Publications by authors named "David Lye"

Background: In the absence of effective pharmaceutical interventions early in an infectious disease outbreak, non-pharmaceutical measures, especially isolating infected individuals, critically limit its impact. The ongoing COVID-19 pandemic has sparked debates on optimal isolation guidelines. This study proposes a variable isolation period approach (variable-period approach), tailoring isolation durations for distinct population groups with varied viral load dynamics.

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Background: Significant heterogeneity has been reported in estimates of long-term sequelae following SARS-CoV-2 infection in pregnant women, and most studies were conducted pre-Omicron and pre-dated vaccination rollout. Less severe COVID-19 attributed to milder Omicron may potentially attenuate risk of post-COVID-19 sequelae.

Objective: We sought to examine long-term risk of new-incident multi-systemic sequelae following SARS-CoV-2 Delta/Omicron infection in a population-based cohort of pregnant women, contrasted against a)test-negatives; b)infected non-pregnant women of childbearing age.

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Dengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore adults.

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Mathematical models of viral dynamics are crucial in understanding infection trajectories. However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load data often includes limited sparse observations with significant heterogeneity. This study aims to: (1) understand the impact of patient characteristics in shaping the temporal viral load trajectory and (2) establish a data collection protocol (DCP) to reliably reconstruct individual viral load trajectories.

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The COVID-19 pandemic highlighted the critical need for well-established clinical research networks capable of rapid response during infectious disease outbreaks. In Southeast Asia, the absence of active research networks at the onset of the COVID-19 contributed to gaps in regional preparedness. This manuscript discusses the challenges and opportunities identified during a regional workshop held in Singapore (February 26 to March 1, 2024), which brought together 130 stakeholders from across the region.

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Objectives: Most studies on long-term sequelae of SARS-CoV-2 infection in children were conducted pre-Omicron and pre-dated vaccination rollout. We examined long-term risk of new-incident multi-systemic sequelae following SARS-CoV-2 Delta/Omicron infection in a multi-ethnic Asian paediatric population.

Methods: Retrospective cohort study of Singaporean children aged 1-17 years infected during Delta/Omicron BA.

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Background: Vaccination has been shown to attenuate the risk of post-acute sequelae following SARS-CoV-2 infection. However, no prior population-based studies have evaluated if updated bivalent boosters reduce risk of post-acute sequelae following Omicron-variant infection, versus ancestral vaccines.

Methods: National databases were utilised to construct a population-based cohort of adult individuals infected during Omicron-predominant transmission.

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The ISARIC 4C Mortality score was developed to predict mortality risk among patients with COVID-19. Its performance among vaccinated individuals is understudied. This is a retrospective study of all patients with SARS-CoV-2 infection admitted to the National Centre for Infectious Diseases, Singapore, from January-2020 to December-2021.

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Article Synopsis
  • The study assesses the population-wide risk-benefit ratio of COVID-19 vaccination during the Omicron variant phase, focusing on mortality and cardiovascular events post-vaccination and infection.
  • Conducted in Singapore from January to December 2022 with over 3 million participants, researchers utilized Cox regression to evaluate risks for various timeframes post-vaccination/infection.
  • Results showed no increased risk of mortality or cardiovascular events after vaccination, but older adults had elevated mortality risks after infection, particularly with vaccine-breakthrough infections, while cardiovascular risks were higher 1-2 months post-infection across all age groups.
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Background: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine.

Methods: We conducted a randomized, participant-blinded, controlled trial.

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Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks.

Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records.

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Objectives: Significant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans.

Methods: National COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022-4 August 2023).

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Importance: Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.

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Background: Shared decision-making (SDM) on antibiotic therapy may improve antibiotic use in tertiary hospitals, but hospitalised patients are apprehensive about being involved in it. Understanding the facilitators and barriers to SDM can inform the design and implementation of interventions to empower these patients to engage in SDM on their antibiotic therapies.

Methods: We conducted qualitative interviews with 23 adult patients purposively sampled with maximum variation from the three largest tertiary-care hospitals in Singapore (April 2019─October 2020).

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Article Synopsis
  • - A study evaluated the immune responses from two types of booster vaccinations (homologous BNT162b2 and heterologous mRNA-1273) in individuals who had previously received BNT162b2 and had not been infected with SARS-CoV-2.
  • - The results showed that those who received the heterologous booster had significantly higher antibody levels against wild-type SARS-CoV-2 six months after vaccination, and many participants experienced Omicron breakthrough infections regardless of the booster type.
  • - The findings suggest that while booster shots are beneficial, the immune response decreases significantly over time, highlighting the need for timely booster administration before infection surges. !*
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Article Synopsis
  • A study was conducted in Singapore to explore whether having a prior dengue infection affects the risk and severity of getting COVID-19, particularly in a population where both diseases can overlap.
  • Researchers analyzed data from over 3 million individuals, looking at the relationship between prior dengue infections and subsequent SARS-CoV-2 cases during a time of increased COVID-19 transmission from Delta and Omicron variants.
  • The findings revealed that prior dengue infections slightly increase the risk of contracting SARS-CoV-2 and significantly heighten the likelihood of hospitalization and severe outcomes from COVID-19.
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Article Synopsis
  • Multiple Omicron sub-lineages, particularly XBB and XBB.1.5, have become the global dominant variants, showcasing their ability to evade immunity despite minor genetic changes from previous variants.
  • Researchers conducted a pseudovirus neutralization test with convalescent sera from individuals who recovered from SARS-CoV infections, including various Omicron subvariants.
  • The findings showed no significant cross-neutralization among the different strains, suggesting that current SARS-related coronaviruses should be classified into three distinct serotypes.
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Objectives: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants.

Methods: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.

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Background: Data on protection afforded by updated coronavirus disease 2019 (COVID-19) vaccines (bivalent/XBB 1.5 monovalent) against the emergent JN.1 variant remain limited.

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Objectives: Evidence suggests that some COVID-19 survivors experience a wide range of post-COVID-19 sequelae; however, the majority of studies were conducted before the emergence of the milder Omicron variant. We examined the post-acute risk of new-incident cardiovascular complications after SARS-CoV-2 infection in a multi-ethnic Asian population, during Omicron predominance.

Methods: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals with confirmed SARS-CoV-2 infection during Omicron BA.

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Background: Individuals with chronic lung disease (CLD) are more susceptible to respiratory viral infections; however, significant heterogeneity exists in the literature on CLD and COVID-19 outcomes. Data are lacking on outcomes with newer variants (eg, Omicron) and in vaccinated and boosted populations.

Research Question: What are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission in a highly vaccinated and boosted population-based cohort?

Study Design And Methods: Outcomes of Delta and Omicron SARS-CoV-2 infection in a highly vaccinated and boosted cohort of adult Singaporeans with CLD (including asthma, COPD, bronchiectasis, and pulmonary fibrosis) were contrasted against matched population control participants.

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Background: While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was contrasted against that following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a multi-ethnic adult Asian population.

Methods: National testing and healthcare claims that databases in Singapore were utilized to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 July 2021 to 31 October 2022).

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There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008.

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Objectives: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection.

Design: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs).

Results: Ninety-eight patients completed primary vaccination prepregnancy (29.

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