Effectiveness of BNT162b2 Vaccine against Omicron in Children 5 to 11 Years of Age.

BACKGROUND: Since it was first identified in early November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly and replaced the B.1.617.2 (delta) variant as the dominant variant in many countries. Data on the real-world effectiveness of vaccines against the omicron variant in children are lacking. METHODS: In a study conducted from January 21, 2022, through April 8, 2022, when the omicron variant was spreading rapidly, we analyzed data on children in Singapore who were 5 to 11 years of age. We assessed the incidences of all reported SARS-CoV-2 infections (confirmed on polymerase-chain-reaction [PCR] assay, rapid antigen testing, or both), SARS-CoV-2 infections confirmed on PCR assay, and coronavirus disease 2019 (Covid-19)-related hospitalizations among unvaccinated, partially vaccinated (≥1 day after the first dose of vaccine and up to 6 days after the second dose), and fully vaccinated children (≥7 days after the second dose). Poisson regression was used to estimate vaccine effectiveness from the incidence rate ratio of outcomes. RESULTS: A total of 255,936 children were included in the analysis. Among unvaccinated children, the crude incidence rates of all reported SARS-CoV-2 infections, PCR-confirmed SARS-CoV-2 infections, and Covid-19-related hospitalizations were 3303.5, 473.8, and 30.0 per 1 million person-days, respectively. Among partially vaccinated children, vaccine effectiveness was 13.6% (95% confidence interval [CI], 11.7 to 15.5) against all SARS-CoV-2 infections, 24.3% (95% CI, 19.5 to 28.9) against PCR-confirmed SARS-CoV-2 infection, and 42.3% (95% CI, 24.9 to 55.7) against Covid-19-related hospitalization; in fully vaccinated children, vaccine effectiveness was 36.8% (95% CI, 35.3 to 38.2), 65.3% (95% CI, 62.0 to 68.3), and 82.7% (95% CI, 74.8 to 88.2), respectively. CONCLUSIONS: During a period when the omicron variant was predominant, BNT162b2 vaccination reduced the risks of SARS-CoV-2 infection and Covid-19-related hospitalization among children 5 to 11 years of age.

Long-term Cardiovascular, Cerebrovascular, and Other Thrombotic Complications in COVID-19 Survivors: A Retrospective Cohort Study.

BACKGROUND: Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian population, during Delta predominance. METHODS: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals who had a positive SARS-CoV-2 test between 1 September and 30 November 2021 when Delta predominated community transmission. Concurrently, we constructed a test-negative control group by enrolling individuals between 13 April 2020 and 31 December 2022 with no evidence of SARS-CoV-2 infection. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular, cerebrovascular, and other thrombotic complications using doubly robust competing-risks survival analysis. Risks were reported using 2 measures: hazard ratio (HR) and excess burden (EB) with 95% confidence intervals. RESULTS: We included 106 012 infected cases and 1 684 085 test-negative controls. Compared with the control group, individuals with COVID-19 exhibited increased risk (HR, 1.157 [1.069-1.252]) and excess burden (EB, 0.70 [.53-.88]) of new-incident cardiovascular and cerebrovascular complications. Risks decreased in a graded fashion for fully vaccinated (HR, 1.11 [1.02-1.22]) and boosted (HR, 1.10 [.92-1.32]) individuals. Conversely, risks and burdens of subsequent cardiovascular/cerebrovascular complications increased for hospitalized and severe COVID-19 cases (compared to nonhospitalized cases). CONCLUSIONS: Increased risks and excess burdens of new-incident cardiovascular/cerebrovascular complications were reported among infected individuals; risks can be attenuated with vaccination and boosting.

Risks of SARS-CoV-2 JN.1 infection and COVID-19 associated emergency-department (ED) visits/hospitalizations following updated boosters and prior infection: a population-based cohort study.

INTRODUCTION: Data on protection afforded by updated COVID-19 vaccines (bivalent/XBB 1.5 monovalent) against the emergent JN.1 variant remains limited. METHODS: We conducted a retrospective population-based cohort study amongst all boosted Singaporeans aged ≥18 years during a COVID-19 wave predominantly driven by JN.1, from 26th November 2023 to 13th January 2024. Multivariable Cox regression was utilised to assess risk of SARS-CoV-2 infection and COVID-19 associated emergency-department (ED) visits/hospitalizations, stratified by vaccination status/prior infection; with individuals last boosted ≥1 year utilized as the reference category. Vaccination and infection status were classified using national registries. RESULTS: 3,086,562 boosted adult Singaporeans were included in the study population, accounting for 146,863,476 person-days of observation. During the JN.1 outbreak, 28,160 SARS-CoV-2 infections were recorded, with 2,926 hospitalizations and 3,747 ED-visits. Compared with individuals last boosted ≥1 year prior with ancestral monovalent vaccines, receipt of an updated XBB.1.5 booster 8-120 days prior was associated with lower risk of JN.1 infection (adjusted-hazard-ratio, aHR = 0.59[0.52-0.66]), COVID-19 associated ED-visits (aHR = 0.50[0.34-0.73]) and hospitalizations(aHR = 0.58[0.37-0.91]), while receipt of a bivalent booster 121-365 days prior was associated with lower risk of JN.1 infection (aHR = 0.92[0.88-0.95]) and ED-visits (aHR = 0.80[0.70-0.90]). Lower risk of COVID-19 hospitalization during the JN.1 outbreak (aHR = 0.57[0.33-0.97]) was still observed following receipt of an updated XBB.1.5 booster 8-120 days prior, even when analysis was restricted to previously infected individuals. CONCLUSION: Recent receipt of updated boosters conferred protection against SARS-CoV-2 infection and ED-visits/hospitalization during a JN.1 variant wave, in both previously infected and uninfected individuals. Annual booster doses confer protection during COVID-19 endemicity.

Long-term Real-world Protection Afforded by Third mRNA Doses Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections, Coronavirus Disease 19-related Emergency Attendances and Hospitalizations Amongst Older Singaporeans During an Omicron XBB Wave.

BACKGROUND: Literature on long-term real-world vaccine effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster vaccines (up to and beyond 360 days) is scarce. We report estimates of protection against symptomatic infection, emergency department (ED) attendances and hospitalizations up to and beyond 360 days post-receipt of booster messenger RNA (mRNA) vaccines among Singaporeans aged ≥60 years during an Omicron XBB wave. METHODS: We conducted a population-based cohort study including all Singaporeans aged ≥60 years with no documented prior SARS-CoV-2 infection who had previously received ≥3 doses of mRNA vaccines (BNT162b2/mRNA-1273), over a 4-month period during transmission of Omicron XBB. We reported the adjusted incidence-rate-ratio (IRR) for symptomatic infections, ED attendances and hospitalizations at different time-intervals from both first and second boosters, using Poisson regression; with the reference group being those who received their first booster 90 to 179 days prior. RESULTS: In total, 506 856 boosted adults were included, contributing 55 846 165 person-days of observation. Protection against symptomatic infections among those who received a third vaccine dose (first booster) waned after 180 days with increasing adjusted IRRs; however, protection against ED attendances and hospitalizations held up, with comparable adjusted IRRs with increasing time from third vaccine doses (≥360 days from third dose: adjusted IRR [ED attendances] = 0.73, 95% confidence interval [CI] = .62-.85; adjusted IRR [hospitalization] = 0.58, 95% CI = .49-.70). CONCLUSIONS: Our results highlight the benefit of a booster dose in reducing ED attendances and hospitalizations amongst older adults aged ≥60 years with no documented prior SARS-CoV-2 infection, during an Omicron XBB wave; up to and beyond 360 days post-booster. A second booster provided further reduction.

Comparative Effectiveness of mRNA and Inactivated Whole-Virus Vaccines Against Coronavirus Disease 2019 Infection and Severe Disease in Singapore.

Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29-2.46) and 1.62 (95% CI, 1.43-1.85) times more likely to be infected with coronavirus disease 19, respectively, while individuals vaccinated with Moderna were 0.42 (95% CI, 0.25-0.70) times less likely to develop severe disease.

A case of immune-mediated encephalitis related to daclizumab therapy.

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Systems approaches for localising the SDGs: co-production of place-based case studies.

BACKGROUND: Localisation is a pervasive challenge in achieving sustainable development. Contextual particularities may render generalized strategies to achieve the Sustainable Development Goals (SDGs) unfeasible, impractical, or ineffective. Furthermore, many localities are resource- and data-poor, limiting applicability of the global SDG indicator framework. Tools to enable local actors to make sense of complex problems, communicate this understanding, and act accordingly hold promise in their ability to improve results. AIM: Systems approaches can help characterise local causal systems, identify useful leverage points, and foster participation needed to localise and catalyse development action. Critically, such efforts must be deeply rooted in place, involving local actors in mapping decision-processes and causation within local physical, social and policy environments. Given that each place has a unique geographical or spatial extent and therein lies its unique characters and problems, we term these activities "placially explicit." We describe and reflect on a process used to develop placially explicit, systems-based (PESB) case studies on issues that intersect with and impact urban health and wellbeing, addressing the perspectives of various actors to produce place-based models and insights that are useful for SDG localisation. METHODS: Seven case studies were co-produced by one or more Partners with place-based knowledge of the case study issue and a Systems Thinker. In each case, joint delineation of an appropriate framing was followed by iterative dialogue cycles to uncover key contextual factors, with attention to institutional and societal structures and paradigms and the motivations and constraints of other actors. Casual loop diagrams (CLDs) were iteratively developed to capture complex narratives in a simple visual way. RESULTS: Case study development facilitated transfer of local knowledge and development of systems thinking capacity. Partners reported new insights, including a shifting of problem frames and corresponding solution spaces to higher systems levels. Such changes led partners to re-evaluate their roles and goals, and thence to new actions and strategies. CLD-based narratives also proved useful in ongoing communications. CONCLUSION: Co-production of PESB case studies are a useful component of transdisciplinary toolsets for local SDG implementation, building the capacity of local actors to explore complex problems, identify new solutions and indicators, and understand the systemic linkages inherent in SDG actions across sectors and scales.

Predictors for secondary therapy after surgical resection of nonfunctioning pituitary adenomas.

OBJECTIVE: Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow-up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management. DESIGN AND PATIENTS: A single-centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years. Serial tumour images were analysed for size, location and growth rate (GR) and tissue analysed for hormone cell type and proliferation indices with secondary treatment as outcome measure. RESULTS: Twenty-four of 66 (36%) patients harbouring a postoperative remnant required secondary treatment, all occurring within 10 years. No secondary treatment was required in any of 42 patients with complete tumour resection. Age, gender, remnant volume and tumour histology were not different between patients requiring and not requiring secondary therapy. Remnant GRs in those requiring secondary therapy were more than 10-fold higher (P<.01). Tumours with a GR ≥80 mm3 /y (Hazard Ratio[HR]: 8.1, Confidence Interval [CI]: 2.4-27.3,P<.01) and those located in the suprasellar region (HR: 6.1, CI: 1.1-32, P=.03) had a higher risk for secondary therapy. Tumour GR in the first three postoperative years correlated significantly (r2 =.6, P<.01) with GR during the period of follow-up. CONCLUSION: In surgically resected NFAs further treatment is dependent on the presence of residual tumour, growth rate and location but not tumour histology. Postoperative growth rate of NFAs in the first 3 years of imaging can be used to tailor long-term follow-up to optimize use of health resources.

Singapore's regional health systems-a data-driven perspective on frequent admitters and cross utilization of healthcare services in three systems.

INTRODUCTION: With population health management being a priority in the Singapore, this paper aims to provide a data-driven perspective of the population health management initiatives to aid program planning and serves as a baseline for evaluation of future implemented programs. METHODS: A database with information on patient demographics, health services utilization, cost, diagnoses and chronic disease information from 2008 to 2013 for three regional health systems in Singapore was used for analysis. Patients with three or more inpatient admissions were considered as "Frequent Admitters." Health service utilization was quantified, and cross utilization of services was studied. One-year readmission rate for inpatients was studied, and a predictive model for readmission or death was developed. RESULTS: There were a total of 2.8 M patients in the database. Frequent admitters accounted for 0.9% of all patients with an average cost per patient of S$29 547. Of these, 89% had chronic diseases. Cross utilization of health services showed that 8.2% of the patients utilized services from more than one hospital with 19.6% utilizing hospital and polyclinic services in 2013. The highest risk of readmission or death was for those patients who had five or more inpatient episodes in each of the preceding 2 years. CONCLUSION: By understanding the profile of the patients and their utilization patterns in the three regional health systems, our study will help clinicians and decision makers design appropriate integrated care programs for patients with the aim of covering the healthcare needs for the enitre population across the healthcare spectrum in Singapore. Copyright © 2015 John Wiley & Sons, Ltd.

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.

The antimalarial drug artesunate inhibits primary human cultured airway smooth muscle cell proliferation.

Airway smooth muscle (ASM) cell hyperplasia contributes to airway wall remodeling (AWR) in asthma. Glucocorticoids, which are used as first-line therapy for the treatment of inflammation in asthma, have limited impact on AWR, and protracted usage of high doses of glucocorticoids is associated with an increased risk of side effects. Moreover, patients with severe asthma often show reduced sensitivity to glucocorticoids. Artesunate, a semisynthetic artemisinin derivative used to treat malaria with minimal toxicity, attenuates allergic airway inflammation in mice, but its impact on AWR is not known. We examined the effects of artesunate on ASM proliferation in vitro and in vivo. Primary human ASM cells derived from nonasthmatic donors were treated with artesunate before mitogen stimulation. Artesunate reduced mitogen-stimulated increases in cell number and cyclin D1 protein abundance but had no significant effect on ERK1/2 phosphorylation. Artesunate, but not dexamethasone, inhibited phospho-Akt and phospho-p70(S6K) protein abundance. Artesunate, but not dexamethasone, inhibited mitogen-stimulated increases in cell number, cyclin D1, and phospho-Akt protein abundance on ASM cells derived from asthmatic donors. In a murine model of allergic asthma, artesunate reduced the area of α-smooth muscle actin-positive cells and decreased cyclin D1 protein abundance. Our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt/p70(S6K) pathway and suggests that artesunate may be used as combination therapy with glucocorticoids.

Cost-utility analysis of sacituzumab govitecan versus chemotherapy for the treatment of metastatic triple-negative breast cancer in Singapore.

OBJECTIVE: To assess the cost-effectiveness of sacituzumab govitecan for treating relapsed or refractory metastatic triple-negative breast cancer (TNBC) in Singapore. METHODS: A three-state partitioned survival model was developed to evaluate the cost-effectiveness of sacituzumab govitecan from a healthcare system perspective over 5 years. Clinical inputs were obtained from the ASCENT trial. Health state utilities were retrieved from the literature and direct costs were sourced from public healthcare institutions in Singapore. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with single-agent chemotherapy, sacituzumab govitecan was associated with a base-case incremental cost-effectiveness ratio (ICER) of S$328,000 (US$237,816) per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that the ICER was most sensitive to the cost of sacituzumab govitecan and progression-free utility values. Regardless of variation in these parameters, the ICER remained high, and a substantial price reduction was required to reduce the ICER. CONCLUSION: At its current price, sacituzumab govitecan does not represent a cost-effective treatment for relapsed or refractory metastatic TNBC in Singapore. Our findings will be useful to inform funding decisions alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Long-term neuropsychiatric sequelae of Delta versus Omicron SARS-CoV-2 infection.

OBJECTIVES: Studies have reported increased rates of long-term neuropsychiatric sequelae after SARS-CoV-2 infection using electronic health-record (EHR) data; however, the majority were conducted before Omicron and booster rollout. We estimated the long-term risks and excess burdens of pre-specified new-incident neuropsychiatric diagnoses after Delta versus Omicron BA.1/2 infection in a highly-vaccinated and boosted cohort of adult Singaporeans. METHODS: The national SARS-CoV-2 testing registry was used to construct cohorts of Singaporean adults infected during periods of Delta and Omicron BA.1/2 predominance and a contemporaneous test-negative control group. New-incident neuropsychiatric diagnoses recorded in the national health care claims database were identified up to 300 days postinfection. Risks and excess burden were estimated using a doubly robust competing-risks survival analysis. RESULTS: 104 179 and 375 903 infected cases were assigned to Delta and Omicron cohorts and compared against test-negative controls (Delta: N = 666 575 and Omicron: N = 619 379). Elevated risk of cognition or memory disorders was consistently reported across Omicron (Adjusted hazards ratio [aHR], 1.24; 95% CI, 1.12-1.38) and Delta cohorts (aHR, 1.63; 95% CI, 1.39-1.92). Delta-variant infection was associated with an increased risk of anosmia or dysgeusia (aHR, 4.53; 95% CI, 2.78-7.41) and psychosis (aHR, 1.65; 95% CI, 1.22-2.22). By contrast, Omicron-variant infection was associated with a risk of abnormal involuntary movements (aHR, 1.93; 95% CI, 1.32-2.83). Risks of neuropsychiatric sequelae predominantly accrued in hospitalized individuals. DISCUSSIONS: A modestly increased risk of cognition and memory disorders at 300 days after SARS-CoV-2 infection was observed among adult Singaporeans infected during the Delta/Omicron BA.1/2 transmission. There was no overall increased risk of neuropsychiatric sequelae observed across other domains. Variant-specific differences were also observed in individual neuropsychiatric sequelae, including an elevated risk of anosmia or dysgeusia after Delta-variant infection.

Long-term cardiovascular, cerebrovascular, and thrombotic complications after SARS-CoV-2-Omicron infection: a retrospective cohort study.

OBJECTIVES: Evidence suggests that some COVID-19 survivors experience a wide range of post-COVID-19 sequelae; however, the majority of studies were conducted prior to 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.1/2 transmission, and a contemporaneous test-negative group. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular complications using doubly robust competing-risks survival analysis. Risks were reported using two measures: hazard ratio (HR) and excess burden (EB). RESULTS: We included 375,903 test-positive, infected individuals (mean age 48 years) and 619,379 test-negative controls (mean age 47 years). The majority (97.5%, 366,593/375,903) of infected individuals had mild infection not requiring hospitalisation. There was no overall increased risk of new-incident cardiovascular complications, (adjusted-hazards-ratio, aHR = 1.01 [0.97-1.07]) amongst COVID-19 survivors when compared against test-negatives. A modestly increased risk and excess burden of dysrhythmias amongst COVID-19 survivors (aHR=1.09 [1.01- 1.19]) was observed. Risk and burdens of new-incident cardiovascular complications predominantly accrued in hospitalised (aHR=5.52 [3.76-8.10]) and severe (aHR=5.52 [3.76-8.10]) COVID-19 cases. CONCLUSIONS: No significantly increased overall risk of any cardiovascular complication was observed in the 300 days following COVID-19 infection during the Omicron-dominant period when compared against test-negatives, with the exception of a small increased occurrence of dysrhythmias.

Real-world impact of a subsidy decision of sofosbuvir-velpatasvir for treatment of chronic hepatitis C on clinical practice and patient outcomes.

Background and Aim: Sofosbuvir-velpatasvir was recommended for subsidy to treat chronic hepatitis C in Singapore in 2018. We measured the impact of the subsidy decision on clinical practice and patient outcomes. Specifically, we looked at pre- and post-subsidy changes in the utilization and prescribing pattern of chronic hepatitis C treatment and the real-world clinical effectiveness. Method: Utilization trends and prescribing patterns were assessed using aggregated drug utilization data from public hospitals' dispensing systems and clinical data from the national electronic health record database, respectively. An audit was conducted to evaluate sustained virological response rate 12 weeks post treatment (SVR12). Results: Use of sofosbuvir-velpatasvir increased sharply since its subsidy listing and dropped subsequently, whereas the utilization of comparator drugs remained low. Prescribing rate of sofosbuvir-velpatasvir increased from 13.7% in the pre-subsidy period to 90.2% in the post-subsidy period; 39.1% of patients previously on pegylated interferon and ribavirin switched to sofosbuvir-velpatasvir following its subsidy listing. In the audit, 365 out of 375 patients (97.3% [95% confidence interval: 95.1-98.6%]) achieved SVR12. Conclusion: The subsidy decision led to increased accessibility to patients and intended changes in clinical practice. Sofosbuvir-velpatasvir was also clinically effective in the real world. These findings augur well for the continued eradication of chronic hepatitis C infection in Singapore.

Vaccine effectiveness against Delta, Omicron BA.1, and BA.2 in a highly vaccinated Asian setting: a test-negative design study.

OBJECTIVES: We compared the vaccine effectiveness over time of the primary series and booster against infection and severe disease with the Delta, Omicron BA.1, and BA.2 variants in Singapore, an Asian setting with high vaccination coverage. METHODS: We conducted a test-negative case-control study on all adult residents in Singapore who underwent PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute hospitals. Individuals with a negative PCR from 1 September, 2021, to 30 November, 2021, and 1 December, 2021, to 25 April, 2022, served as controls for the Delta and Omicron variants respectively, and PCR-positive individuals within these two time periods served as cases. Associations between vaccination status and SARS-CoV-2 infection and severe disease with the Delta or Omicron variants were measured using Poisson regressions. Vaccine effectiveness was calculated by taking 1 minus risk ratio. RESULTS: There were 68 114 individuals comprising 58 495 controls and 9619 cases for the Delta period, of whom 53 093 completed the primary series and 9161 were boosted. For the Omicron period, 104 601 individuals comprising 80 428 controls, 8643 BA.1 cases, and 15 530 BA.2 cases were included, of whom 29 183 and 71 513 were vaccinated with the primary series and boosted, respectively. The primary series provided greater protection against infection with Delta (45%, 95% CI 40-50%) than against infection with Omicron (21%, 95% CI 7-34% for BA.1; 18%, 95% CI 6-29% for BA.2) at <2 months from vaccination. Vaccine effectiveness of the booster was similar against infection with BA.1 (44%, 95% CI 38-50%) and BA.2 (40%, 95% CI 35-40%). Protection against severe disease by the booster for BA.1 (83%, 95% CI 76-88%) and BA.2 (78%, 95% CI 73-82%) was comparable to that by the primary series for Delta (80%, 95% CI 73-85%). CONCLUSION: Our findings support the use of a booster dose to reduce the risk of severe disease and mitigate the impact on the healthcare system in an Omicron-predominant epidemic.

Effectiveness of primary series and booster vaccination against SARS-CoV-2 infection and hospitalisation among adolescents aged 12-17 years in Singapore: a national cohort study.

BACKGROUND: Singapore offered the BNT162b2 vaccine (tozinameran; Pfizer-BioNTech) to adolescents aged 12-17 years in May 18, 2021, and extended booster vaccines to this group in Jan 21, 2022. Literature on the effectiveness of primary series and booster vaccination among adolescents is scarce outside of Europe and North America. We aimed to determine primary series and booster vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adolescents in Singapore. METHODS: For this national cohort study, we assessed the incidence of confirmed SARS-CoV-2 infection and hospitalisation among adolescents aged 12-17 years vaccinated with BNT162b2 in Singapore from Sept 1 to Dec 15, 2021, during the delta (B.1.617.2) variant wave, and from Jan 21 to April 28, 2022, during the omicron (B.1.1.529) variant wave. Data were collected from official databases maintained by the Ministry of Health of Singapore. Individuals were classified as partly vaccinated (those who had received one dose and those who had received the second dose no more than 7 days previously), fully vaccinated (8 days after receiving a second dose), or boosted (8 days after receiving a third dose) and compared with unvaccinated individuals. FINDINGS: 249 763 individuals aged 12-17 years were included in the study, contributing over 56·2 million person-days of observation. Compared with unvaccinated individuals, two vaccine doses achieved vaccine effectiveness of 66% (95% CI 63-69) against infection with the delta variant and 25% (21-29) against infection with the omicron variant, and 83% (74-89) against delta variant-associated hospitalisation and 75% (56-86) against omicron variant-associated hospitalisation. Booster vaccination with a third dose achieved vaccine effectiveness of 56% (53-58) against infection with the omicron variant and 94% (86-97) against omicron-associated hospitalisation, compared with unvaccinated adolescents. Vaccine effectiveness against infection for both variants after two doses waned over time, whereas vaccine effectiveness against hospitalisation for both variants remained stable; both were increased after three doses. INTERPRETATION: Among adolescents aged 12-17 years, vaccine effectiveness against confirmed SARS-CoV-2 infection after two doses of BNT162b2 decreased over time and increased after a third dose. Boosted adolescents were also the most protected from hospitalisation compared with fully vaccinated, partly vaccinated, and unvaccinated adolescents. Therefore, the booster dose of BNT162b2 can help to reduce the burden on the health-care system and individual morbidity during an omicron wave. FUNDING: None.