Dengue versus COVID-19: comparing the incidence of cardiovascular, neuropsychiatric and autoimmune complications.

BACKGROUND: While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was contrasted against that following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a multi-ethnic adult Asian population. METHODS: National testing and healthcare claims that databases in Singapore were utilized to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 July 2021 to 31 October 2022). Risks of new-incident cardiovascular/neuropsychiatric/autoimmune complications 31-300 days of post-dengue infection, contrasted with SARS-CoV-2 infection, were estimated using Cox regression with overlap weights. Risks were reported in terms of adjusted hazard ratio (aHR) and excess burden per 1000 persons. RESULTS: 11 707 dengue-infected individuals and 1 248 326 contemporaneous coronavirus disease 2019 (COVID-19) cases were included; the majority had mild initial infection not requiring hospitalization. Amongst dengue-infected individuals, there was 21% [aHR = 1.21 (1.06-1.38)] increased risk of any sequelae, with 55% [aHR = 1.55 (1.27-1.89)] increased risk of cardiovascular sequelae. Specifically, increased risk of dysrhythmias [aHR = 1.79(1.35-2.37)], ischemic heart disease [aHR = 1.45(1.12-1.89)], other cardiac disorders [aHR = 2.21(1.54-3.16)] and thrombotic disorders [aHR = 2.55(1.50-4.35)] was noted. Elevated risk of individual neuropsychiatric sequelae, including cerebrovascular disorders [aHR = 1.49(1.09-2.13)], cognition/memory disorders [aHR = 2.13(1.55-2.93)], extrapyramidal/movement disorders [aHR = 1.98(1.33-2.94)] and anxiety disorders [aHR = 1.61(1.01-2.56)], was observed in dengue-infected individuals compared to COVID-19 cases. Elevated risks of post-acute sequelae in dengue survivors were observed when contrasted against COVID-19 survivors infected during Delta/Omicron predominance, as well as across vaccination strata. CONCLUSION: Increased risk of post-acute cardiovascular/neuropsychiatric complications was observed in dengue survivors, when contrasted against COVID-19 survivors infected during Delta/Omicron predominance.

A Nationwide Cohort Study of Delta and Omicron SARS-CoV-2 Outcomes in Vaccinated Individuals With Chronic Lung Disease.

BACKGROUND: Individuals with chronic lung disease (CLD) are more susceptible to respiratory viral infections; however, significant heterogeneity exists in the literature on CLD and COVID-19 outcomes. Data are lacking on outcomes with newer variants (eg, Omicron) and in vaccinated and boosted populations. RESEARCH QUESTION: What are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission in a highly vaccinated and boosted population-based cohort? STUDY DESIGN AND METHODS: Outcomes of Delta and Omicron SARS-CoV-2 infection in a highly vaccinated and boosted cohort of adult Singaporeans with CLD (including asthma, COPD, bronchiectasis, and pulmonary fibrosis) were contrasted against matched population control participants. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations, and severe COVID-19 disease, adjusting for sociodemographic factors and comorbidities. RESULTS: Overall, 68,782 individual patients with CLD and 534,364 matched population control participants were included. By the end of the Omicron wave, 92.7% of patients with CLD were boosted. Compared with control participants, patients with CLD showed higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization, and severe COVID-19 during both the Delta wave (infection: adjusted hazards ratio [aHR], 1.22 [95% CI, 1.17-1.28]; hospitalization: aHR, 1.76 [95% CI, 1.61-1.92]; severe COVID-19: aHR, 1.75 [95% CI, 1.50-2.05]) and Omicron wave (infection: aHR, 1.15 [95% CI, 1.14-1.17]; hospitalization: aHR, 1.82 [95% CI, 1.74-1.91]; severe COVID-19: aHR, 2.39 [95% CI, 2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization, and severe COVID-19 was observed among patients with asthma (severe COVID-19: aHR, 1.31 [95% CI, 1.10-1.55]) and COPD (severe COVID-19: aHR, 1.36 [95% CI, 1.12-1.66]) compared with control participants. Severe exacerbation (requiring hospitalization) in the preceding year was associated with higher risk of poorer outcomes (Delta severe COVID-19: aHR, 9.84 [95% CI, 6.33-15.28]; Omicron severe COVID-19: aHR, 19.22 [95% CI, 15.35-24.06]). Risk was attenuated in the boosted group, with numerically lower HRs against hospitalization and severe COVID-19 in the four-dose group compared with the three-dose group. INTERPRETATION: Increased risk of COVID-19-related hospitalization and severe COVID-19 was observed among patients with CLD compared with matched population control participants during Delta and Omicron predominance. Boosting attenuated serious COVID-19 outcomes.

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 before the emergence of the milder Omicron variant. We examined the post-acute risk of new-incident cardiovascular complications after SARS-CoV-2 infection in a multi-ethnic Asian population, during Omicron predominance. METHODS: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals with confirmed SARS-CoV-2 infection during Omicron BA.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 and excess burden. 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 hospitalization. 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 hospitalized (aHR = 2.81 [2.26-3.50]) and severe COVID-19 cases (aHR = 5.52 [3.76-8.10]). DISCUSSION: 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.

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 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.

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.

Effectiveness of Monovalent mRNA Vaccines Against Omicron XBB Infection in Singaporean Children Younger Than 5 Years.

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.

Development and Testing of a Mobile App to Collect Social Determinants of Health Data in Cancer Settings: Interview Study.

BACKGROUND: Social determinants of health (SDOH) such as lack of basic resources, housing, transportation, and social isolation play an important role for patients on the cancer care continuum. Health systems' current technological solutions for identifying and managing patients' SDOH data largely focus on information recorded in the electronic health record by providers, which is often inaccessible to patients to contribute to or modify. OBJECTIVE: We developed and tested a patient-centric SDOH screening tool designed for use on patients' personal mobile phone that preserves patient privacy and confidentiality, collects information about the unmet social needs of patients with cancer, and communicates them to the provider. METHODS: We interviewed 22 patients with cancer, oncologists, and social workers associated with a US-based comprehensive cancer center to better understand how patients' SDOH information is collected and reported. After triangulating data obtained from thematic analysis of interviews, an environmental scan, and a literature search of validated tools to collect SDOH data, we developed an SDOH screening tool mobile app and conducted a pilot study of 16 dyadic pairs of patients and cancer care team members at the same cancer center. We collected patient SDOH data using 36 survey items covering 7 SDOH domains and used validated scales and follow-up interviews to assess the app's usability and acceptability among patients and cancer care team members. RESULTS: Formative interviews with patients and care team members revealed that transportation, financial challenges, food insecurity, and low health literacy were common SDOH challenges and that a mobile app that collected those data, shared those data with care team members, and offered supportive resources could be useful and valuable. In the pilot study, 25% (4/16) of app-using patients reported having at least one of the abovementioned social needs; the most common social need was social isolation (7/16, 44%). Patients rated the mobile app as easy to use, accurately capturing their SDOH, and preserving their privacy but suggested that the app could be more helpful by connecting patients to actual resources. Providers reported high acceptability and usability of the app. CONCLUSIONS: Use of a brief, patient-centric, mobile app-based SDOH screening tool can effectively capture SDOH of patients with cancer for care team members in a way that preserves patient privacy and that is acceptable and usable for patients and care team members. However, only collecting SDOH information is not sufficient; usefulness can be increased by connecting patients directly to resources to address their unmet social needs.

Effectiveness of bivalent mRNA vaccines against medically attended symptomatic SARS-CoV-2 infection and COVID-19-related hospital admission among SARS-CoV-2-naive and previously infected individuals: a retrospective cohort study.

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.

COVID-19 Severity and Waning Immunity After up to 4 mRNA Vaccine Doses in 73 608 Patients With Cancer and 621 475 Matched Controls in Singapore: A Nationwide Cohort Study.

Importance: Despite patients with cancer being at risk of poor outcomes from COVID-19, there are few published studies for vaccine efficacy in this group, with suboptimal immunogenicity and waning vaccine efficacy described in small studies being a concern. Objective: To assess the incidence rate of severe COVID-19 disease outcomes associated with the number of vaccine doses received and the waning of protection over time. Design, Setting, and Participants: A prospective multicenter observational cohort study was carried out over 2 time periods (September 15, 2021, to December 20, 2021 [delta wave], and January 20, 2022, to November 11, 2022 [omicron wave]) predominated by SARS-CoV-2 delta and omicron variants, respectively. Overall, 73 608 patients with cancer (23 217 active treatment, 50 391 cancer survivors) and 621 475 controls matched by age, sex, race and ethnicity, and socioeconomic status were included. Exposure: Vaccine doses received, from zero to 4 doses, and time elapsed since last vaccine dose. Outcomes: Competing-risk regression analyses were employed to account for competing risks of death in patients with cancer. Main outcomes were incidence rate ratios (IRRs) of COVID-19 infection, hospitalization, and severe disease (defined as requirement for supplemental oxygen, intensive care, or death). The IRRs stratified by time from last vaccine dose served as indicators of waning of vaccine effectiveness over time. Results: The mean (SD) age of actively treated patients with cancer, cancer survivors, and controls were 62.7 (14.7), 62.9 (12.6), and 61.8 (14.7) years, respectively. Of 73 608 patients with cancer, 27 170 (36.9%) were men; 60 100 (81.6%) were Chinese, 7432 (10.1%) Malay, 4597 (6.2%) Indian, and 1479 (2.0%) were of other races and ethnicities. The IRRs for the 3-dose and 4-dose vs the 2-dose group (reference) for COVID-19 hospitalization and severe disease were significantly lower during both the delta and omicron waves in cancer and control populations. The IRRs for severe disease in the 3-dose group for active treatment, cancer survivors, and controls were 0.14, 0.13, and 0.07 during the delta wave and 0.29, 0.19, and 0.21 during omicron wave, respectively. The IRRs for severe disease in the 4-dose group during the omicron wave were even lower at 0.13, 0.10 and 0.10, respectively. No waning of vaccine effectiveness against hospitalization and severe disease was seen beyond 5 months after a third dose, nor up to 5 months (the end of this study's follow-up) after a fourth dose. Conclusion: This cohort study provides evidence of the clinical effectiveness of mRNA-based vaccines against COVID-19 in patients with cancer. Longevity of immunity in preventing severe COVID-19 outcomes in actively treated patients with cancer, cancer survivors, and matched controls was observed at least 5 months after the third or fourth dose.

Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission.

OBJECTIVES: Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission. METHODS: Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts. RESULTS: We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant. DISCUSSION: Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.

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.

Erratum to "Impact of delta variant and vaccination on SARS-CoV-2 secondary attack rate among household close contacts" [The Lancet Regional Health - Western Pacific 17 (2021) 100299].

[This corrects the article DOI: 10.1016/j.lanwpc.2021.100299.].

Protective immunity of SARS-CoV-2 infection and vaccines against medically attended symptomatic omicron BA.4, BA.5, and XBB reinfections in Singapore: a national cohort study.

BACKGROUND: Despite a large proportion of the population having been vaccinated and infected, Singapore had SARS-CoV-2 waves driven by the BA.5 and XBB sublineages of the omicron (B.1.1.529) variant. Data on the protective immunity against medically attended, symptomatic reinfections with omicron BA.4, BA.5, and XBB conferred by previous SARS-CoV-2 infections and vaccinations are scarce. We therefore aimed to derive information from Singapore's experience as one of the first countries with an XBB-driven wave. METHODS: For this retrospective national cohort study, we used information from official databases of the Ministry of Health of Singapore to assess hybrid immunity (obtained from previous infection and vaccination) against medically attended, symptomatic BA.4 and BA.5 reinfections from Oct 1, 2022, to Nov 1, 2022, and medically attended, symptomatic XBB reinfections from Oct 18, 2022, to Nov 1, 2022, among Singapore citizens and permanent residents aged at least 18 years. All individuals with acute respiratory symptoms who presented at any health-care facility in Singapore between the stated dates were tested for SARS-CoV-2. Individuals were grouped into SARS-CoV-2-naive, pre-omicron, omicron BA.1, and omicron BA.2 groups according to their previous infection status. Data were also stratified by time from first infection to analyse the waning of immunity. Incidence rate ratios (IRRs) were measured by generalised linear Poisson regressions, with SARS-CoV-2-naive individuals as the reference group, and protective immunity was calculated as one minus the risk ratio multiplied by 100. FINDINGS: 2 456 791 individuals were included in the study, contributing 53·1 million person-days of observation for the SARS-CoV-2-naive group, 3·4 million person-days for the pre-omicron group, 6·6 million person-days for the BA.1 group, and 13·7 million person-days for the BA.2 group between Oct 1, 2022, and Nov 1, 2022. Compared with SARS-CoV-2-naive individuals, first infections with pre-omicron variants did not confer protection against reinfection with BA.4 or BA.5 (IRR 0·87 [95% CI 0·73-1·05] for pre-omicron infection with booster vaccination) or XBB (IRR 1·29 [1·23-1·35] for pre-omicron infection with booster vaccination). Previous BA.2 infection with booster provided the greatest protection against reinfection, but this was lower against reinfection with XBB (protective immunity 51%; 95% CI 49-53) than against reinfection with BA.4 or BA.5 (78%; 74-82). Protection conferred by previous BA.2 infection against XBB reinfection waned faster over time from first infection (from 74% [72-75] at 3-6 months to 49% [47-52] at 7-8 months) than protection against BA.4 or BA.5 reinfection (from 87% [82-90] at 3-6 months to 74% [66-80] at 7-8 months). INTERPRETATION: Protection against XBB reinfection conferred by a previous omicron infection with vaccination was lower and waned faster than protection against BA.4 or BA.5 reinfection, which is indicative of the greater immune evasiveness of the XBB sublineage. Although severe COVID-19 is uncommon, populations remain vulnerable to future reinfection waves from emerging SARS-CoV-2 variants despite high rates of vaccination and infection, as reflected by substantially higher reinfection rates during Singapore's XBB wave than during the previous BA.5-driven wave. Policy makers could consider emerging public health interventions, such as omicron-adapted bivalent vaccines, to maintain population immunity against COVID-19. FUNDING: None.

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.