BNT162b2 vaccine protection against omicron and effect of previous infection variant and vaccination sequence among children and adolescents in Singapore: a population-based cohort study.

BACKGROUND: Information on variant-specific vaccine protection and the effect of previous infection variant is scarce in children. We aimed to ascertain the level of protection conferred by BNT162b2 COVID-19 vaccination against omicron variant infection (BA.4 or BA.5, and XBB) in a previously infected national paediatric cohort. We also explored the association between sequence of previous infection (variant) and vaccination on protection. METHODS: We did a retrospective, population-based cohort study using the national databases of all confirmed SARS-CoV-2 infections, vaccines administered, and demographic records maintained by the Ministry of Health, Singapore. The study cohort consisted of children aged 5-11 years and adolescents aged 12-17 years who had a previous SARS-CoV-2 infection from Jan 1, 2020, to Dec 15, 2022. People who were infected during the pre-delta period or were immunocompromised (received three vaccination doses [children 5-11 years old] and four vaccinations doses [adolescents 12-17 years old]) were excluded. Those who had multiple episodes of infection before the study start date, were not vaccinated before infection but completed three doses, received bivalent mRNA vaccine, or received non-mRNA vaccine doses were also excluded. All SARS-CoV-2 infections confirmed by reverse transcriptase polymerase chain reaction or rapid antigen testing were grouped into delta, BA.1, BA.2, BA.4 or BA.5, or XBB variants using a combination of whole-genome sequencing, S-gene target failure results, and imputation. For BA.4 or BA.5, the study outcome period was June 1-Sept 30, 2022, and for XBB variants the outcome period was Oct 18-Dec 15, 2022. Incidence rate ratios between vaccinated and unvaccinated were derived using adjusted Poisson regressions and vaccine effectiveness was estimated as (1-risk ratio) × 100%. FINDINGS: 135 197 people aged 5-17 years (79 332 children and 55 865 adolescents) were included in the cohort for the vaccine effectiveness analysis against omicron BA.4 or BA.5, and 164 704 people aged 5-17 years (97 235 children and 67 469 adolescents) were included for the analysis against omicron XBB. Approximately 47% of participants were female and 53% were male. Among those previously infected, vaccine effectiveness against BA.4 or BA.5 infection in fully vaccinated children (two doses) was 74·0% (95% CI 67·7-79·1) and in adolescents (three doses) was 85·7% (80·2-89·6). Against XBB, protection conferred with full vaccination was lower at 62·8% (95% CI 42·3-76·0) in children and 47·9% (20·2-66·1) in adolescents. In children, receipt of two-dose vaccination before first SARS-CoV-2 infection provided them with the highest protection against subsequent BA.4 or BA.5 infection at 85·3% (95% CI 80·2-89·1); however, this was not shown to be the case for adolescents. First infection variant had an effect on vaccine effectiveness against omicron BA.4 or BA.5 reinfection in the following descending order: BA.2 conferred the highest protection (92·3% [95% CI 88·9-94·7] in children and 96·4% [93·5-98·0] in adolescents) followed by BA.1 (81·9% [75·9-86·4] in children and 95·0% [91·6-97·0] in adolescents), and delta which conferred the lowest protection (51·9% [5·3-75·6] in children and 77·5% [63·9-86·0] in adolescents). INTERPRETATION: In previously infected children and adolescents, BNT162b2 vaccination provided additional protection against omicron BA.4 or BA.5 and XBB variants compared with those who remained unvaccinated. Hybrid immunity against XBB was lower than against BA.4 or BA.5, especially in adolescents. Early vaccination of previously uninfected children before their first SARS-CoV-2 exposure could potentially strengthen population immunity resilience against future variants. FUNDING: None.

SARS-CoV-2 antigen rapid tests and universal screening for COVID-19 Omicron variant among hospitalized children.

BACKGROUND: Clinical utility of universal antigen rapid test (ART) in the pediatric setting is unknown. We aimed to assess the performance and utility of universal ART in hospitalized children (≥5-year-old) to prevent nosocomial COVID-19 transmission. METHODS: Cross-sectional study involving all hospitalized pediatric patients aged ≥5-year-old from 2 periods during Omicron wave. Clinical data, ART and polymerase chain reaction test results were collected. RESULTS: A total of 444 patients were included from the 2 study periods, and 416 patients (93.7%) had concordant results between ART and polymerase chain reaction. The overall sensitivity and specificity of ART were 83.3% (95% CI: 75.2-89.3) and 97.5% (95% CI: 95.0-98.8), respectively. Negative predictive values of ART between the Omicron emergence and Omicron peak periods for a probable case group were 71.4% and 66.7%, respectively, and for a suspect case group 91.4% and 75.0%, respectively. Negative predictive values for an unlikely case group was >95% in both periods. Positive predictive value of ART was >85% for probable and suspect case groups in both periods. Seventy-five percent of patients (n = 15) who were incorrectly classified as SARS-CoV-2 negative by ART had potentially viable virus. No large nosocomial transmission clusters were detected. CONCLUSIONS: Universal ART screening may limit nosocomial outbreaks in hospitalized children. The performance can be optimized by considering clinical symptoms, exposure and periods within COVID waves.

Combating a resurgence of poliomyelitis through public health surveillance and vaccination.

Poliomyelitis, or polio, is a highly infectious disease and can result in permanent flaccid paralysis of the limbs. Singapore was certified polio-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region. The last imported case of polio in Singapore was in 2006. Fortunately, polio is vaccine-preventable-the world saw the global eradication of wild poliovirus types 2 and 3 achieved in 2015 and 2019, respectively. However, in late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus (VDPV) was detected in countries like Israel and the US (specifically, New York); VDPV was also detected during routine sewage water surveillance with no paralysis cases in London, UK. Without global eradication, there is a risk of re-infection from importation and spread of wild poliovirus or VDPV, or new emergence and circulation of VDPV. During the COVID-19 pandemic, worldwide routine childhood vaccination coverage fell by 5% to 81% in 2020-2021. Fortunately, Singapore has maintained a constantly high vaccination coverage of 96% among 1-year-old children as recorded in 2021. All countries must ensure high poliovirus vaccination coverage in their population to eradicate poliovirus globally, and appropriate interventions must be taken to rectify this if the coverage falters. In 2020, WHO approved the emergency use listing of a novel oral polio vaccine type 2 for countries experiencing circulating VDPV type 2 outbreaks. Environmental and wastewater surveillance should be implemented to allow early detection of "silent" poliovirus transmission in the population, instead of relying on clinical surveillance of acute flaccid paralysis based on case definition alone.

Multisystem inflammatory syndrome in children in Singapore.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women's and Children's Hospital (KKH) from October 2021 to December 2021. METHOD: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. RESULTS: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00-9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. CONCLUSION: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes.

Safety of Pfizer-BioNtech COVID-19 Vaccine in Healthcare Workers, Singapore

Background On 14 December 2020, the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine was granted emergency use authorization in Singapore. Healthcare workers (HCW) were prioritized to receive the vaccine. We aim to investigate the side effects and risk factors for allergic reactions in our institution. Methods All HCW vaccinations were recorded in an electronic centralized database. All reactions occurring within a 30-minute observation period post vaccination were recorded. Staff were required to report any vaccine-related medical consult including hospitalization occurring within 14 days after vaccination. Moderate/severe reactions were assessed by a medical team and determined if the reactions were probable allergic reactions with consultation with an Allergist. We extracted data from 8 Jan 2021 to 30 April 2021. Results 5030 and 159 HCW completed 2 doses and 1 dose of the vaccine respectively. There were 1056 HCWs (20.3%) with self-reported pre-existing allergy. There were 114 (1.1%) reactions occurring without the 30-minute observation period, and 64 (56.1%) were related to first dose of vaccine. The most common side effect experienced was aches or pain on any part of the body (n=46, 40.4%) followed by fatigue and/or giddiness (n=45, 39.5%), palpitations and/or shortness of breath (n=22, 19.3%), systemic rash and/or angioedema (n=12, 10.5%) and nausea and/or vomiting (n=12, 10.5%). A total of 23 HCWs complained of systemic rash and/or angioedema that occurred anytime post vaccination. Fifteen HCWs (0.29% of the cohort) were considered to have probable allergic reaction to the vaccine. None of the reactions were classified as anaphylaxis or severe reactions, but 4 HCWs required short hospitalization stay for observation. HCWs with pre-existing allergy had 2.6 times the risk of having probable vaccine-related allergic reaction than HCWs without pre-existing allergy (RR 2.6, 95% CI 0.9 to 7.3, p=0.068) but this was not statistically significant. Conclusion No anaphylaxis or severe reactions were observed in our institution. Acute side effects in our cohort were in line with published trial reports. We noted a raised relative risk of 2.6 of pre-existing allergy with probable vaccine-related allergic reaction but this was not statistically significant. Disclosures All Authors: No reported disclosures

Pediatric Kawasaki Disease Trends Prior to and During COVID-19 Outbreak in Singapore.

Kawasaki disease (KD, typical/atypical/partial) admissions (n = 644) were surveyed from 2017 to 2020 and compared to urinary tract infection (UTI) admissions and COVID-19 in 2020. KD admissions decreased by 27% and median KD age decreased in 2020, whereas UTI admissions remained steady. KD admissions showed a seasonality with a peak in April and nadir in February-March. All KD/KD-related pediatric intensive care unit cases tested negative for COVID-19, and no multisystem inflammatory syndrome in children was found.

A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19.

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (Teff) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (Treg) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ+ memory CD4+ T cells and virus-specific follicular helper T (TFH) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.

Clinical Utility of Buccal Swabs for Severe Acute Respiratory Syndrome Coronavirus 2 Detection in Coronavirus Disease 2019-Infected Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)-infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children.

Comparative Analysis of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children

Introduction: In this study, a comparison of clinical, epidemiological and laboratory parameters between symptomatic and asymptomatic children with SARS-CoV-2 infection was performed. Materials and Methods: Data from all children with laboratory confirmed SARS-CoV-2 infection admitted to KK Women's and Children's Hospital (KKH), Singapore, from January to May 2020 were analysed. Results: Of the 39 COVID-19 children included, 38.5% were asymptomatic. Household transmission accounted for 95% of cases. The presenting symptoms of symptomatic children were low-grade fever (54.2%), rhinorrhoea (45.8%), sore throat (25%), diarrhoea (12.5%) and acute olfactory dysfunction (5.4%). Children of Chinese ethnicity (37.5% vs 6.7%), complete blood count (45.8% vs 6.7%) and liver enzyme abnormalities (25% vs 7.7%) were more common in symptomatic versus asymptomatic children. All children had a mild disease course and none required oxygen supplementation or intensive care. Conclusions: The high proportion of asymptomatic infected children coupled with household transmission as the main source of paediatric COVID-19 infection underscores the importance of early screening and isolation of children upon detection of an index case of COVID-19 in a household. Symptomatic children were more likely to have abnormal laboratory parameters but they did not have a poorer outcome compared to asymptomatic cases.

A Well Infant With Coronavirus Disease 2019 With High Viral Load.

A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs up to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19, as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from Adults to Children.

Knowledge of transmission dynamics of severe acute respiratory syndrome coronavirus 2 from adults to children in household settings is limited. We found an attack rate among 213 children in 137 households to be 6.1% in households with confirmed adult 2019 novel coronavirus disease index case(s). Transmission from adult to child occurred in only 5.2% of households. Young children <5 years old were at lowest risk of infection (1.3%). Children were most likely to be infected if the household index case was the mother.

Novel Coronavirus 2019 Transmission Risk in Educational Settings.

Transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in schools is unknown. Our investigations, especially in preschools, could not detect SARS-CoV-2 transmission despite screening of symptomatic and asymptomatic children. The data suggest that children are not the primary drivers of SARS-CoV-2 transmission in schools and could help inform exit strategies for lifting of lockdowns.