Pragmatic multicentre stepped-wedge cluster randomised trial to investigate the effectiveness of community-based falls prevention programme for older adults with falls risk in Singapore: a protocol paper.

INTRODUCTION: Falls are an important public health issue with consequences that include injuries, quality of life reduction and high healthcare costs. Studies show that falls prevention strategies are effective in reducing falls rate among community-dwelling older adults. However, the evaluation for effectiveness was usually done in a controlled setting with homogeneous population, and thus may not be generalisable to a wider population. This study aims to evaluate the impact of community falls prevention programmes with group-based strength and balance exercises, on falls risk and health outcomes for older adults with falls risk in Singapore. METHODS AND ANALYSIS: This is a pragmatic closed cohort stepped-wedge cluster randomised trial design study, which involves sequential crossover of clusters from the waitlist control condition to the intervention condition, with the sequence of crossover randomly determined. The intervention will be sequentially rolled out to 12 clusters (a minimum of 5 participants/cluster), over 6 time periods with 8-week intervals in Central and North regions of Singapore. The primary analysis will be conducted under the intention-to-treat principle. A general linear mixed model or generalised estimating equation analysis appropriate for a multilevel longitudinal study incorporating an appropriate error distribution and link function will be used. Markov model will be developed to estimate the incremental cost per quality-adjusted life years and incremental cost per fall prevented from the implementation of falls prevention strategies from a societal perspective. Conditional on there being clinically relevant differences in short-term outcomes, we will implement simulation modelling to project the long-term divergence in trajectories for outcomes and costs using the Markov model. ETHICS AND DISSEMINATION: Ethics approval has been obtained. Results will be disseminated in publications and other relevant platforms. TRIAL REGISTRATION NUMBER: NCT04788251.

Second-hand smoke and fine particulate matter exposures among multi-unit housing residents in Singapore: A pilot study.

Globally, approximately 1.2 million deaths among non-smokers are attributed to second-hand smoke (SHS) per year. Multi-unit housing is becoming the common type of residential dwelling in developed cities and the issue of neighbour SHS is of rising concern especially as 'Work From Home' became the norm during and post COVID-19 pandemic. The objective of this pilot study is to measure and compare the air quality of households that are exposed to SHS and unexposed households among smoking and non-smoking households in Singapore. A total of 27 households were recruited from April to August 2021. Households were categorized into smoking households with neighbour SHS, smoking households without neighbour SHS, non-smoking households with neighbour SHS, and non-smoking household without neighbour SHS. Air quality of the households was measured using calibrated particulate matter (PM2.5) sensors for 7-16 days. Socio-demographic information and self-reported respiratory health were collected. Regression models were used to identify predictors associated with household PM2.5 concentrations and respiratory health. Mean PM2.5 concentration was significantly higher among non-smoking households with neighbour SHS (n = 5, mean = 22.2, IQR = 12.7) than in non-smoking household without neighbour SHS (n = 2, mean = 4.1, IQR = 5.8). Smoking activity at enclosed areas in homes had the lowest PM2.5 concentration (n = 7 mean = 15.9, IQR = 11.0) among the three smoking locations. Exposure to higher household PM2.5 concentration was found to be associated with poorer respiratory health. A 'smoke-free residential building' policy is recommended to tackle the issue of rising neighbour SHS complaints and health concerns in densely populated multi-unit housing in Singapore. Public education campaigns should encourage smokers to smoke away from the home to minimize SHS exposure in household members.

BNT162b2 vaccine protection against omicron and effect of previous infection variant and vaccination sequence among children and adolescents in Singapore: a population-based cohort study.

BACKGROUND: Information on variant-specific vaccine protection and the effect of previous infection variant is scarce in children. We aimed to ascertain the level of protection conferred by BNT162b2 COVID-19 vaccination against omicron variant infection (BA.4 or BA.5, and XBB) in a previously infected national paediatric cohort. We also explored the association between sequence of previous infection (variant) and vaccination on protection. METHODS: We did a retrospective, population-based cohort study using the national databases of all confirmed SARS-CoV-2 infections, vaccines administered, and demographic records maintained by the Ministry of Health, Singapore. The study cohort consisted of children aged 5-11 years and adolescents aged 12-17 years who had a previous SARS-CoV-2 infection from Jan 1, 2020, to Dec 15, 2022. People who were infected during the pre-delta period or were immunocompromised (received three vaccination doses [children 5-11 years old] and four vaccinations doses [adolescents 12-17 years old]) were excluded. Those who had multiple episodes of infection before the study start date, were not vaccinated before infection but completed three doses, received bivalent mRNA vaccine, or received non-mRNA vaccine doses were also excluded. All SARS-CoV-2 infections confirmed by reverse transcriptase polymerase chain reaction or rapid antigen testing were grouped into delta, BA.1, BA.2, BA.4 or BA.5, or XBB variants using a combination of whole-genome sequencing, S-gene target failure results, and imputation. For BA.4 or BA.5, the study outcome period was June 1-Sept 30, 2022, and for XBB variants the outcome period was Oct 18-Dec 15, 2022. Incidence rate ratios between vaccinated and unvaccinated were derived using adjusted Poisson regressions and vaccine effectiveness was estimated as (1-risk ratio) × 100%. FINDINGS: 135 197 people aged 5-17 years (79 332 children and 55 865 adolescents) were included in the cohort for the vaccine effectiveness analysis against omicron BA.4 or BA.5, and 164 704 people aged 5-17 years (97 235 children and 67 469 adolescents) were included for the analysis against omicron XBB. Approximately 47% of participants were female and 53% were male. Among those previously infected, vaccine effectiveness against BA.4 or BA.5 infection in fully vaccinated children (two doses) was 74·0% (95% CI 67·7-79·1) and in adolescents (three doses) was 85·7% (80·2-89·6). Against XBB, protection conferred with full vaccination was lower at 62·8% (95% CI 42·3-76·0) in children and 47·9% (20·2-66·1) in adolescents. In children, receipt of two-dose vaccination before first SARS-CoV-2 infection provided them with the highest protection against subsequent BA.4 or BA.5 infection at 85·3% (95% CI 80·2-89·1); however, this was not shown to be the case for adolescents. First infection variant had an effect on vaccine effectiveness against omicron BA.4 or BA.5 reinfection in the following descending order: BA.2 conferred the highest protection (92·3% [95% CI 88·9-94·7] in children and 96·4% [93·5-98·0] in adolescents) followed by BA.1 (81·9% [75·9-86·4] in children and 95·0% [91·6-97·0] in adolescents), and delta which conferred the lowest protection (51·9% [5·3-75·6] in children and 77·5% [63·9-86·0] in adolescents). INTERPRETATION: In previously infected children and adolescents, BNT162b2 vaccination provided additional protection against omicron BA.4 or BA.5 and XBB variants compared with those who remained unvaccinated. Hybrid immunity against XBB was lower than against BA.4 or BA.5, especially in adolescents. Early vaccination of previously uninfected children before their first SARS-CoV-2 exposure could potentially strengthen population immunity resilience against future variants. FUNDING: None.

Impact of COVID-19 pandemic early response measures on myocardial infarctions and acute cardiac care in Singapore.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics.

COVID-19 infection after SARS-CoV-2 mRNA vaccination in Multiple Sclerosis, AQP4-antibody NMOSD and MOGAD patients during the Omicron subvariant BA.1/2 wave in Singapore.

BACKGROUND: The SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore. METHODS: This was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination. RESULTS: Two hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy. CONCLUSIONS: The Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.

Using the increasing vaccination model and the moderating roles of chronic medical conditions and education to understand COVID-19 vaccination uptake in Singapore.

COVID-19 vaccination programmes have helped reduce deaths and morbidity from the pandemic and allowed for the resumption of normal life. However, vaccine hesitancy remains an issue even with recurrent surges in COVID-19 cases due to new SARS-CoV-2 variants. Purpose: To elucidate psychosocial factors that contribute to our understanding of vaccine hesitancy. 676 Participants in Singapore took part in an online survey on vaccine hesitancy and uptake between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. The responses were analyzed using structural equation modeling (SEM). The study found that confidence in the COVID-19 vaccines and risk perception of the COVID-19 situation are significantly associated with vaccination intention, while vaccination intention is also significantly associated with reported vaccination status. Additionally, certain chronic medical conditions moderate the relationship between vaccine confidence/risk perception and vaccine intention. This study contributes to our understanding of factors behind vaccination uptake which can help anticipate challenges to future vaccination campaigns for the next pandemic.

COVID-19 vaccination programmes have helped reduce deaths from the pandemic and allowed for the resumption of normal life. However, vaccine hesitancy among the public remains an issue even with recurrent surges in COVID-19 cases due to new SARS-CoV-2 variants. To understand psychosocial factors that contribute to vaccine uptake, this study surveyed 676 participants in Singapore through an online survey on vaccine hesitancy and uptake between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness factors were collected. The responses were analyzed using structural equation modeling (SEM). The study found that confidence in the COVID-19 vaccines and risk perception of the COVID-19 situation are significantly associated with vaccination intention, while vaccination intention is also significantly associated with reported vaccination status. Additionally, certain chronic medical conditions moderate the relationship between vaccine confidence/risk perception and vaccine intention. This study contributes to our understanding of factors behind vaccination uptake which can help anticipate challenges to future vaccination campaigns for the next pandemic.

Preliminary case report on the SARS-CoV-2 cluster in the UK, France, and Spain

Almost half of the confirmed COVID-19 cases detected so far in the United Kingdom are part of a large cluster of 13 British nationals who tested positive for SARS-CoV-2 in the UK, Spain, and France. Transmissions among this cluster occurred at a ski resort in France, and originated from a single infected traveller returning from a conference in Singapore where he acquired the virus. At least 21 individuals were exposed to the virus, tested, and quarantined, with 13 of those testing positive between the period of 6th February and 15th February. Here, all publicly available information about the primarily UK/France cluster is consolidated, providing a complete and accessible summary of the cases and their connections. Notable in this cluster are the number of individuals infected, the apparent absence of any severe illness among those infected, and a case of a "delayed positive" test during isolation after initially testing negative, at least 7 days after last possible contact.

Serial Intervals and Incubation Periods of SARS-CoV-2 Omicron and Delta Variants, Singapore.

We compared serial intervals and incubation periods for SARS-CoV-2 Omicron BA.1 and BA.2 subvariants and Delta variants in Singapore. Median incubation period was 3 days for BA.1 versus 4 days for Delta. Serial interval was 2 days for BA.1 and 3 days for BA.2 but 4 days for Delta.

Technology-enabled virtual ward for COVID management of the elderly and immunocompromised in Singapore: a descriptive cohort.

BACKGROUND: To address the hospital bed demand for Delta and Omicron surges in Singapore, the National University Health System (NUHS) developed a COVID Virtual Ward to relieve bed pressures on its three acute hospitals-National University Hospital, Ng Teng Fong General Hospital, Alexandra Hospital. To serve a multilingual population, the COVID Virtual Ward featuring protocolized teleconsultation of high-risk patients, use of a vital signs chatbot, supplemented by home visits where necessary. This study aims to evaluate the safety, outcomes and utilisation of the Virtual Ward as a scalable response to COVID-19 surges. METHODS: This is a retrospective cohort study of all patients admitted to the COVID Virtual Ward between 23 September to 9 November 2021. Patients were defined as "early discharge" if they were referred from inpatient COVID-19 wards and "admission avoidance" if they were referred directly from primary care or emergency services. Patient demographics, utilisation measures and clinical outcomes were extracted from the electronic health record system. The primary outcomes were escalation to hospital and mortality. Use of the vital signs chatbot was evaluated by examining compliance levels, need for automated reminders and alerts triggered. Patient experience was evaluated using data extracted from a quality improvement feedback form. RESULTS: 238 patients were admitted to the COVID Virtual Ward from 23 September to 9 November, of whom 42% were male, 67.6% of Chinese ethnicity. 43.7% were over the age of 70, 20.5% were immunocompromised, and 36.6% were not fully vaccinated. 17.2% of patients were escalated to hospital and 2.1% of patients died. Patients who were escalated to hospital were more likely to be immunocompromised or to have a higher ISARIC 4C-Mortality Score. There were no missed deteriorations. All patients received teleconsults (median of 5 teleconsults per patient, IQR 3-7). 21.4% of patients received home visits. 77.7% of patients engaged with the vital signs chatbot, with a compliance rate of 84%. All patients would recommend the programme to others in their situation. CONCLUSIONS: Virtual Wards are a scalable, safe and patient-centered strategy to care for high risk COVID-19 patients at home. TRIAL REGISTRATION: NA.

Co-incidence of BA.1 and BA.2 at the start of Singapore's Omicron wave revealed by Community and University Campus wastewater surveillance.

Wastewater surveillance (WWS) has been globally recognised to be a useful tool in quantifying SARS-CoV-2 RNA at the community and residential levels without biases associated with case-reporting. The emergence of variants of concern (VOCs) have given rise to an unprecedented number of infections even though populations are increasingly vaccinated. This is because VOCs have been reported to possess higher transmissibility and can evade host immune responses. The B.1.1.529 lineage (Omicron) has severely disrupted global plans to return to normalcy. In this study, we developed an allele-specific (AS) RT-qPCR assay which simultaneously targets the stretch of deletions and mutations in the spike protein from position 24-27 for quantitative detection of Omicron BA.2. Together with previous assays that detect mutations associated with Omicron BA.1 (deletion at position 69 and 70) and all Omicron (mutation at position 493 and 498), we report the validation and time series of these assays from September 2021 to May 2022 using influent samples from two wastewater treatment plants and across four University campus sites in Singapore. Viral RNA concentrations at the treatment plants corroborate with locally reported clinical cases, AS RT-qPCR assays revealed co-incidence of Omicron BA.1 and BA.2 on 12 January 2022, almost two months after initial BA.1 detection in South Africa and Botswana. BA.2 became the dominant variant by the end of January 2022 and completely displaced BA.1 by mid-March 2022. University campus sites were similarly positive for BA.1 and/or BA.2 in the same week as first detection at the treatment plants, where BA.2 became rapidly established as the dominant lineage within three weeks. These results corroborate clinical incidence of the Omicron lineages in Singapore and indicate minimal silent circulation prior to January 2022. The subsequent simultaneous spread of both variant lineages followed strategic relaxation of safe management measures upon meeting nationwide vaccination goals.

Protective immunity of SARS-CoV-2 infection and vaccines against medically attended symptomatic omicron BA.4, BA.5, and XBB reinfections in Singapore: a national cohort study.

BACKGROUND: Despite a large proportion of the population having been vaccinated and infected, Singapore had SARS-CoV-2 waves driven by the BA.5 and XBB sublineages of the omicron (B.1.1.529) variant. Data on the protective immunity against medically attended, symptomatic reinfections with omicron BA.4, BA.5, and XBB conferred by previous SARS-CoV-2 infections and vaccinations are scarce. We therefore aimed to derive information from Singapore's experience as one of the first countries with an XBB-driven wave. METHODS: For this retrospective national cohort study, we used information from official databases of the Ministry of Health of Singapore to assess hybrid immunity (obtained from previous infection and vaccination) against medically attended, symptomatic BA.4 and BA.5 reinfections from Oct 1, 2022, to Nov 1, 2022, and medically attended, symptomatic XBB reinfections from Oct 18, 2022, to Nov 1, 2022, among Singapore citizens and permanent residents aged at least 18 years. All individuals with acute respiratory symptoms who presented at any health-care facility in Singapore between the stated dates were tested for SARS-CoV-2. Individuals were grouped into SARS-CoV-2-naive, pre-omicron, omicron BA.1, and omicron BA.2 groups according to their previous infection status. Data were also stratified by time from first infection to analyse the waning of immunity. Incidence rate ratios (IRRs) were measured by generalised linear Poisson regressions, with SARS-CoV-2-naive individuals as the reference group, and protective immunity was calculated as one minus the risk ratio multiplied by 100. FINDINGS: 2 456 791 individuals were included in the study, contributing 53·1 million person-days of observation for the SARS-CoV-2-naive group, 3·4 million person-days for the pre-omicron group, 6·6 million person-days for the BA.1 group, and 13·7 million person-days for the BA.2 group between Oct 1, 2022, and Nov 1, 2022. Compared with SARS-CoV-2-naive individuals, first infections with pre-omicron variants did not confer protection against reinfection with BA.4 or BA.5 (IRR 0·87 [95% CI 0·73-1·05] for pre-omicron infection with booster vaccination) or XBB (IRR 1·29 [1·23-1·35] for pre-omicron infection with booster vaccination). Previous BA.2 infection with booster provided the greatest protection against reinfection, but this was lower against reinfection with XBB (protective immunity 51%; 95% CI 49-53) than against reinfection with BA.4 or BA.5 (78%; 74-82). Protection conferred by previous BA.2 infection against XBB reinfection waned faster over time from first infection (from 74% [72-75] at 3-6 months to 49% [47-52] at 7-8 months) than protection against BA.4 or BA.5 reinfection (from 87% [82-90] at 3-6 months to 74% [66-80] at 7-8 months). INTERPRETATION: Protection against XBB reinfection conferred by a previous omicron infection with vaccination was lower and waned faster than protection against BA.4 or BA.5 reinfection, which is indicative of the greater immune evasiveness of the XBB sublineage. Although severe COVID-19 is uncommon, populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and infection, as reflected by substantially higher reinfection rates during Singapore's XBB wave than during the previous BA.5-driven wave. Policy makers could consider emerging public health interventions, such as omicron-adapted bivalent vaccines, to maintain population immunity against COVID-19. FUNDING: None.

Rodent activity in municipal waste collection premises in Singapore: an analysis of risk factors using mixed-effects modelling.

Refuse storage and collection systems are potential sources of food and harbourage areas for rodents which transmit pathogens. We examined the factors associated with rodent activity in public housing municipal waste collection premises in a highly urbanized city-state. We analysed data from April 2019 to March 2020 in mixed-effects logistic regression models to examine the independent factors associated with rodent activity in central refuse chute rooms (CRCs), individual refuse chute (IRC) bin chambers and bin centres. We accounted for within-year patterns, repeated measures and nested effects. We observed a heterogeneous spatial distribution of rodent activity. Rodent droppings were strongly associated with rodent activity in CRCs (aOR: 6.20, 95% CI: 4.20-9.15), bin centres (aOR: 3.61, 95% CI: 1.70-7.64) and IRC bin chambers (aOR: 90.84, 95% CI: 70.13-117.67). Gnaw marks were positively associated with rodent activity in CRCs (aOR: 5.61, 95% CI: 3.55-8.97) and IRC bin chambers (aOR: 2.05, 95% CI: 1.43-2.95), as were rub marks in CRCs (aOR: 5.04, 95% CI: 3.44-7.37) and IRC bin chambers (aOR: 3.07, 95% CI: 1.74-5.42). Each burrow increased the odds of rodent sightings in bin centres (aOR: 1.03, 95% CI: 1.00-1.06). The odds of rodent sightings in an IRC bin chamber increased with every additional bin chute chamber within the same block (aOR: 1.04, 95% CI: 1.01-1.07). We identified several factors that well predicted rodent activity in waste collection premises. Municipal estate managers with limited resources can adopt a risk-based approach in tailoring the focus of their rodent control interventions.

Economic Analysis of Border Control Policies during COVID-19 Pandemic: A Modelling Study to Inform Cross-Border Travel Policy between Singapore and Thailand.

With countries progressing towards high COVID-19 vaccination rates, strategies for border reopening are required. This study focuses on Thailand and Singapore, two countries that share significant tourism visitation, to illustrate a framework for optimizing COVID-19 testing and quarantine policies for bilateral travel with a focus on economic recovery. The timeframe is the month of October 2021, when Thailand and Singapore were preparing to reopen borders for bilateral travel. This study was conducted to provide evidence for the border reopening policy decisions. Incremental net benefit (INB) compared to the pre-opening period was quantified through a willingness-to-travel model, a micro-simulation COVID-19 transmission model and an economic model accounting for medical and non-medical costs/benefits. Multiple testing and quarantine policies were examined, and Pareto optimal (PO) policies and the most influential components were identified. The highest possible INB for Thailand is US $125.94 million, under a PO policy with no quarantine but with antigen rapid tests (ARTs) pre-departure and upon arrival to enter both countries. The highest possible INB for Singapore is US $29.78 million, under another PO policy with no quarantine on both sides, no testing to enter Thailand, and ARTs pre-departure and upon arrival to enter Singapore. Tourism receipts and costs/profits of testing and quarantine have greater economic impacts than that from COVID-19 transmission. Provided healthcare systems have sufficient capacity, great economic benefits can be gained for both countries by relaxing border control measures.

The shift of percent excess mortality from zero-COVID policy to living-with-COVID policy in Singapore, South Korea, Australia, New Zealand and Hong Kong SAR.

Introduction: With the economic recession and pandemic fatigue, milder viral variants and higher vaccine coverage along the time lay the basis for lifting anti-COVID policies to restore COVID-19 normalcy. However, when and how to adjust the anti-COVID policies remain under debate in many countries. Methods: In this study, four countries (Singapore, South Korea, Australia, and New Zealand) and one region (Hong Kong SAR), that have shifted from the zero-COVID (ZC) policy to or close to the living-with-COVID (LWC) during or after the Omicron outbreak, were selected as research objects. All-cause mortality data were collected for these objects from 2009 to 2019. The expected mortality was estimated by a simple linear regression method. Excess mortality over time was calculated as the difference between the expected mortality and the observed mortality. Finally, percent excess mortality (PEM) was calculated as the excess mortality divided by the expected mortality. Results: In the examined four countries, PEM fluctuated around 0% and was lower than 10% most of the time under the ZC policy before 2022. After shifting to the LWC policy, all the examined countries increased the PEM. Briefly, countries with high population density (Singapore and South Korea) experienced an average PEM of 20-40% during the first half of 2022, and followed by a lower average PEM of 15-18% during the second half of 2022. For countries with low population density under the LWC policy, Australia experienced an average PEM of 39.85% during the first half of 2022, while New Zealand was the only country in our analysis that achieved no more than 10% in average PEM all the time. On the contrary, Hong Kong SAR under their ZC policy attained an average PEM of 71.14% during the first half of 2022, while its average PEM decreased to 9.19% in the second half of 2022 with LWC-like policy. Conclusion: PEM under different policies within each country/region overtime demonstrated that the mortality burden caused by COVID-19 had been reduced overtime. Moreover, anti-COVID policies are suggested to control the excess mortality to achieve as low as 10% in PEM.

Cost benefit analysis of alternative testing and quarantine policies for travelers for infection control: A case study of Singapore during the COVID-19 pandemic.

Background: Border control mitigates local infections but bears a heavy economic cost, especially for tourism-reliant countries. While studies have supported the efficacy of border control in suppressing cross-border transmission, the trade-off between costs from imported and secondary cases and from lost economic activities has not been studied. This case study of Singapore during the COVID-19 pandemic aims to understand the impacts of varying quarantine length and testing strategies on the economy and health system. Additionally, we explored the impact of permitting unvaccinated travelers to address emerging equity concerns. We assumed that community transmission is stable and vaccination rates are high enough that inbound travelers are not dissuaded from traveling. Methods: The number of travelers was predicted considering that longer quarantine reduces willingness to travel. A micro-simulation model predicted the number of COVID-19 cases among travelers, the resultant secondary cases, and the probability of being symptomatic in each group. The incremental net monetary benefit (INB) of Singapore was quantified under each border-opening policy compared to pre-opening status, based on tourism receipts, cost/profit from testing and quarantine, and cost and health loss due to COVID-19 cases. Results: Compared to polymerase chain reaction (PCR), rapid antigen test (ART) detects fewer imported cases but results in fewer secondary cases. Longer quarantine results in fewer cases but lower INB due to reduced tourism receipts. Assuming the proportion of unvaccinated travelers is small (8% locally and 24% globally), allowing unvaccinated travelers will accrue higher INB without exceeding the intensive care unit (ICU) capacity. The highest monthly INB from all travelers is $2,236.24 m, with 46.69 ICU cases per month, achieved with ARTs at pre-departure and on arrival without quarantine. The optimal policy in terms of highest INB is robust under changes to various model assumptions. Among all cost-benefit components, the top driver for INB is tourism receipts. Conclusions: With high vaccination rates locally and globally alongside stable community transmission, opening borders to travelers regardless of vaccination status will increase economic growth in the destination country. The caseloads remain manageable without exceeding ICU capacity, and costs of cases are offset by the economic value generated from travelers.

Results from a systematic programme of evaluating COVID-19 reinfection cases in the early phase of the pandemic, Singapore.

OBJECTIVES: The objectives of this study were to describe the coronavirus disease caused by SARS-CoV-2 (COVID-19) reinfection evaluation algorithm used in the early phase of the pandemic in Singapore and analyze the clinical and laboratory characteristics of the cases evaluated. METHODS: We performed a retrospective case-control analysis including all COVID-19 cases evaluated for possible reinfection under the local COVID-19 reinfection evaluation programme between 1 June 2020-30 June 2021. Whole genome sequencing (WGS) was used as confirmatory testing. We compared all reinfection ("RI") cases against those who were evaluated but eventually assessed not to be reinfection ("non-RI"). RESULTS: There were 74 possible reinfection cases evaluated through the programme, of which 32 were subsequently classified as RI. There was strong statistical evidence that RI cases had a longer interval between 1st and 2nd episode (mean 297 days; 95%-confidence interval (CI) 267-327) compared to non-RI cases (mean 186 days; 95%-CI 144-228). The cycle threshold (Ct) value of initial polymerase chain rection (PCR) at 2nd episode was also found to be significantly lower in RI cases (mean 23; 95%-CI 20-26) compared to non-RI cases (mean 34; 95%-CI 32-36). There was no significant difference in the proportion of individuals who had fever, acute respiratory symptoms or asymptomatic in both groups. Delta and beta variants were most commonly identified from WGS and provide indication of re-infection as these were not 'wild-type' and were not circulating during the time period of the index infection. CONCLUSIONS: Using a combination of serologic, microbiologic and genomic criteria to evaluate possible reinfection cases is useful and can provide a framework for evaluation that may be modified for future similar situations.