Prescribing Antibiotics in Public Primary Care Clinics in Singapore: A Retrospective Cohort Study.

BACKGROUND: Antibiotic prescription practices in primary care in Singapore have received little scholarly attention. In this study, we ascertained prescription prevalence and identified care gaps and predisposing factors. METHODS: A retrospective study was conducted on adults (>21 years old) at six public primary care clinics in Singapore. Prescriptions >14 days were excluded. Descriptive statistics were used to showcase the prevalence data. We used chi-square and logistic regression analyses to identify the factors affecting care gaps. RESULTS: A total of 141,944 (4.33%) oral and 108,357 (3.31%) topical antibiotics were prescribed for 3,278,562 visits from 2018 to 2021. There was a significant reduction in prescriptions (p < 0.01) before and after the pandemic, which was attributed to the 84% reduction in prescriptions for respiratory conditions. In 2020 to 2021, oral antibiotics were most prescribed for skin (37.7%), genitourinary (20.2%), and respiratory conditions (10.8%). Antibiotic use in the "Access" group (WHO AWaRe classification) improved from 85.6% (2018) to 92.1% (2021). Areas of improvement included a lack of documentation of reasons for antibiotic use, as well as inappropriate antibiotic prescription for skin conditions. CONCLUSION: There was a marked reduction in antibiotic prescriptions associated with the onset of the COVID-19 pandemic. Further studies could address the gaps identified here and evaluate private-sector primary care to inform antibiotic guidelines and the local development of stewardship programs.

SG-APSIC1097: The impact of COVID-19 on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore: An interrupted time-series analysis

Objectives: Over the past 2 years, many infection prevention and control (IPC) resources have been diverted to manage the COVID-19 pandemic. Its impact on the incidence of antimicrobial-resistant organisms has not been adequately studied. We investigated the impact of the pandemic on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore. Methods: We extracted data on unique CRE isolates (clinical and/or surveillance cultures) and patient days for 6 public hospitals in Singapore from the carbapenemase-producing Enterobacteriaceae (CaPES) study group database, and we calculated the monthly incidence of CRE (per 10,000 patient days). Interrupted time-series (ITS) analysis was conducted with the pre–COVID-19 period defined as before February 2020, and the COVID-19 period defined as after February 2020. Statistical analyses were performed using Stata version 15 software. Results: From January 2017 to March 2021, 6,770 CRE isolates and 9,126,704 patient days were documented. The trend in CRE monthly incidence increased significantly during the pre–COVID-19 period (0.060;95% CI, 0.033–0.094;P < .001) but decreased during the COVID-19 period (−0.183;95% CI, −0.390 to 0.023;P = .080) without stepwise change in the incidence (−1.496;95% CI, −3.477 to 0.485;P = .135). The trend in monthly incidence rate of CRE clinical cultures increased significantly during the pre–COVID-19 period (0.046;95% CI, 0.028–0.064;P < .001) and decreased significantly during COVID-19 period (−0.148;95% CI, −0.249 to −0.048;P = .048) with no stepwise change in the incidence (−0.063;95% CI, −0.803 to 0.677;P = .864). The trend in monthly incidence rate of CRE surveillance cultures decreased during the pre–COVID-19 period (−0.020;95% CI, −0.062 to 0.022;P = .341) and the COVID-19 period (−0.067;95% CI, −0.291to 0.158;P = .552) without stepwise change in the incidence (−1.327;95% CI, −3.535 to 0.881;P = .233). Conclusions: The rate of CRE in clinical cultures decreased during COVID-19 but not the rate in surveillance cultures. Further studies are warranted to study the impact of COVID-19 on CREs.(DUPLICATE DELETED)

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.

Factors associated with the opposition to COVID-19 vaccination certificates: A multi-country observational study from Asia.

BACKGROUND: There are ongoing calls to harmonise and increase the use of COVID-19 vaccination certificates (CVCs) in Asia. Identifying groups in Asian societies who oppose CVCs and understanding their reasons can help formulate an effective CVCs policy in the region. However, no formal studies have explored this issue in Asia. METHOD: The COVID-19 Vaccination Policy Research and Decision-Support Initiative in Asia (CORESIA) was established to address policy questions related to CVCs. An online cross-sectional survey was conducted from June to October 2021 in nine Asian countries. Multivariable logistical regression analyses were performed to identify potential opposers of CVCs. RESULTS: Six groups were identified as potential opposers of CVCs: (i) unvaccinated (Odd Ratio (OR): 2.01, 95% Confidence Interval (CI): 1.65-2.46); vaccine hesitant and those without access to COVID-19 vaccines; (ii) those not wanting existing NPIs to continue (OR: 2.97, 95% CI: 2.51-3.53); (iii) those with low level of trust in governments (OR: 1.25, 95% CI: 1.02-2.52); (iv) those without travel plans (OR: 1.58, 95% CI: 1.31-1.90); (v) those expecting no financial gains from CVCs (OR: 2.35, 95% CI: 1.98-2.78); and (vi) those disagreeing to use CVCs for employment, education, events, hospitality, and domestic travel. CONCLUSIONS: Addressing recurring public health bottlenecks such as vaccine hesitancy and equitable access, adherence to policies, public trust, and changing the narrative from 'societal-benefit' to 'personal-benefit' may be necessary and may help increase wider adoption of CVCs in Asia.

Contrasting SARS-CoV-2 epidemics in Singapore: cohort studies in migrant workers and the general population.

IMPORTANCE: Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories. OBJECTIVE: To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore. DESIGN: Prospective serological cohort studies. SETTING: Two cohort studies - in a migrant worker dormitory and in the general population in Singapore. PARTICIPANTS: 478 residents of a SARS-CoV-2-affected migrant worker dormitory were followed up between May and July 2020, with blood samples collected on recruitment and after 2 and 6 weeks. In addition, 937 community-dwelling adult Singapore residents, for whom pre-pandemic sera were available, were recruited. These individuals also provided a serum sample on recruitment in November/December 2020. EXPOSURE: Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population. MAIN OUTCOMES AND MEASURES: The main outcome measures were the incidences of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralizing antibodies against SARS-CoV-2, and adjusting for assay sensitivity and specificity using a Bayesian modeling framework. RESULTS: No evidence of community SARS-CoV-2 exposure was found in Singapore prior to September 2019. It was estimated that < 2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16%; 95% CrI: 0.008-0.72%). Comparison with comprehensive national case notification data suggested that around 1 in 4 infections in the general population were associated with symptoms. In contrast, in the migrant worker cohort, almost two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8%; 95% CrI: 57.9-70.3%); no symptoms were reported in almost all of these infections. CONCLUSIONS AND RELEVANCE: Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining, and social-distancing measures. However, the risk of large-scale epidemics in densely populated environments requires specific consideration in preparedness planning. Prioritization of these settings in vaccination strategies should minimize the risk of future resurgences and potential spillover of transmission to the wider community.

Widely heterogeneous humoral and cellular immunity after mild SARS-CoV-2 infection in a homogeneous population of healthy young men.

BACKGROUND: We studied humoral and cellular responses against SARS-CoV-2 longitudinally in a homogeneous population of healthy young/middle-aged men of South Asian ethnicity with mild COVID-19. METHODS: In total, we recruited 994 men (median age: 34 years) post-COVID-19 diagnosis. Repeated cross-sectional surveys were conducted between May 2020 and January 2021 at six time points - day 28 (n = 327), day 80 (n = 202), day 105 (n = 294), day 140 (n = 172), day 180 (n = 758), and day 280 (n = 311). Three commercial assays were used to detect anti-nucleoprotein (NP) and neutralizing antibodies. T cell response specific for Spike, Membrane and NP SARS-CoV-2 proteins was tested in 85 patients at day 105, 180, and 280. RESULTS: All serological tests displayed different kinetics of progressive antibody reduction while the frequency of T cells specific for different structural SARS-CoV-2 proteins was stable over time. Both showed a marked heterogeneity of magnitude among the studied cohort. Comparatively, cellular responses lasted longer than humoral responses and were still detectable nine months after infection in the individuals who lost antibody detection. Correlation between T cell frequencies and all antibodies was lost over time. CONCLUSION: Humoral and cellular immunity against SARS-CoV-2 is induced with differing kinetics of persistence in those with mild disease. The magnitude of T cells and antibodies is highly heterogeneous in a homogeneous study population. These observations have implications for COVID-19 surveillance, vaccination strategies, and post-pandemic planning.

Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals.

Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein-specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1-convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike-specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.

Strengthening national capacities for pandemic preparedness: a cross-country analysis of COVID-19 cases and deaths.

The International Health Regulations-State Party Annual Reporting (IHR-SPAR) index and the Global Health Security Index (GHSI) have been developed to aid in strengthening national capacities for pandemic preparedness. We examined the relationship between country-level rankings on these two indices, along with two additional indices (the Universal Health Coverage Service Coverage Index and World Bank Worldwide Governance Indicator (n = 195)) and compared them to the country-level reported coronavirus disease (COVID-19) cases and deaths (Johns Hopkins University COVID-19 Dashboard) through 17 June 2020. Ordinary least squares regression models were used to compare weekly reported COVID-19 cases and death rates per million in the first 12 weeks of the pandemic between countries classified as low, middle and high ranking on each index while controlling for country socio-demographic information. Countries with higher GHSI and IHR-SPAR index scores experienced fewer reported COVID-19 cases and deaths but only for the first 8 weeks after the country's first case. For the GHSI, this association was further limited to countries with populations below 69.4 million. For both the GHSI and IHR-SPAR, countries with a higher sub-index score in human resources for pandemic preparedness reported fewer COVID-19 cases and deaths in the first 8 weeks after the country's first reported case. The Universal Health Coverage Service Coverage Index and Worldwide Governance Indicator country-level rankings were not associated with COVID-19 outcomes. The associations between GHSI and IHR-SPAR scores and COVID-19 outcomes observed in this study demonstrate that these two indices, although imperfect, may have value, especially in countries with a population under 69.4 million people for the GHSI. Preparedness indices may have value; however, they should continue to be evaluated as policy makers seek to better prepare for future global public health crises.

Correction to: The Perfect Moral Storm: Diverse Ethical Considerations in the COVID-19 Pandemic.

[This corrects the article DOI: 10.1007/s41649-020-00125-3.].

Updated APLAR consensus statements on care for patients with rheumatic diseases during the COVID-19 pandemic.

AIM: To update previous guidance of the Asia Pacific League of Associations for Rheumatology (APLAR) on the management of patients with rheumatic and musculoskeletal diseases (RMD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Research questions were formulated focusing on diagnosis and treatment of adult patients with RMD within the context of the pandemic, including the management of RMD in patients who developed COVID-19. MEDLINE was searched for eligible studies to address the questions, and the APLAR COVID-19 task force convened 2 meetings through video conferencing to discuss its findings and integrate best available evidence with expert opinion. Consensus statements were finalized using the modified Delphi process. RESULTS: Agreement was obtained around key aspects of screening for or diagnosis of COVID-19; management of patients with RMD without confirmed COVID-19; and management of patients with RMD with confirmed COVID-19. The task force achieved consensus on 25 statements covering the potential risk of acquiring COVID-19 in RMD patients, advice on RMD medication adjustment and continuation, the roles of telemedicine and vaccination, and the impact of the pandemic on quality of life and on treatment adherence. CONCLUSIONS: Available evidence primarily from descriptive research supported new recommendations for aspects of RMD care not covered in the previous document, particularly with regard to risk factors for complicated COVID-19 in RMD patients, modifications to RMD treatment regimens in the context of the pandemic, and COVID-19 vaccination in patients with RMD.

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection.

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2-specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2-specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1ß) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2-infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

Saliva is more sensitive than nasopharyngeal or nasal swabs for diagnosis of asymptomatic and mild COVID-19 infection.

We aimed to test the sensitivity of naso-oropharyngeal saliva and self-administered nasal (SN) swab compared to nasopharyngeal (NP) swab for COVID-19 testing in a large cohort of migrant workers in Singapore. We also tested the utility of next-generation sequencing (NGS) for diagnosis of COVID-19. Saliva, NP and SN swabs were collected from subjects who presented with acute respiratory infection, their asymptomatic roommates, and prior confirmed cases who were undergoing isolation at a community care facility in June 2020. All samples were tested using RT-PCR. SARS-CoV-2 amplicon-based NGS with phylogenetic analysis was done for 30 samples. We recruited 200 subjects, of which 91 and 46 were tested twice and thrice respectively. In total, 62.0%, 44.5%, and 37.7% of saliva, NP and SN samples were positive. Cycle threshold (Ct) values were lower during the earlier period of infection across all sample types. The percentage of test-positive saliva was higher than NP and SN swabs. We found a strong correlation between viral genome coverage by NGS and Ct values for SARS-CoV-2. Phylogenetic analyses revealed Clade O and lineage B.6 known to be circulating in Singapore. We found saliva to be a sensitive and viable sample for COVID-19 diagnosis.

COVID-19 and Singapore: From Early Response to Circuit Breaker.

Singapore, an island country with 5.6 million population and a large volume of tourists from mainland China, was one of the first countries to report imported COVID-19 cases and had the highest number of cases outside mainland China for a time in February 2020. The government responded with a series of broadscale public health measures and managed to contain this first wave of infection. Notwithstanding that, an evolving pandemic situation in other countries eventually triggered a second, and much larger, wave of infection. This case study narrates the developments, influencing factors, and outcomes related to events starting from Singapore's first response to COVID-19 and up to the point of its entry into Circuit Breaker. It serves as a reference for the understanding and analysis of developments in an evolving pandemic and a nation's response from a systems level perspective.

Lessons learnt from easing COVID-19 restrictions: an analysis of countries and regions in Asia Pacific and Europe.

The COVID-19 pandemic is an unprecedented global crisis. Many countries have implemented restrictions on population movement to slow the spread of severe acute respiratory syndrome coronavirus 2 and prevent health systems from becoming overwhelmed; some have instituted full or partial lockdowns. However, lockdowns and other extreme restrictions cannot be sustained for the long term in the hope that there will be an effective vaccine or treatment for COVID-19. Governments worldwide now face the common challenge of easing lockdowns and restrictions while balancing various health, social, and economic concerns. To facilitate cross-country learning, this Health Policy paper uses an adapted framework to examine the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (ie, Hong Kong [Special Administrative Region], Japan, New Zealand, Singapore, and South Korea) and four in Europe (ie, Germany, Norway, Spain, and the UK). This comparative analysis presents important lessons to be learnt from the experiences of these countries and regions. Although the future of the virus is unknown at present, countries should continue to share their experiences, shield populations who are at risk, and suppress transmission to save lives.

Health system resilience in managing the COVID-19 pandemic: lessons from Singapore.

Singapore, one of the first countries affected by COVID-19, adopted a national strategy for the pandemic which emphasised preparedness through a whole-of-nation approach. The pandemic was well contained initially until early April 2020, when there was a surge in cases, attributed to Singapore residents returning from hotspots overseas, and more significantly, rapid transmission locally within migrant worker dormitories. In this paper, we present the response of Singapore to the COVID-19 pandemic based on core dimensions of health system resilience during outbreaks. We also discussed on the surge in cases in April 2020, highlighting efforts to mitigate it. There was: (1) clear leadership and governance which adopted flexible plans appropriate to the situation; (2) timely, accurate and transparent communication from the government; (3) public health measures to reduce imported cases, and detect as well as isolate cases early; (4) maintenance of health service delivery; (5) access to crisis financing; and (6) legal foundation to complement policy measures. Areas for improvement include understanding reasons for poor uptake of government initiatives, such as the mobile application for contact tracing and adopting a more inclusive response that protects all individuals, including at-risk populations. The experience in Singapore and lessons learnt will contribute to pandemic preparedness and mitigation in the future.