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

Premikha, M / Chiew, Calvin J / Wei, Wycliffe E / Leo, Yee Sin / Ong, Benjamin / Lye, David Chien / Lee, Vernon J / Tan, Kelvin Bryan

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 75, Issue 8, Page(s) 1442–1445

Abstract: Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29-2.46) and 1.62 (95% CI, 1.43-1.85) times more likely to be infected with coronavirus disease 19, respectively, ... ...

Abstract	Compared with individuals vaccinated with Pfizer-BioNTech/Comirnaty, recipients of Sinovac-CoronaVac and Sinopharm were 2.37 (95% CI, 2.29-2.46) and 1.62 (95% CI, 1.43-1.85) times more likely to be infected with coronavirus disease 19, respectively, while individuals vaccinated with Moderna were 0.42 (95% CI, 0.25-0.70) times less likely to develop severe disease.
MeSH term(s)	COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; RNA, Messenger ; Singapore/epidemiology ; Vaccines, Inactivated
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Inactivated
Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac288
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Article ; Online: Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020.

Wei, Wycliffe E / Li, Zongbin / Chiew, Calvin J / Yong, Sarah E / Toh, Matthias P / Lee, Vernon J

MMWR. Morbidity and mortality weekly report

2020 Volume 69, Issue 14, Page(s) 411–415

Abstract: Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 ... ...

Abstract	Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.
MeSH term(s)	Adult ; Asymptomatic Diseases ; Betacoronavirus ; Cluster Analysis ; Contact Tracing ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Singapore/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	412775-4
ISSN	1545-861X ; 0149-2195
ISSN (online)	1545-861X
ISSN	0149-2195
DOI	10.15585/mmwr.mm6914e1
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Article ; Online: 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.

Chiew, Calvin J / Premikha, M / Chong, Chia Yin / Wei, Wycliffe E / Ong, Benjamin / Lye, David Chien / Heng, Derrick / Lee, Vernon J / Tan, Kelvin Bryan

The Lancet. Infectious diseases

2022 Volume 23, Issue 2, Page(s) 177–182

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Humans ; Adolescent ; Singapore/epidemiology ; BNT162 Vaccine ; COVID-19/epidemiology ; COVID-19/prevention & control ; Cohort Studies ; SARS-CoV-2 ; Hospitalization ; Vaccination
Chemical Substances	BNT162 Vaccine
Language	English
Publishing date	2022-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00573-4
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Article ; Online: Effect of Housing Type and Neighborhood Socioeconomic Indicators on Survival After Low Falls in Older Adults.

Wei, Wycliffe E / Wong, Chek Hooi / Matchar, David B / Earnest, Arul / Wah, Win / Ong, Marcus Eng Hock / Wong, Ting Hway

Journal of the American Medical Directors Association

2019 Volume 20, Issue 5, Page(s) 646–649

MeSH term(s)	Accidental Falls/mortality ; Aged ; Female ; Humans ; Male ; Poverty/statistics & numerical data ; Registries/statistics & numerical data ; Residence Characteristics/statistics & numerical data ; Singapore ; Social Support ; Socioeconomic Factors ; Wounds and Injuries/mortality
Language	English
Publishing date	2019-02-20
Publishing country	United States
Document type	Letter
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2018.12.016
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Article: Presymptomatic Transmission of SARS-CoV-2 - Singapore, January 23-March 16, 2020

Wei, Wycliffe E / Li, Zongbin / Chiew, Calvin J / Yong, Sarah E / Toh, Matthias P / Lee, Vernon J

MMWR Morb Mortal Wkly Rep

Abstract	Presymptomatic transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), might pose challenges for disease control. The first case of COVID-19 in Singapore was detected on January 23, 2020, and by March 16, a total of 243 cases had been confirmed, including 157 locally acquired cases. Clinical and epidemiologic findings of all COVID-19 cases in Singapore through March 16 were reviewed to determine whether presymptomatic transmission might have occurred. Presymptomatic transmission was defined as the transmission of SARS-CoV-2 from an infected person (source patient) to a secondary patient before the source patient developed symptoms, as ascertained by exposure and symptom onset dates, with no evidence that the secondary patient had been exposed to anyone else with COVID-19. Seven COVID-19 epidemiologic clusters in which presymptomatic transmission likely occurred were identified, and 10 such cases within these clusters accounted for 6.4% of the 157 locally acquired cases. In the four clusters for which the date of exposure could be determined, presymptomatic transmission occurred 1-3 days before symptom onset in the presymptomatic source patient. To account for the possibility of presymptomatic transmission, officials developing contact tracing protocols should strongly consider including a period before symptom onset. Evidence of presymptomatic transmission of SARS-CoV-2 underscores the critical role social distancing, including avoidance of congregate settings, plays in controlling the COVID-19 pandemic.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #45948
Database	COVID19

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Article ; Online: Post-stroke patients with moderate function have the greatest risk of falls: a National Cohort Study.

Wei, Wycliffe E / De Silva, Deirdre A / Chang, Hui Meng / Yao, Jiali / Matchar, David B / Young, Sherry H Y / See, Siew Ju / Lim, Gek Hsiang / Wong, Ting Hway / Venketasubramanian, Narayanaswamy

BMC geriatrics

2019 Volume 19, Issue 1, Page(s) 373

Abstract: Background: Stroke patients have increased risks of falls. We examined national registry data to evaluate the association between post-stroke functional level and the risk of low falls among post-stroke patients.: Methods: This retrospective cohort ... ...

Abstract	Background: Stroke patients have increased risks of falls. We examined national registry data to evaluate the association between post-stroke functional level and the risk of low falls among post-stroke patients. Methods: This retrospective cohort study analyzed data from national registries to examine the risk factors for post-stroke falls. Data for patients who suffered ischemic strokes and survived the index hospital admission was obtained from the Singapore National Stroke Registry and matched to the National Trauma Registry, from 2011 to 2015. The primary outcome measure was a low fall (fall height ≤ 0.5 m). Competing risk analysis was performed to examine the association between functional level (by modified Rankin score [mRS] at discharge) and the risk of subsequent low falls. Results: In all, 2255 patients who suffered ischemic strokes had recorded mRS. The mean age was 66.6 years and 58.5% were men. By the end of 2015, 54 (2.39%) had a low fall while 93 (4.12%) died. After adjusting for potential confounders, mRS was associated with fall risk with an inverted U-shaped relationship. Compared to patients with a score of zero, the sub-distribution hazard ratio (SHR) increased to a maximum of 3.42 (95%CI:1.21-9.65, p = 0.020) for patients with a score of 2. The SHR then declined to 2.45 (95%CI:0.85-7.12, p = 0.098), 2.86 (95%CI:0.95-8.61, p = 0.062) and 1.93 (95%CI:0.44-8.52, p = 0.38) for patients with scores of 3, 4 and 5 respectively. Conclusions: An inverted U-shaped relationship between functional status and fall risk was observed. This is consistent with the complex interplay between decreasing mobility (hence decreased opportunity to fall) and increasing susceptibility to falls. Fall prevention intervention could be targeted accordingly. (263 words).
MeSH term(s)	Accidental Falls/prevention & control ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Hospitalization/trends ; Humans ; Male ; Middle Aged ; Patient Discharge/trends ; Recovery of Function/physiology ; Registries ; Retrospective Studies ; Risk Factors ; Singapore/epidemiology ; Stroke/epidemiology ; Stroke/physiopathology ; Stroke/psychology
Language	English
Publishing date	2019-12-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-019-1377-7
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Article ; Online: Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes

Barnaby E Young / Wycliffe E Wei / Siew-Wai Fong / Tze-Minn Mak / Danielle E Anderson / Yi-Hao Chan / Rachael Pung / Cheryl SY Heng / Li Wei Ang / Adrian Kang Eng Zheng / Bernett Lee / Shirin Kalimuddin / Surinder Pada / Paul A Tambyah / Purnima Parthasarathy / Seow Yen Tan / Louisa Sun / Gavin JD Smith / Raymond Tzer Pin Lin /

Yee-Sin Leo / Laurent Renia / Lin-Fa Wang / Lisa FP Ng / Sebastian Maurer-Stroh / David Chien Lye / Vernon J Lee

EBioMedicine, Vol 66, Iss , Pp 103319- (2021)

An observational study

2021

Abstract: Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. ...

Abstract	Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades ‘O’ were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002–0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064–0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35–2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher ...
Keywords	COVID-19 ; SARS-CoV-2 ; Clade ; D614G ; Severity ; Transmission ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610 ; 616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study.

Young, Barnaby E / Wei, Wycliffe E / Fong, Siew-Wai / Mak, Tze-Minn / Anderson, Danielle E / Chan, Yi-Hao / Pung, Rachael / Heng, Cheryl Sy / Ang, Li Wei / Zheng, Adrian Kang Eng / Lee, Bernett / Kalimuddin, Shirin / Pada, Surinder / Tambyah, Paul A / Parthasarathy, Purnima / Tan, Seow Yen / Sun, Louisa / Smith, Gavin Jd / Lin, Raymond Tzer Pin /

Leo, Yee-Sin / Renia, Laurent / Wang, Lin-Fa / Ng, Lisa Fp / Maurer-Stroh, Sebastian / Lye, David Chien / Lee, Vernon J

EBioMedicine

2021 Volume 66, Page(s) 103319

Abstract	Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades 'O' were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.
MeSH term(s)	Adult ; Age Factors ; Aged ; COVID-19/epidemiology ; COVID-19/etiology ; COVID-19/immunology ; COVID-19/transmission ; Comorbidity ; Female ; Humans ; Hypoxia/therapy ; Hypoxia/virology ; Male ; Middle Aged ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Singapore/epidemiology ; Viral Load
Language	English
Publishing date	2021-04-08
Publishing country	Netherlands
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2021.103319
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Article ; Online: Connecting clusters of COVID-19

The Lancet Infectious Diseases

an epidemiological and serological investigation

2020 Volume 20, Issue 7, Page(s) 809–815

Keywords	Infectious Diseases ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/s1473-3099(20)30273-5
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Article ; Online: Connecting clusters of COVID-19: an epidemiological and serological investigation.

The Lancet. Infectious diseases

2020 Volume 20, Issue 7, Page(s) 809–815

Abstract: Background: Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of ...

Abstract	Background: Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods: In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings: Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation: Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding: National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).
MeSH term(s)	Betacoronavirus ; COVID-19 ; Cluster Analysis ; Contact Tracing ; Coronavirus Infections/blood ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Population Surveillance ; SARS-CoV-2 ; Serologic Tests ; Singapore/epidemiology
Chemical Substances	Immunoglobulin G
Keywords	covid19
Language	English
Publishing date	2020-04-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(20)30273-5
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