptomatic infection increased with age (for example, at ~4% per year among adults aged 30–60 years). An estimation of the clinical severity of COVID-19, based on the data available so far, can help to inform the public health response during the ongoing SARS-CoV-2 pandemic.

Summary Background Hong Kong has been embroiled in increasingly violent social unrest since June, 2019. We examined the associated population mental health burden, risk factors, and health-care needs. Methods In a population-based prospective cohort, adult participants aged 18 years or older were assessed at nine timepoints from 2009. Probable depression was measured using the Patient Health Questionnaire-9 (score ≥10) and suspected post-traumatic stress disorder (PTSD) by the PTSD Checklist—Civilian Version (score ≥14), plus direct exposure to traumatic events related to the ongoing social unrest. We used multivariable logistic regression to identify factors associated with both outcomes, adjusting for doctor-diagnosed depression or anxiety disorders before the unrest. On the basis of routine service statistics and respondents' intention to seek professional care, we projected the number of additional ambulatory specialist psychiatric visits required. Findings After the two baseline surveys, we followed up random subsets of 1213–1736 adults at each timepoint. Probable depression was reported by 11·2% (95% CI 9·8–12·7) of participants in 2019, compared with 1·9% (1·6–2·1) during 2009–14 and 6·5% (5·3–7·6) in 2017 after the Occupy Central Movement and before the current unrest. Prevalence of suspected PTSD in 2019 was estimated to be 12·8% (11·2–14·4). Age, sex, educational attainment, or household income were not associated with either outcome, whereas heavy social media use (≥2 h per day) was associated with both. Political attitude or protest participation was not associated with probable depression, but neutrality towards the extradition bill approximately halved the risk of suspected PTSD. Family support mitigated against probable depression. We estimated that the mental health burden identified would translate into roughly an excess 12% service requirement to the public sector queue or equivalent. Interpretation We have identified a major mental health burden during the social unrest in Hong Kong, which will require substantial increases in service surge capacity. Health-care and social care professionals should be vigilant in recognising possible mental health sequelae. In a world of increasing unrest, our findings might have implications for service planning to better protect population mental health globally. Funding Research Grants Council, University Grants Committee of Hong Kong, Hong Kong Jockey Club Charities Trust.

Background Rapid growth is related to adverse respiratory outcomes although possibly confounded or limited by growth modelling methods. We investigated the association of infant and pubertal growth with lung function, wheezing and asthma in a non-Western setting. Methods In Hong Kong’s ‘Children of 1997’ Chinese birth cohort (n = 8327), weight during infancy and weight, height and body mass index (BMI) during puberty were modelled using a super-imposition by translation and rotation model to identify (larger or smaller) size, (earlier or later) tempo and (slower or faster) velocity. Sex-specific associations with forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC (Global Lung function Initiative z-score) and self-reported wheezing and asthma at ∼17.5 years were assessed. Results For each fraction higher than average weight growth velocity during infancy, FVC was higher in boys (0.90 SD, 95% CI 0.35; 1.44) and girls (0.77 SD, 95% CI 0.24; 1.30), FEV1/FVC was lower (–0.74 SD, 95% CI –1.38; –0.10) and wheezing was higher (odds ratio 6.92, 95% CI 1.60; 29.99) in boys and an inverse association with FVC was observed for tempo but not for size. Associations for weight growth velocity in puberty were similar but weaker. Greater size and higher velocity of BMI growth was associated with higher FVC, lower FEV1/FVC and higher asthma and wheezing risk. Conclusion Accelerated infant and pubertal weight growth were associated with disproportionate lung size and airway growth, and higher risk of asthma; optimizing early-life growth patterns could be important.

Limited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants.We conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT.In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p 0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p 0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by 45 fold from Day 0 to Day 28 against the ancestral virus (p 0.001) and rose by 11 fold against the Omicron variant (p 0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants.A third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.

This study aims to provide evidence on how the COVID-19 pandemic has impacted chronic disease care in diverse settings across Asia. Cross-sectional surveys were conducted to assess the health, social, and economic consequences of the pandemic in India, China, Hong Kong, Korea, and Vietnam using standardized questionnaires. Overall, 5672 participants with chronic conditions were recruited from five countries. The mean age of the participants ranged from 55.9 to 69.3 years. A worsened economic status during the COVID-19 pandemic was reported by 19% to 59% of the study participants. Increased difficulty in accessing care was reported by 8% to 24% of participants, except Vietnam: 1.6%. The worsening of diabetes symptoms was reported by 5.6% to 14.6% of participants, except Vietnam: 3%. In multivariable regression analyses, increasing age, female participants, and worsened economic status were suggestive of increased difficulty in access to care, but these associations mostly did not reach statistical significance. In India and China, rural residence, worsened economic status and self-reported hypertension were statistically significantly associated with increased difficulty in access to care or worsening of diabetes symptoms. These findings suggest that the pandemic disproportionately affected marginalized and rural populations in Asia, negatively affecting population health beyond those directly suffering from COVID-19.

BackgroundLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants.MethodsWe conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT.ResultsIn 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p50 titers rose very substantially by at least 24 fold from Day 0 to Day 28 against the ancestral virus (pConclusionsA third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.SummaryIn this open label trial of Chinese adults aged ≥30 years who received two doses of inactivated COVID-19 vaccine 6 months earlier, third-dose mRNA vaccine substantially improved antibody levels against the ancestral virus and Omicron variant with well-tolerated safety profile.

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number “Rt”, a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections.One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.

Introduction The SARS-CoV-2 lineages carrying the amino acid change D614G have become the dominant variants in the global COVID-19 pandemic. By June 2021, all the emerging variants of concern carried the D614G mutation. The rapid spread of the G614 mutant suggests that it may have a transmission advantage over the D614 wildtype. Aim Our objective was to estimate the transmission advantage of D614G by integrating phylogenetic and epidemiological analysis. Methods We assume that the mutation D614G was the only site of interest which characterised the two cocirculating virus strains by June 2020, but their differential transmissibility might be attributable to a combination of D614G and other mutations. We define the fitness of G614 as the ratio of the basic reproduction number of the strain with G614 to the strain with D614 and applied an epidemiological framework for fitness inference to analyse SARS-CoV-2 surveillance and sequence data. Results Using this framework, we estimated that the G614 mutant is 31% (95% credible interval: 28–34) more transmissible than the D614 wildtype. Therefore, interventions that were previously effective in containing or mitigating the D614 wildtype (e.g. in China, Vietnam and Thailand) may be less effective against the G614 mutant. Conclusion Our framework can be readily integrated into current SARS-CoV-2 surveillance to monitor the emergence and fitness of mutant strains such that pandemic surveillance, disease control and development of treatment and vaccines can be adjusted dynamically.

ObjectivesThis study aims to explore the attenuated impact of reported avoidance behaviours adherence on the transmission of COVID-19 through cross-sectional surveys in Hong Kong, in order to make up for the lack of research on avoidance behaviours fatigue.Design40 cross-sectional telephone surveys.SettingAll districts in Hong Kong.Participants31 332 Cantonese or English-speaking participants at age of 18 years or above.MethodsWe collected data on behaviours and estimated the average effective reproduction number (Rt) among the Hong Kong adult population during the COVID-19 epidemic wave in November–December 2020 and compared with the preceding epidemic in June–July 2020.ResultsWe observed a reduction in adherence to voluntary avoidance behaviours due to pandemic fatigue, but continued adherence to regulated avoidance behaviours. The average Rt during the post-work from home period was higher in November–December wave with estimated Rt of 0.81 (95% CI: 0.75 to 0.87) compared with the June–July wave with an Rt of 0.67 (95% CI: 0.60 to 0.75).ConclusionsThe declined effectiveness of social distancing interventions in reducing COVID-19 transmission was associated with fatigue with voluntary avoidance behaviours in Hong Kong population, implying a need for the government to reinvigorate the public to maintain effective pandemic control.