Introduction: Contact tracing has been a key tool to contain the spread of diseases and was widely used by countries during the COVID-19 pandemic. However, evaluating the effectiveness of contact tracing has been challenging. Approaches to contact tracing were diverse and country-dependent, with operations utilizing different tracing methods under varied environments. To provide guidance on contact tracing for future preparedness, we assessed the effectiveness of contact tracing methods under varied environments using Singapore's population structure and COVID-19 as the disease model. Methods: We developed a transmission network model using Singapore's contact tracing data and the characteristics of COVID-19 disease. We explored three different tracing methods that could be employed by contact tracing operations: forward tracing, extended tracing and cluster tracing. The forward tracing method covered the period starting two days before case isolation, the extended tracing method covered the period starting 16 days before case isolation, and the cluster tracing method combined forward tracing with cluster identification. Contact tracing operations traced detected cases from surveillance and issued interventions for identified contacts, and we constructed combinations of varied scenarios to replicate variability during pandemic, namely low case-ascertainment or high case-ascertainment and either testing of contacts or quarantine of contacts. We examined the impact of varied contact tracing operations on disease transmission and provider costs. Results: Model simulations showed that the effectiveness of contact tracing methods varied under the four different scenarios. Firstly, under low case-ascertainment with testing of contacts, contact tracing reduced transmission by 12 %–22 %, with provider costs ranging between US$2943.56 to US$5226.82 per infection prevented. The most effective tracing method to control infection was cluster tracing, followed by extended tracing and forward tracing. Secondly, under low case-ascertainment with quarantine of contacts, transmission was reduced by 46 %–62 %, with provider costs below US$4000 per infection prevented. The cluster method reduced transmission by 62 %, enough to bring the reproduction number to close to unity and was the least costly. Extended tracing reduced transmission by 50 % but costed the most, while forward tracing reduced transmission by 46 %. Thirdly, under high case-ascertainment with testing of contacts, the average transmission was reduced by 20 %–26 %, with provider costs to prevent an infection ranging between US$1872.72 to US$3165.09. There was less variability between tracing methods, with cluster tracing reducing transmission the most, followed by extended tracing and forward tracing. Lastly, under high case-ascertainment and quarantine of contacts, contact tracing was the most effective, with provider costs below US$800 per infection prevented. All tracing methods were equally effective in disease containment, bringing the reproduction number below unity and stopping disease transmission early. Discussion: We conclude that contact tracing operated most effectively when implemented with high case-ascertainment rates and quarantine of contacts; disease transmission is stopped early, and the low number of contacts enable tracing operations to be more manageable and less costly. However, the pandemic situation can be dynamic, with fluctuations in resources available for case-ascertainment and quarantine adherence, which can impact the effectiveness of contact tracing. Adapting contact tracing methods to the situation can optimize disease control. Therefore, it is recommended to develop a flexible contact tracing approach that facilitates strategy switching based on resource availability and the skills of tracing operations.

ObjectivesWe aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics.MethodsWe used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into “epidemic quarters”, i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season.ResultsIn all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to six months.ConclusionsThe age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.

Directly transmitted infectious diseases spread through social contacts that change over time, but outbreak models typically make simplifying assumptions about network structure and dynamics. To assess how common assumptions relate to real-world interactions, we analysed 11 networks from five settings and developed metrics, capturing crucial epidemiological features of these networks. We developed a novel metric, the 'retention index', to characterize the distribution of retained contacts over consecutive time steps relative to fully static and dynamic networks. In workplaces and schools, contacts in the same department formed most of the retained contacts. In contrast, no clear contact type dominated the retained contacts in hospitals, thus reducing overall risk of disease introduction would be more effective than control targeted at departments. We estimated the contacts repetition over multiple days and showed that simple resource planning models overestimate the number of unique contacts by 20%-70%. We distinguished the difference between 'superspreader' and infectious individuals driving 'superspreading events' by measuring how often the individual represents the top 80% of contacts in the time steps over the study duration. We showed an inherent difficulty in identifying 'superspreaders' reliably: less than 20% of the individuals in most settings were highly connected for multiple time steps.

Wastewater-based surveillance has been put into practice during the pandemic. Persistence of SARS-CoV-2 in faeces of infected individuals, and high volume of passengers travelling by air, make it possible to detect virus from aircraft wastewater, lending itself to the potential identification of a novel pathogen prior to clinical diagnosis. In this study, we estimated the likelihood of detecting the virus through aircraft wastewater from the probabilities of air travel, viral shedding, defecation, testing sensitivity, and sampling. We considered various hypothetical scenarios, with diverse sampling proportions of inbound flights, surveillance airports, and sources of outbreaks. Our calculations showed that the probability of detecting SARS-CoV-2 would increase exponentially against time in the early phase of the pandemic, and would be much higher if the 20 major airports in Asia, Europe, and North America cooperated to perform aircraft wastewater surveillance. We also found other contributors to early detection, including high sampling proportion of inbound flight at destination airports, small population size of the epicentre relative to the travel volume, and large volume of outbound travelers to major airports around the globe. We concluded that routine aircraft wastewater monitoring could be a feasible approach for early identification and tracking of an emerging pathogen with high faecal shedding rates, particularly when implemented through a global surveillance network of major airports.

Singapore, a highly urbanized island state, has been able to rapidly mobilize public health services to respond to the emergence of SARS-CoV-2. The fast-changing COVID-19 pandemic has posed multiple challenges to the country's response. Despite this, the partnership between the government, the public and private sectors, and the population has enabled Singapore to translate public health strategies into effective response, achieving one of the highest vaccination rates and lowest mortality rates globally. The response mounted in Singapore has drawn heavily on core public health functions and capacities such as surveillance and testing, contact tracing, isolation and quarantine, and vaccination, which were increased and adapted to meet the demands of a rapidly evolving virus and crisis.

Background Matings between male Aedes aegypti mosquitoes infected with wAlbB strain of Wolbachia and wildtype females yield non-viable eggs. We evaluated the efficacy of releasing wAlbB-infected Ae. aegypti male mosquitoes to suppress dengue.Methods We specified the protocol of a two-arm cluster-randomized test-negative controlled trial (cRCT) and emulated it using a nationally representative test-negative/positive database of individuals reporting for febrile illness to any public hospital, general practitioner or polyclinic. We retrospectively built a cohort of individuals who reside in Wolbachia locations vs a comparator control group who do not reside in Wolbachia locations, using a nationally representative database of all individuals whom report for febrile illness and were tested for dengue at the Environmental Health Institute/hospital laboratories/commercial diagnostic laboratories, through general practitioner clinic, polyclinic or public/private hospital from epidemiological week (EW) 1 2019 to EW26 2022. We emulated a constrained randomization protocol used in cRCTs to balance dengue risk between intervention and control arms in the pre-intervention period. We used the inverse probability weighting approach to further balance the intervention and control groups using a battery of algorithmically selected sociodemographic, environmental and anthropogenic variables. Intention-to-treat analyses were conducted to estimate the risk reduction of dengue given Wolbachia exposure.Results Intention-to-treat analyses revealed that, compared with controls, Wolbachia releases for 3, 6 and >= 12 months was associated to 47% (95% confidence interval: 25-69%), 44% (33-77%) and 61% (38-78%) protective efficacy against dengue, respectively. When exposed to >= 12 months of Wolbachia releases, protective efficacies ranged from 49% (13-72%) to 77% (60-94%) across years. The proportion of virologically confirmed dengue cases was lower overall in the intervention arm. Protective efficacies were found across all years, age and sex subgroups, with higher durations of Wolbachia exposure associated to greater risk reductions of dengue.Conclusion Results demonstrated that Wolbachia-mediated sterility can strengthen dengue control in tropical cities, where dengue burden is the greatest.

Importance: Assessing population-wide risk-benefit ratio of COVID-19 vaccination remains relevant in the current era of Omicron endemicity and boosting. Assessments of mortality risk and cardiovascular events post-vaccination/infection were generally made prior to emergence of milder Omicron and booster rollout. Methods: Retrospective cohort study from 6th January to 31st December 2022 (Omicron-predominant transmission), amongst adult Singaporeans aged >= 18 years. Cox regression models adjusted for demographics/comorbidities were used to estimate risk of all-cause mortality and cardiovascular events 0-180 days post-mRNA vaccination/SARS-CoV-2 infection, compared to >180 days post-mRNA vaccination. Risk periods post-vaccination were further stratified by presence/absence of SARS-CoV-2 infection in the preceding 180 days; similarly, risk periods post-infection were further stratified by vaccination in the 180 days preceding infection. Results: 3,137,210 adults participated, with 2,047,008 vaccine doses administered (99 % being booster doses) and 1,189,846 infections. 23,028 deaths and 54,017 cardiac events were recorded. No elevated risk of all-cause mortality/cardiovascular events was observed across all age strata post-vaccination. Conversely, all-cause mortality post-infection remained elevated up to >180 days in older adults (>= 60 years), compared to person-time > 180 days post-vaccination. For vaccine-breakthrough SARS-CoV-2 infection in older adults vaccinated <180 days prior, risk of mortality was only elevated up to 60 days post-infection, but not beyond. Elevated risk of cardiovascular events 1-2 months after any SARS-CoV-2 infection was observed across all age strata, with elevated risk observed in older adults >180 days post-infection (adjusted-hazards-ratio, aHR = 1.18, 95 %CI = 1.04-1.34). Preceding vaccination within 180 days prior to infection attenuated this risk, with no significantly elevated post-acute risk of cardiovascular events (>180 days: aHR = 1.10, 95 %CI = 0.95-1.07). Conclusion: No increased risk of all-cause mortality or cardiovascular events was observed up to 180 days after any mRNA vaccination dose in the Omicron era; vaccination attenuated post-acute cardiovascular risk in older adults. The risk-benefit ratio of vaccination remained positive during Omicron.

Wastewater testing of SARS-CoV-2 has been adopted globally and has shown to be a useful, non-intrusive surveillance method for monitoring COVID-19 trends. In Singapore, wastewater surveillance has been widely implemented across various sites and has facilitated timely COVID-19 management and response.From April 2020 to February 2022, SARS-CoV-2 RNA concentrations in wastewater monitored across three populations, nationally, in the community, and in High Density Living Environments (HDLEs) were aggregated into indices and compared with reported COVID-19 cases and hospitalisations. Temporal trends and associations of these indices were compared descriptively and quantitatively, using Poisson Generalised Linear Models and Generalised Additive Models. National vaccination rates and vaccine breakthrough infection rates were additionally considered as confounders to shedding. Fitted models quantified the temporal associations between the indices and cases and COVID-related hospitalisations.At the national level, the wastewater index was a leading indicator of COVID-19 cases (p-value <0.001) of one week, and a contemporaneous association with hospitalisations (p-value <0.001) was observed. At finer levels of surveillance, the community index was observed to be contemporaneously associated with COVID-19 cases (p value <0.001) and had a lagging association of 1-week in HDLEs (p-value <0.001). These temporal differences were attributed to differences in testing routines for different sites during the study period and the timeline of COVID-19 progression in infected persons. Overall, this study demonstrates the utility of wastewater surveillance in understanding underlying COVID-19 transmission and shedding levels, particularly for areas with falling or low case ascertainment. In such settings, wastewater surveillance showed to be a lead indicator of COVID-19 cases. The findings also underscore the potential of wastewater surveillance for monitoring other infectious diseases threats.

Despite decades of advances in clinical management protocols and new antibiotics, pneumonia continues to be a leading cause of morbidity and mortality worldwide. The 2019 Global Burden of Disease Study indicated that lower respiratory infections, including pneumonia, were the fourth leading cause of disability-adjusted life-years across all ages. 1 Vos T Lim SS Abbafati C et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396: 1204-1222 Summary Full Text Full Text PDF PubMed Scopus (6069) Google Scholar People at the extremes of age, specifically children younger than 10 years and older adults (aged ≥75 years), had the highest burden of lower respiratory infections. 1 Vos T Lim SS Abbafati C et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396: 1204-1222 Summary Full Text Full Text PDF PubMed Scopus (6069) Google Scholar Pneumonia can be broadly divided into community-acquired pneumonia and hospital-acquired pneumonia, of which ventilator-associated pneumonia forms a subset. A substantial proportion of adult patients with community-acquired pneumonia require intensive care management due to severe disease and complications; 2 Jain S Self WH Wunderink RG et al. Community-acquired pneumonia requiring hospitalization among US adults. N Engl J Med. 2015; 373: 415-427 Crossref PubMed Scopus (1479) Google Scholar and in-hospital mortality rates for severe community-acquired pneumonia in adults range from 20% to 30%. 3 Ferrer M Travierso C Cilloniz C et al. Severe community-acquired pneumonia: characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS One. 2018; 13e0191721 Crossref Scopus (60) Google Scholar To guide the management of severe community-acquired pneumonia, international consensus guidelines have recently been published. 4 Martin-Loeches I Torres A Nagavci B et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Intensive Care Med. 2023; 49: 615-632 Crossref PubMed Scopus (17) Google Scholar However, knowledge gaps remain in the treatment of pneumonia that should be addressed through targeted research. In this Comment, we highlight key unaddressed questions and priorities for research (panel). PanelOngoing studies on the management of pneumonia * Not an exhaustive list but some important areas of ongoing research. *Not an exhaustive list but some important areas of ongoing research.Reducing antibiotic treatment duration for pneumonia •Short-course antibiotic therapy of 5 days in community-acquired pneumonia (CAP5; NCT04089787) •Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP; NCT03382548) •The duration of antibiotic therapy for early ventilator associated pneumonia (DATE): 4 days versus 7 days (NCT05545735) •Effect of steroids on outcomes in severe pneumonia: •Arrest respiratory failure from pneumonia (ARREST; NCT04193878) Biomarkers and pneumonia •Diagnostic and prognostic biomarkers for childhood bacterial pneumonia (NCT03996967) Rapid diagnostics in pneumonia: •Trial on a strategy combining rapid diagnostic testing and antimicrobial stewardship to improve antibiotic use in patients with hospital-acquired pneumonia (SHARP; NCT04153682) Combined use of biomarkers and rapid diagnostics in pneumonia •Combined use of a respiratory broad-panel multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP; NCT03452826) Reducing antibiotic treatment duration for pneumonia •Short-course antibiotic therapy of 5 days in community-acquired pneumonia (CAP5; NCT04089787) •Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP; NCT03382548) •The duration of antibiotic therapy for early ventilator associated pneumonia (DATE): 4 days versus 7 days (NCT05545735) •Effect of steroids on outcomes in severe pneumonia: •Arrest respiratory failure from pneumonia (ARREST; NCT04193878) Biomarkers and pneumonia •Diagnostic and prognostic biomarkers for childhood bacterial pneumonia (NCT03996967) Rapid diagnostics in pneumonia: •Trial on a strategy combining rapid diagnostic testing and antimicrobial stewardship to improve antibiotic use in patients with hospital-acquired pneumonia (SHARP; NCT04153682) Combined use of biomarkers and rapid diagnostics in pneumonia •Combined use of a respiratory broad-panel multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP; NCT03452826)

Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed no difference in the severity of different XBB variants.

Importance Literature on vaccine effectiveness of SARS-CoV-2 messenger RNA (mRNA) vaccines for children younger than 5 years is limited.Objective To report the effectiveness of monovalent mRNA vaccines against SARS-CoV-2 infection among Singaporean children aged 1 through 4 years during a COVID-19 pandemic wave of the Omicron XBB variant.Design, Setting, and Participants This was a population-based cohort study, conducted over a 6-month study period from October 1, 2022, through March 31, 2023, after the implementation of community vaccination among all Singaporean children aged 1 through 4 years. The study period was dominated by the Omicron XBB subvariant.Exposure Receipt of SARS-CoV-2 mRNA vaccines.Main Outcome Measure Vaccine effectiveness against confirmed SARS-CoV-2 infection. The adjusted incidence rate ratio for confirmed infections using Poisson regression was reported, with the reference group being those who were unvaccinated. Analyses were stratified by prior documented SARS-CoV-2 infection.Results A total of 121 628 children (median [IQR] age, 3.1 [2.2-3.9] years; 61 925 male [50.9%]) were included in the study, contributing 21 015 956 person-days of observation. The majority of children (11 294 of 11 705 [96.5%]) received the mRNA-1273 COVID-19 vaccine (Moderna). Vaccine effectiveness against confirmed infection was 45.2% (95% CI, 24.7%-60.2%) in partially vaccinated, infection-naive children and 63.3% (95% CI, 40.6%-77.3%) in fully vaccinated, infection-naive children compared with the unvaccinated group. Among previously infected children, vaccine effectiveness against reinfections in those with at least 1 vaccine dose was estimated at 74.6% (95% CI, 38.7%-89.5%).Conclusions and Relevance Study results suggest that completion of a primary mRNA vaccine series provided protection against SARS-CoV-2 infection in children aged 1 through 4 years. Although incidence of hospitalization and severe illness is low in this age group, there is potential benefit of vaccination in preventing infection and potential sequelae.

The XBB sublineage of the omicron (B.1.1.529) variant of SARS-CoV-2 was first identified in India in August, 2022, and has since spread rapidly around the world.1Ministry of Health SingaporeUpdate on COVID-19 situation and measures to protect healthcare capacity.https://www.moh.gov.sg/news-highlights/details/update-on-covid-19-situation-and-measures-to-protect-healthcare-capacityDate: Oct 15, 2022Date accessed: October 27, 2022Google Scholar, 2Cepeda M Philippines detects first cases of XBB COVID-19 sub-variant, XBC recombinant. The Straits Times.https://www.straitstimes.com/asia/se-asia/philippines-detects-first-cases-of-xbb-covid-19-sub-variant-xbc-recombinantDate: Oct 18, 2022Date accessed: October 27, 2022Google Scholar A recombinant of the BA.2.10.1 and BA.2.75 sublineages,3WHOWeekly epidemiological update on COVID-19—26 October 2022. Edition 115.https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19--26-october-2022Date: Oct 26, 2022Date accessed: October 27, 2022Google Scholar, 4WHOTracking SARS-CoV-2 variants.https://www.who.int/activities/tracking-SARS-CoV-2-variantsDate: Oct 27, 2022Date accessed: October 27, 2022Google Scholar, 5WHOTAG-VE statement on omicron sublineages BQ.1 and XBB.www.who.int/news/item/27-10-2022-tag-ve-statement-on-omicron-sublineages-bq.1-and-xbbDate: Oct 27, 2022Date accessed: October 27, 2022Google Scholar early studies6Cao Y Jian F Wang J et al.Imprinted SARS-CoV-2 humoral immunity induces convergent omicron RBD evolution.Nature. 2023; 614: 521-529PubMed Google Scholar, 7Kurhade C Zou J Xia H et al.Low neutralization of SARS-CoV-2 omicron BA.2.75.2, BQ.1.1, and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster.Nat Med. 2023; 29: 344-347Crossref PubMed Scopus (53) Google Scholar suggested that XBB was one of the most immune-evasive strains tested. However, whether the growth advantage of XBB was sufficient to outcompete other SARS-CoV-2 strains and drive new waves of infection was unclear. The Ministry of Health of Singapore monitors circulating SARS-CoV-2 variants through a national acute respiratory infection surveillance system that includes genomic surveillance. Compared with the omicron subvariants that dominated previous waves of infection in the country (BA.2 in March, 2022, and BA.5 in July, 2022), XBB showed considerably steeper growth—becoming predominant in less than 1 month (compared with 2 months for BA.5), outcompeting the BA.2.75 subvariant that was also increasing in case proportions, and propelling an infection wave in Singapore. We aimed to characterise the traits of the XBB sublineage and compare them with those of other SARS-CoV-2 strains. When the first imported case of XBB infection was detected on Sept 6, 2022, case numbers in Singapore were relatively low and three major omicron subvariants were co-circulating: BA.5 (calculated at 86% of community cases on the basis of S-gene target failure testing and whole-genome sequencing), BA.2.75 (11% of cases, an increase from 0·4% when the first case was detected on July 9, 2022), and BA.2 (3% of cases). By the week commencing Sept 26, 2022, XBB accounted for an estimated 22% of community cases, increasing to 54% the following week and 75% by the week commencing Oct 10, 2022; a sharp increase in case numbers was also reported (figure). We compared the incidence of severe COVID-19 (defined as requiring oxygen supplementation, admission to an intensive care unit, or death within 30 days of a positive test) among all people with first SARS-CoV-2 infections during four waves of infection in Singapore—dominated by delta (B.1.617.2), omicron BA.1 or BA.2, omicron BA.4 or BA.5, and omicron XBB subvariants—between June 1, 2021, and Nov 15, 2022. After adjusting for age, sex, ethnicity, housing type (as a proxy for socioeconomic status), vaccination status, and time since last vaccine dose using a Poisson regression model, we found that individuals infected in the XBB wave were at lower risk of severe COVID-19 than those infected in the delta wave (incidence rate ratio 0·68; 95% CI 0·60–0·76; appendix). These findings, based on comprehensive national data, suggest that infection with XBB results in less severe disease than infection with the delta variant and similar disease severity to infection with omicron BA.4 and BA.5 subvariants. XBB probably also drove the observed increase in SARS-CoV-2 reinfections between Sept 26 and Oct 18, 2022, in which the 7-day moving average proportion of reinfections among confirmed COVID-19 cases increased from 8·2% to 18·8%. Reinfection was defined as a positive test at least 90 days after the last positive test in the same individual. A separate national cohort study8Tan CY Chiew CJ Pang D Protective immunity of SARS-CoV-2 infection and vaccines against medically attended omicron BA.4, BA.5, and XBB reinfection in Singapore: a national cohort study.Lancet Infect Dis. 2023; (published online March 13.)https://doi.org/10.1016/S1473-3099(23)00060-9Summary Full Text Full Text PDF Scopus (2) Google Scholar found that previous infection with pre-omicron variants did not confer protection against XBB reinfection compared with SARS-CoV-2-naive individuals, whereas previous infection with omicron BA.1 or BA.2 subvariants conferred low to moderate protective immunity against XBB reinfection (up to 51%), especially when combined with vaccination for hybrid immunity. This finding could reflect improved immunity against XBB conferred by infection with the better-matched omicron subvariants. The evolution of the omicron variant continues to drive the emergence of new subvariants. In Singapore, the growth advantage of XBB over BA.5 and BA.2.75 was clear, particularly as the proportion of BA.2.75 infections increased from 11% to 35% during the 4 weeks after the country's first imported XBB case. By Nov 1, 2022—2 weeks after the peak of the XBB wave in Singapore—a stable equilibrium had been reached between XBB, BA.5, and BA.2.75 co-circulating in the community. Hybrid immunity from high vaccination rates and previous infection, as well as the availability of antivirals, probably helped to maintain low disease severity; however, as one of the most immune-evasive subvariants to date, XBB still drove a new wave of infections. Many countries have not had XBB waves or do not have the same extent of hybrid immunity in their populations as Singapore, and the prevalent strains of SARS-CoV-2 might vary in different regions of the world as the virus rapidly mutates—for example, European countries are seeing an increase in cases due to the omicron BQ.1 subvariant. This pattern of highly immune-evasive strains resulting in epidemic waves with large numbers of reinfections could be increasingly common in the future. Singapore's experience underscores the importance of continued vigilance to ensure that new subvariants are rapidly characterised, especially now that the lead time for public health responses has been reduced by increased virus transmissibility, the resumption of international travel, and the reopening of societies. We declare no competing interests. Download .pdf (.37 MB) Help with pdf files Supplementary appendix

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 & BULL;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.

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.

BACKGROUND:Emergence of the SARS-CoV-2 omicron (B.1.1.529) variant with high immune evasion has led to the development and roll-out of bivalent mRNA vaccines targeting original and omicron strains. However, real-world observational data on effectiveness of bivalent vaccines are scarce. We aimed to assess the relative effectiveness of a fourth vaccine dose with the BA.1-adapted or BA.4/BA.5-adapted bivalent vaccines against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission among SARS-CoV-2-naive and previously infected individuals in Singapore. METHODS:We conducted a retrospective cohort study among Singapore residents aged 18 years and older who had received three monovalent mRNA vaccine doses and were eligible for a fourth dose. Data were collected from official databases on COVID-19 cases and vaccinations maintained by the Singapore Ministry of Health. We analysed the incidence of medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission between Oct 14, 2022, and Jan 31, 2023, by previous infection status and type of fourth vaccine dose received. Inverse probability-weighted Cox regressions were used to estimate hazard ratios (HRs). FINDINGS:2 749 819 individuals were included in the analysis. For the SARS-CoV-2-naive group, a fourth monovalent vaccine dose did not confer additional protection over three monovalent doses against symptomatic infection (HR 1·09 [95% CI 1·07-1·11]), whereas the bivalent vaccine did provide additional protection (0·18 [0·17-0·19]). Among individuals with previous infection, the HR was 0·87 (95% CI 0·84-0·91) and 0·14 (0·13-0·15) with receipt of the fourth monovalent and bivalent doses, respectively. Against COVID-19-related hospital admission, the bivalent vaccine (HR 0·12 [95% CI 0·08-0·18] in SARS-CoV-2-naive participants and 0·04 [0·01-0·15] in previously infected participants) conferred greater benefit compared with the fourth monovalent dose (0·84 [0·77-0·91] in SARS-CoV-2-naive participants and 0·85 [0·69-1·04] in previously infected participants). INTERPRETATION:A fourth dose with the bivalent vaccine was substantially more effective against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission than four monovalent doses among both SARS-CoV-2-naive and previously infected individuals. Boosters with the bivalent vaccine might be preferred in this omicron-predominant pandemic, regardless of previous infection history. FUNDING:None.

Background: Despite a large proportion of the population vaccinated and naturally infected, Singapore experienced SARS-CoV-2 waves driven by Omicron BA.5 and XBB sublineages. Data on the protective effectiveness of previous SARS-CoV-2 infections and vaccinations against Omicron BA.4/BA.5 and XBB reinfections remain scarce, and can be derived from Singapore's experience as one of the first countries with an XBB-driven wave.Methods: Using official databases from the Singapore Ministry of Health, we conducted a retrospective cohort study among Singapore residents aged ≥18 years to assess hybrid immunity against BA.4/BA.5 reinfections from 1 October 2022 to 1 November 2022 and XBB reinfections from 18 October 2022 to 1 November 2022. Analysis stratified by time from first infection was also conducted to analyse waning immunity. Incidence rate ratios (IRR) were measured by Poisson regressions, with SARS-CoV-2-naive individuals as the reference group. Protective effectiveness (PE) was calculated by taking one minus the risk ratio.Findings: 2,456,791 individuals were included, contributing 53.1 million person-days of observation for the SARS-CoV-2-naive group, and 3.4, 6.6 and 13.7 million person-days to the groups with previous pre-Omicron, BA.1 and BA.2 infections respectively between 1 October 2022 and 1 November 2022. Compared with naïve individuals, first infections with pre-Omicron variants did not confer protection against BA.4/BA.5 (IRR 0.87 [95% CI 0.73–1.05] for pre-Omicron infection with booster) or XBB reinfection (IRR 1.29 [95% CI 1.23–1.35] for pre-Omicron infection with booster). Prior BA.2 infection with boosters provided the greatest protection, but this was lower against reinfection with XBB (PE 51%; 95% CI 49–53%) than BA.4/BA.5 (78%; 95% CI 74–82%). Protection by BA.2 against XBB reinfection also waned faster (74% [95% CI 72–75%) at 3–6 months to 49% [95% CI 47–52%] at 7–8 months) compared with BA.4/BA.5 reinfection (87% [95% CI 82–90%] at 3–6 months to 74% [95% CI 66–80%] at 7–8 months) over time from first infection.Interpretation: Protection from an earlier Omicron infection with vaccination against XBB reinfection was lower and waned faster than that for BA.4/BA.5 reinfection, indicative of XBB's greater immune evasiveness. Populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and natural infection, reflected by high reinfection rates during Singapore's XBB wave.