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.

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.

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.

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.

Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Dengue is a severe environmental public health challenge in tropical and subtropical regions. In Singapore, decreasing seroprevalence and herd immunity due to successful vector control has paradoxically led to increased transmission potential of the dengue virus. We have previously demonstrated that incompatible insect technique coupled with sterile insect technique (IIT-SIT), which involves the release of X-ray-irradiated male Wolbachia-infected mosquitoes, reduced the Aedes aegypti population by 98% and dengue incidence by 88%. This novel vector control tool is expected to be able to complement current vector control to mitigate the increasing threat of dengue on a larger scale. We propose a multi-site protocol to study the efficacy of IIT-SIT at reducing dengue incidence. METHODS/DESIGN: The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints: (1) odds ratio of Wolbachia exposure distribution (i.e., probability of living in an intervention cluster) among laboratory-confirmed reported dengue cases compared to test-negative controls and (2) laboratory-confirmed reported dengue counts normalized by population size in intervention versus non-intervention clusters. DISCUSSION: This study will provide evidence from a multi-site, randomized controlled trial for the efficacy of IIT-SIT in reducing dengue incidence. The trial will provide valuable information to estimate intervention efficacy for this novel vector control approach and guide plans for integration into national vector control programs in dengue-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682 . Registered on 16 August 2022. Retrospectively registered.

Estimating the excess bed days and economic burden of healthcare-associated infections in Singapore public acute-care hospitals.

We estimated the annual bed days lost and economic burden of healthcare-associated infections to Singapore hospitals using Monte Carlo simulation. The mean (standard deviation) cost of a single healthcare-associated infection was S$1,809 (S$440) [or US$1,362 (US$331)]. This translated to annual lost bed days and economic burden of 55,978 (20,506) days and S$152.0 million (S$37.1 million) [or US$114.4 million (US$27.9 million)], respectively.

Bayesian SIR model with change points with application to the Omicron wave in Singapore.

The Omicron variant has led to a new wave of the COVID-19 pandemic worldwide, with unprecedented numbers of daily confirmed new cases in many countries and areas. To analyze the impact of society or policy changes on the development of the Omicron wave, the stochastic susceptible-infected-removed (SIR) model with change points is proposed to accommodate the situations where the transmission rate and the removal rate may vary significantly at change points. Bayesian inference based on a Markov chain Monte Carlo algorithm is developed to estimate both the locations of change points as well as the transmission rate and removal rate within each stage. Experiments on simulated data reveal the effectiveness of the proposed method, and several stages are detected in analyzing the Omicron wave data in Singapore.

The predictors of health-enhancing physical activity among working women in Singapore two years into COVID-19: a cross-sectional study.

Physical activity (PA) levels may have changed since the COVID-19 pandemic. However, these changes are not well understood. The study aimed to describe the PA level and examine the predictive factors of a health-enhancing PA level among working women in Singapore two years into the COVID-19 pandemic. We undertook a cross-sectional descriptive correlational study. Three hundred participants were recruited and completed the online questionnaire between October and November 2021. In the PA analysis of 217 participants, only 32.7% of the participants achieved a health-enhancing PA level, while 44.7% of the total sample sat for 7 h or more daily. In the univariate analysis, occupation, nationality, monthly income, and average daily sitting hours were significantly associated with a high PA level. The current mode of work, living arrangement, and health-promoting lifestyle profile II_physical activity score remained significant in both univariate and multivariate analyses. Participants who worked from home and stayed with their families were less likely to achieve a health-enhancing PA level than those who had a regular workplace and did not stay with their families. Working women with a health-promoting physically active lifestyle were likelier to achieve a health-enhancing PA level. The long daily sitting time and suboptimal health-enhancing PA participation underscore the need for health promotion initiatives for working women.

COVID-19 vaccine acceptance and hesitancy among primary healthcare workers in Singapore.

BACKGROUND: Factors affecting COVID-19 vaccine acceptance and hesitancy among primary healthcare workers (HCW) remain poorly understood. This study aims to identify factors associated with vaccine acceptance and hesitancy among HCW. METHODS: A multi-centre online cross-sectional survey was performed across 6 primary care clinics from May to June 2021, after completion of staff vaccination exercise. Demographics, profession, years working in healthcare, residential status, presence of chronic medical conditions, self-perceived risk of acquiring COVID-19 and previous influenza vaccination were collected. HCW who accepted vaccine were then asked to rank their top 5 reasons for vaccine acceptance; HCW who were vaccine hesitant had to complete the 15-item 5C scale on psychological antecedents of vaccination. RESULTS: Five hundred fifty seven out of 1182 eligible HCW responded (47.1%). Twenty nine were excluded due to contraindications. Among 528 respondents, vaccine acceptance rate was 94.9% (n = 501). There were no statistically significant differences in COVID-19 vaccine acceptance between sex, age, ethnicity, profession, number of years in healthcare, living alone, presence of chronic diseases, self-perceived risk or previous influenza vaccination. The top 3 reasons for COVID-19 vaccine acceptance ranked by 501 HCW were to protect their family and friends, protect themselves from COVID-19 and due to high risk of acquiring COVID-19 because of their jobs. HCW with suspected or confirmed COVID-19 exposure were 3.4 times more likely to rank 'high risk at work' as one of the top reasons for vaccine acceptance (χ2 = 41.9, p < 0.001, OR = 3.38, 95%C.I. 2.32-4.93). High mean scores of 'Calculation' (5.79) and low scores for 'Constraint' (2.85) for 5C components among vaccine hesitant HCW (n = 27) highlighted that accessibility was not a concern; HCW took time to weigh vaccine benefits and consequences. CONCLUSION: COVID-19 vaccine hesitancy is a minute issue among Singapore primary HCW, having achieved close to 95% acceptance rate. COVID-19 exposure risk influences vaccine acceptance; time is required for HCW to weigh benefits against the risks. Future studies can focus on settings with higher hesitancy rates, and acceptance of booster vaccinations with the emergence of delta and omicron variants.

COVID-19 vaccination-related attendance at a pediatric emergency department in Singapore among 12- to 18-year old adolescents.

BACKGROUND: Singapore was one of the first countries to begin COVID-19 vaccination with the BNT162b2 vaccine for adolescents aged 12-18 years. This study evaluates the incidence of COVID-19 vaccine related attendances to a Pediatric Emergency Department (PED) to understand post-vaccination health behaviors among adolescents. METHODS: This was a retrospective review of electronic medical records over a 4 month period, from the start of the adolescent vaccination drive to when more than 85% of this group had been fully vaccinated. RESULTS: The incidence of COVID-19 vaccination-related presentations to our PED was 3.1% over 4 months (291 of 9387 PED attendances), with a peak daily incidence of 15.4% (14 of 91 attendances). Presentations were characterized by severity into: severe (3.4%), moderate (7.9%) or mild (88.7%) based on predefined criteria. The most common presenting complaints were chest pain (58.8%), dyspnea (28.2%) and palpitations (22.6%). Hospitalization was required in only 6.2% of attendances. Patients with moderate-severe presentations were 0.7 years older (p = 0.030), more likely to have underlying drug allergies (p = 0.048) and had higher rates of hospitalization (p < 0.005) compared to mild presentations. Despite concerns of cardiac inflammation, chest pain related attendances were less likely to be severe (p < 0.005) with reduced hospitalization need (p = 0.043) compared to other presentations. Investigations beyond clinical assessment comprised 91% of attendances, but abnormalities were only found in 6.4% cases. CONCLUSION: Our study supports current evidence that COVID-19 vaccination is safe amongst adolescents. We highlight the health behaviors among adolescents post-vaccination, which is partly driven by media reports on vaccine side effects and an element of anxiety. While most of the presentations were mild, these can have implications on health resource utilization, particularly in an ongoing pandemic. As healthcare workers, we have an ongoing role to ensure accurate information on vaccine safety is communicated effectively to the public.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

The requirements of nucleic acid test for COVID-19 during public health emergency: Current regulatory in Taiwan, Singapore, and the United States.

In mid-2022, the COVID-19 cases have reached close to 562 million, but its overall infection rate is hard to confirm. Even with effective vaccines, break-through infections with new variants occur, and safe and reliable testing still plays a critical role in isolation of infected individuals and in control of an outbreak of a COVID-19 pandemic. In response to this urgent need, the diagnostic tests for COVID-19 are rapidly evolving and improving these days. The health authorities of many countries issued requirements for detecting SARS-CoV-2 diagnosis tests during the pandemic and have timely access to these tests to ensure safety and effectiveness. In this study, we compared the requirements of EUA in Taiwan, Singapore, and the United States. For the performance evaluations of nucleic acid extraction, inclusivity, limit of detection (LoD), cross-reactivity, interference, cutoff, and stability, the requirements are similar in the three countries. The use of natural clinical specimens is needed for clinical evaluation in Taiwan and the United States. However, carry-over and cross-contamination studies can be exempted in Taiwan and the United States but are required in Singapore. This review outlines requirements and insight to guide the test developers on the development of IVDs. Considering the rapidly evolving viruses and severe pandemic of COVID-19, timely and accurate diagnostic testing is imperative to the management of diseases. As noted above, the performance requirements for SARS-CoV-2 nucleic acid tests are similar between Taiwan, Singapore and the United States. The differences are mainly in two points: the recommended microorganisms for cross-reactivity study, and the specimen requirement for clinical evaluation. This study provides an overview of current requirements of SARS-CoV-2 nucleic acid tests in Taiwan, Singapore, and the United States.

Role of Occupational Health Services in Planning and Implementing of Staff COVID-19 Vaccination Clinic: A Tertiary Hospital Experience in Singapore.

CONTEXT: Healthcare workers all over the world were prioritized for vaccination against COVID-19 in view of the high-risk nature of their job scopes when vaccines were first available in late 2020. Vaccine hesitancy was an important problem to tackle in order to achieve a high vaccination rate, especially for vaccines that were developed using mRNA technology. We aimed to use the '3Cs' model to address vaccine hesitancy to ensure maximal uptake of the Pfizer-BioNTech vaccine among healthcare workers in a tertiary hospital in Singapore. METHODS: Various measures were used to reduce the confidence, complacency, and convenience barriers. The staff vaccination clinic was on-site and centralized, with appointments given in advance to ensure vaccine availability and to reduce wait time, providing convenience to staff. Direct and repeated communications with the staff via multiple channels were used to address vaccine safety and efficacy so as to promote confidence in the vaccines and overcome complacency barriers. To further encourage staff to get vaccinated, staff were allowed time off for vaccination when at work. Staff with a high risk of exposure to COVID-19 or those caring for immunocompromised patients were prioritized to take the vaccines first. The collection of data on adverse events was via on-site monitoring and consultation at Occupational Health Clinic (OHC). RESULTS: Nearly 80% of staff had completed vaccination when the vaccination exercise ended at the end of March 2021. With the loosening of the contraindications to vaccination over time, staff vaccination rates reached 89.3% in early July and nearly 99.9% by the end of the year. No major or serious vaccine-related medication or administration errors were reported. No staff had anaphylaxis. CONCLUSIONS: By using the '3Cs' model to plan out the vaccination exercise, it is possible to achieve a high vaccination rate coupled with effective and customized communications. This multi-disciplinary team approach can be adapted to guide vaccination efforts in various settings in future pandemics.

Psychological and behavioral responses to the declaration of COVID-19 as a pandemic: A comparative study of Hong Kong, Singapore, and the U.S.

What is the effect of declaring a pandemic? This research assesses behavioral and psychological responses to the WHO declaration of the COVID-19 pandemic, in Hong Kong, Singapore, and the U.S. We surveyed 3,032 members of the general public in these three regions about the preventative actions they were taking and their worries related to COVID-19. The WHO announcement on March 11th, 2020 created a quasi-experimental test of responses immediately before versus after the announcement. The declaration of the pandemic increased worries about the capacity of the local healthcare system in each region, as well as the proportion of people engaging in preventative actions, including actions not recommended by medical professionals. The number of actions taken correlates positively with anxiety and worries. Declaring the COVID-19 crisis as a pandemic had tangible effects-positive (increased community engagement) and negative (increased generalized anxiety)-which manifested differently across regions in line with expectancy disconfirmation theory.