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1. Pathogen genomic surveillance status among lower resource settings in Asia

Author

Getchell, Marya, Wulandari, Suci, de Alwis, Ruklanthi, Agoramurthy, Shreya, Khoo, Yoong Khean, Mak, Tze-Minn, Moe, La, Stona, Anne-Claire, Pang, Junxiong, Momin, Muhd Haziq Fikry Haji Abdul, Amir, Afreenish, Andalucia, Lucia Rizka, Azzam, Ghows, Chin, Savuth, Chookajorn, Thanat, Arunkumar, Govindakarnavar, Hung, Do Thai, Ikram, Aamer, Jha, Runa, Karlsson, Erik A., Le Thi, Mai Quynh, Mahasirimongkol, Surakameth, Malavige, Gathsaurie Neelika, Manning, Jessica E., Munira, Syarifah Liza, Trung, Nguyen Vu, Nisar, Imran, Qadri, Firdausi, Qamar, Farah Naz, Robinson, Matthew T., Saloma, Cynthia P., Setk, Swe, Shirin, Tahmina, Tan, Le Van, Dizon, Timothy John R., Thayan, Ravindran, Thu, Hlaing Myat, Tissera, Hasitha, Xangsayarath, Phonepadith, Zaini, Zainun, Lim, John C. W., Maurer-Stroh, Sebastian, Smith, Gavin J. D., Wang, Lin-Fa, and Pronyk, Paul

Published
2024
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2. Advancing pathogen genomics in resource-limited settings

Author

Pronyk, Paul Michael, de Alwis, Ruklanthi, Rockett, Rebecca, Basile, Kerri, Boucher, Yann Felix, Pang, Vincent, Sessions, October, Getchell, Marya, Golubchik, Tanya, Lam, Connie, Lin, Raymond, Mak, Tze-Minn, Marais, Ben, Twee-Hee Ong, Rick, Clapham, Hannah Eleanor, Wang, Linfa, Cahyorini, Yorin, Polotan, Francisco Gerardo M., Rukminiati, Yuni, Sim, Eby, Suster, Carl, Smith, Gavin J.D., and Sintchenko, Vitali

Published
2023
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3. Impact of Delta Variant and Vaccination on SARS-CoV-2 Secondary Attack Rate Among Household Close Contacts

Author

Ng, Oon Tek, Koh, Vanessa, Chiew, Calvin J, Marimuthu, Kalisvar, Thevasagayam, Natascha May, Mak, Tze Minn, Chua, Joon Kiat, Ong, Shannen Si Hui, Lim, Yong Kai, Ferdous, Zannatul, Johari, Alifa Khairunnisa bte, Chen, Mark I-Cheng, Maurer-Stroh, Sebastian, Cui, Lin, Lin, Raymond Tzer Pin, Tan, Kelvin Bryan, Cook, Alex R, Leo, Prof. Yee-Sin, and Lee, Prof. Vernon JM

Published
2021
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4. Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study

Author

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, and Lee, Vernon J

Published
2021
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5. Imported Monkeypox, Singapore

Author

Yong, Sarah Ee Fang, Ng, Oon Tek, Ho, Zheng Jie Marc, Mak, Tze Minn, Marimuthu, Kalisvar, Vasoo, Shawn, Yeo, Tsin Wen, Ng, Yi Kai, Cui, Lin, Ferdous, Zannatul, Chia, Po Ying, Aw, Bryan Jun Wei, Manauis, Charmaine Malenab, Low, Constance Khia Ki, Chan, Guanhao, Peh, Xinyi, Lim, Poh Lian, Chow, Li Ping Angela, Chan, Monica, Lee, Vernon Jian Ming, Lin, Raymond Tzer Pin, Heng, Mok Kwee Derrick, and Leo, Yee Sin

Subjects
Human monkeypox, Vaccination, Quarantine, Zoonoses, Travelers, Disease susceptibility, Smallpox vaccine -- International trade, Health
Abstract

Monkeypox is a zoonosis endemic to West and Central Africa; human cases were first reported in 1970 (1). An outbreak ongoing in Nigeria since 2017 is the largest documented (2). [...]

Published
2020
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6. Burden and Cost of Hospitalization for Respiratory Syncytial Virus in Young Children, Singapore

Author

Tam, Clarence C., Yeo, Kee Thai, Tee, Nancy, Lin, Raymond, Mak, Tze Minn, Thoon, Koh Cheng, Jit, Mark, and Yung, Chee Fu

Subjects
Monte Carlo methods -- Health aspects -- Analysis -- Economic aspects, Health care costs -- Analysis -- Health aspects -- Economic aspects, Diseases -- Health aspects -- Analysis -- Economic aspects, Pediatrics -- Analysis -- Health aspects -- Economic aspects, Health
Abstract

Respiratory syncytial virus (RSV) is the commonest cause of acute lower respiratory tract infection in children Several RSV vaccines are in development. Potential immunization strategies include vaccination of children, pregnant [...]

Published
2020
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7. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

Author

Chia, Po Ying, Ong, Sean Wei Xiang, Chiew, Calvin J., Ang, Li Wei, Chavatte, Jean-Marc, Mak, Tze-Minn, Cui, Lin, Kalimuddin, Shirin, Chia, Wan Ni, Tan, Chee Wah, Chai, Louis Yi Ann, Tan, Seow Yen, Zheng, Shuwei, Lin, Raymond Tzer Pin, Wang, Linfa, Leo, Yee-Sin, Lee, Vernon J., Lye, David Chien, and Young, Barnaby Edward

Published
2022
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10. 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]

Author

Ng, Oon Tek, primary, Koh, Vanessa, additional, Chiew, Calvin J., additional, Marimuthu, Kalisvar, additional, Thevasagayam, Natascha May, additional, Mak, Tze Minn, additional, Chua, Joon Kiat, additional, Hui Ong, Shannen Si, additional, Lim, Yong Kai, additional, Ferdous, Zannatul, additional, Khairunnisa bte Johari, Alifa, additional, I-Cheng Chen, Mark, additional, Maurer-Stroh, Sebastian, additional, Cui, Lin, additional, Pin Lin, Raymond Tzer, additional, Tan, Kelvin Bryan, additional, Cook, Alex R., additional, Leo, Prof. Yee-Sin, additional, and Lee, Prof. Vernon J.M., additional

Published
2023
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14. Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Pediatric Age on Delta Variant Household Transmission

Author

Ng, Oon Tek, primary, Koh, Vanessa, additional, Chiew, Calvin J, additional, Marimuthu, Kalisvar, additional, Thevasagayam, Natascha May, additional, Mak, Tze Minn, additional, Chua, Joon Kiat, additional, Ong, Shannen Si Hui, additional, Lim, Yong Kai, additional, Ferdous, Zannatul, additional, Johari, Alifa Khairunnisa bte, additional, Cui, Lin, additional, Lin, Raymond Tzer Pin, additional, Tan, Kelvin Bryan, additional, Cook, Alex R, additional, Leo, Yee Sin, additional, and Lee, Vernon J M, additional

Published
2022
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15. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Author

Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Lye, David Chien, Lim, Poh Lian, Peng Ang, Brenda Sze, Lee, Cheng Chuan, U Lee, Lawrence Soon, Ling, Li Min, Ng, Oon Tek, Chan, Monica, Marimuthu, Kalisvar, Vasoo, Shawn, Wong, Chen Seong, Lee, Tau Hong, Sadarangani, Sapna, Lin, Ray Junhao, Sadasiv, Mucheli Sharavan, Ling Ng, Deborah Hee, Choy, Chiaw Yee, En Tan, Glorijoy Shi, Tan, Yu Kit, Sutjipto, Stephanie, Lee, Pei Hua, Tay, Jun Yang, Yeo, Tsin Wen, Khoo, Bo Yan, Tay, Woo Chiao, Ng, Gabrielle, Mah, Yun Yuan, Tan, Wilnard, De, Partha Pratim, Pooja, Rao, Chia, Jonathan W Z, Constance Chen, Yuan Yi, Mendis, Shehara, Toh, Boon Kiat, Choon Fong, Raymond Kok, Lin Oh, Helen May, Fong Chien, Jaime Mei, Shafi, Humaira, Cheong, Hau Yiang, Tan, Thean Yen, Tan, Thuan Tong, Tan, Ban Hock, Wijaya, Limin, Venkatachalam, Indumathi, Chua, Ying Ying, Zhi Cherng, Benjamin Pei, Zi Chan, Yvonne Fu, Wong, Hei Man, Thien, Siew Yee, Meng Goh, Kenneth Choon, Ling Tan, Shireen Yan, Ean Oon, Lynette Lin, Chan, Kian Sing, Lin, Li, Gin Chan, Douglas Su, Ooi, Say Tat, Narayana, Deepak Rama, Somani, Jyoti, Ling Oon, Jolene Ee, Yan, Gabriel Zherong, Allen, David Michael, Jureen, Roland, Yan, Benedict, Foo, Randy, Kang, Adrian, Sivalingam, Velraj, How, Wilson, Fernandez, Norman Leo, Yeo, Nicholas Kim-Wah, Chee, Rhonda Sin-Ling, Amrun, Siti Naqiah, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Saw Swee Hock School of Public Health, NUS

Subjects
0301 basic medicine, Microbiology (medical), biology, Viral culture, business.industry, 030106 microbiology, COVID-19, medicine.disease, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Infectious Diseases, Immune system, Immunoglobulin M, Viral pneumonia, Immunology, Severity of illness, medicine, biology.protein, Cytokines, Medicine [Science], 030212 general & internal medicine, Seroconversion, Antibody, business
Abstract

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.

Published
2020

16. Epidemiological, Clinical, and Phylogenetic Characteristics of the First SARS-CoV-2 Transmission in a Nursing Home of Singapore: A Prospective Observational Investigation

Author

Pang, Junxiong, primary, Tan, Huei Nuo, additional, Mak, Tze Minn, additional, Octavia, Sophie, additional, Maurer-Stroh, Sebastian, additional, Sirota, Fernanda L., additional, Chan, Mark Peng Chew, additional, Leong, Ian Yi Onn, additional, Koh, Valerie T. J., additional, Ooi, Peng Lim, additional, Vasoo, Shawn, additional, Fisher, Dale, additional, Cui, Lin, additional, Rafman, Heidi, additional, Cutter, Jeffery, additional, and Lee, Vernon J., additional

Published
2022
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17. Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta)

Author

Ong, Sean Wei Xiang, Chiew, Calvin J, Ang, Li Wei, Mak, Tze-Minn, Cui, Lin, Toh, Matthias Paul H S, Lim, Yi Ding, Lee, Pei Hua, Lee, Tau Hong, Chia, Po Ying, Maurer-Stroh, Sebastian, Lin, Raymond T P, Leo, Yee-Sin, Lee, Vernon J, Lye, David Chien, and Young, Barnaby Edward

Subjects
B.1.617.2, Cohort Studies, AcademicSubjects/MED00290, SARS-CoV-2, Major Article, COVID-19, severity, Humans, variants of concern, Retrospective Studies
Abstract

Background he impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. Methods National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all patients with VOC infection admitted to our center between 20-December-2020 and 12-May-2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January-April 2020. Results 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4.90, [95% CI 1.43-30.78]). 157 of these patients were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1.88 [95% CI 0.95-3.76]) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower PCR Ct values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide an impetus for the rapid implementation of vaccination programs.

Published
2021

19. Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta)

Author

Ong, Sean Wei Xiang, primary, Chiew, Calvin J, additional, Ang, Li Wei, additional, Mak, Tze Minn, additional, Cui, Lin, additional, Toh, Matthias Paul H S, additional, Lim, Yi Ding, additional, Lee, Pei Hua, additional, Lee, Tau Hong, additional, Chia, Po Ying, additional, Maurer-Stroh, Sebastian, additional, Lin, Raymond T P, additional, Leo, Yee Sin, additional, Lee, Vernon J, additional, Lye, David Chien, additional, and Young, Barnaby Edward, additional

Published
2021
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20. Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Respiratory Aerosols Emitted by Patients With Coronavirus Disease 2019 (COVID-19) While Breathing, Talking, and Singing

Author

Coleman, Kristen K, primary, Tay, Douglas Jie Wen, additional, Tan, Kai Sen, additional, Ong, Sean Wei Xiang, additional, Than, The Son, additional, Koh, Ming Hui, additional, Chin, Yi Qing, additional, Nasir, Haziq, additional, Mak, Tze Minn, additional, Chu, Justin Jang Hann, additional, Milton, Donald K, additional, Chow, Vincent T K, additional, Tambyah, Paul Anantharajah, additional, Chen, Mark, additional, and Tham, Kwok Wai, additional

Published
2021
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22. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study

Author

Chia, Po Ying, primary, Xiang Ong, Sean Wei, additional, Chiew, Calvin J, additional, Ang, Li Wei, additional, Chavatte, Jean-Marc, additional, Mak, Tze-Minn, additional, Cui, Lin, additional, Kalimuddin, Shirin, additional, Chia, Wan Ni, additional, Tan, Chee Wah, additional, Ann Chai, Louis Yi, additional, Tan, Seow Yen, additional, Zheng, Shuwei, additional, Pin Lin, Raymond Tzer, additional, Wang, Linfa, additional, Leo, Yee-Sin, additional, Lee, Vernon J, additional, Lye, David Chien, additional, and Young, Barnaby Edward, additional

Published
2021
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23. Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing

Author

Coleman, Kristen K., primary, Wen Tay, Douglas Jie, additional, Tan, Kai Sen, additional, Xiang Ong, Sean Wei, additional, Son, Than The, additional, Koh, Ming Hui, additional, Chin, Yi Qing, additional, Nasir, Haziq, additional, Mak, Tze Minn, additional, Hann Chu, Justin Jang, additional, Milton, Donald K., additional, Chow, Vincent T. K., additional, Tambyah, Paul Anantharajah, additional, Chen, Mark, additional, and Wai, Tham Kwok, additional

Published
2021
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24. Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta).

Author

Ong, Sean Wei Xiang, Chiew, Calvin J, Ang, Li Wei, Mak, Tze Minn, Cui, Lin, Toh, Matthias Paul H S, Lim, Yi Ding, Lee, Pei Hua, Lee, Tau Hong, Chia, Po Ying, Maurer-Stroh, Sebastian, Lin, Raymond T P, Leo, Yee Sin, Lee, Vernon J, Lye, David Chien, and Young, Barnaby Edward

Subjects
VIRAL physiology, PUBLIC health surveillance, COVID-19, CONFIDENCE intervals, AGE distribution, RETROSPECTIVE studies, COMPARATIVE studies, SEX distribution, DESCRIPTIVE statistics, ODDS ratio, POLYMERASE chain reaction, LONGITUDINAL method
Abstract

Background The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with wild-type strains from early 2020. Methods National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020. Results A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio [aOR], 4.90; 95% confidence interval [CI]: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI:.95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type). Conclusions B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs. [ABSTRACT FROM AUTHOR]

Published
2022
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25. Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Respiratory Aerosols Emitted by Patients With Coronavirus Disease 2019 (COVID-19) While Breathing, Talking, and Singing.

Author

Coleman, Kristen K, Tay, Douglas Jie Wen, Tan, Kai Sen, Ong, Sean Wei Xiang, Than, The Son, Koh, Ming Hui, Chin, Yi Qing, Nasir, Haziq, Mak, Tze Minn, Chu, Justin Jang Hann, Milton, Donald K, Chow, Vincent T K, Tambyah, Paul Anantharajah, Chen, Mark, and Tham, Kwok Wai

Subjects
AIR microbiology, COVID-19, AEROSOLS, VIRAL load, SINGING, RNA, COMPARATIVE studies, COMMUNICATION, GENES, DESCRIPTIVE statistics, INFECTIOUS disease transmission, RESPIRATION
Abstract

Background Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading events suggest that aerosols play an important role in driving the coronavirus disease 2019 (COVID-19) pandemic. To better understand how airborne SARS-CoV-2 transmission occurs, we sought to determine viral loads within coarse (>5 μm) and fine (≤5 μm) respiratory aerosols produced when breathing, talking, and singing. Methods Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing. Results Thirteen participants (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic and 1 presymptomatic patient. Viral loads ranged from 63–5821 N gene copies per expiratory activity per participant, with high person-to-person variation. Patients earlier in illness were more likely to emit detectable RNA. Two participants, sampled on day 3 of illness, accounted for 52% of total viral load. Overall, 94% of SARS-CoV-2 RNA copies were emitted by talking and singing. Interestingly, 7 participants emitted more virus from talking than singing. Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative. Conclusions Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in SARS-CoV-2 transmission. Exposure to fine aerosols, especially indoors, should be mitigated. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging; whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an urgent enquiry necessitating larger-scale studies. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Positive RT-PCR detected in patients recovered from COVID-19

Author

Tan, Glorijoy Shi En, primary, Ding, Ying, additional, Cui, Lin, additional, Mak, Tze-Minn, additional, Mok, Chee Keng, additional, Kurup, Asok, additional, Parthasarathy, Purnima, additional, Chia, Wan-Ni, additional, Wang, Lin-Fa, additional, Lin, Raymond TP, additional, Leo, Yee-Sin, additional, and Vasoo, Shawn, additional

Published
2021
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27. Viral dynamics and immune correlates of COVID-19 disease severity

Author

Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, and Lye, David Chien

Subjects
immunology, AcademicSubjects/MED00290, Severe acute respiratory syndrome-related coronavirus, SARS-CoV-2, Major Article, viral culture, COVID-19, serology, Humans, Antibodies, Viral, cytokines
Abstract

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of SARS-CoV-2 infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age 46 years, 56% male, 38% with comorbidities). Respiratory samples (n=74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n=30), and plasma samples for levels of inflammatory cytokines and chemokines (n=81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results 57 (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen including 12 (12%) invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB and IL-1RA significantly correlated with disease severity. Conclusion We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offers targets for host-directed immunotherapy which should be evaluated in randomised controlled trials.

Published
2020

28. Human neutralising antibodies elicited by SARS‐CoV‐2 non‐D614G variants offer cross‐protection against the SARS‐CoV‐2 D614G variant

Author

Lee, Cheryl Yi‐Pin, primary, Amrun, Siti Naqiah, additional, Chee, Rhonda Sin‐Ling, additional, Goh, Yun Shan, additional, Mak, Tze‐Minn, additional, Octavia, Sophie, additional, Yeo, Nicholas Kim‐Wah, additional, Chang, Zi Wei, additional, Tay, Matthew Zirui, additional, Torres‐Ruesta, Anthony, additional, Carissimo, Guillaume, additional, Poh, Chek Meng, additional, Fong, Siew‐Wai, additional, Bei, Wang, additional, Lee, Sandy, additional, Young, Barnaby Edward, additional, Tan, Seow‐Yen, additional, Leo, Yee‐Sin, additional, Lye, David C, additional, Lin, Raymond TP, additional, Maurer‐Stroh, Sebastien, additional, Lee, Bernett, additional, Wang, Cheng‐I, additional, Renia, Laurent, additional, and Ng, Lisa FP, additional

Published
2021
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29. Clinical and Virological Features of SARS-CoV-2 Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta)

Author

Ong, Sean Wei Xiang, primary, Chiew, Calvin J., additional, Ang, Li Wei, additional, Mak, Tze-Minn, additional, Cui, Lin, additional, Toh, Matthias Paul HS, additional, Lim, Yi Ding, additional, Lee, Pei Hua, additional, Lee, Tau Hong, additional, Chia, Po Ying, additional, Maurer-Stroh, Sebastian, additional, Lin, Raymond Tzer Pin, additional, Leo, Yee-Sin, additional, Lee, Vernon J., additional, Lye, David Chien, additional, and Young, Barnaby E., additional

Published
2021
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30. Reducing spread of COVID-19 in closed environments: an outbreak investigation and modelling study in dormitory settings

Author

Pung, Rachael, primary, Lin, Bernard, additional, Maurer-Stroh, Sebastian, additional, Sirota, Fernanda L, additional, Mak, Tze Minn, additional, Octavia, Sophie, additional, Pang, Junxiong, additional, Tan, Iain Beehuat, additional, Tan, Clive, additional, Ong, Biauw Chi, additional, Cook, Alex, additional, and Lee, Vernon, additional

Published
2020
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32. Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant

Author

Lee, Cheryl Yi-Pin, primary, Amrun, Siti Naqiah, additional, Chee, Rhonda Sin-Ling, additional, Goh, Yun Shan, additional, Mak, Tze-Minn, additional, Octavia, Sophie, additional, Yeo, Nicholas Kim-Wah, additional, Chang, Zi Wei, additional, Tay, Matthew Zirui, additional, Torres-Ruesta, Anthony, additional, Carissimo, Guillaume, additional, Poh, Chek Meng, additional, Fong, Siew-Wai, additional, Bei, Wang, additional, Lee, Sandy, additional, Young, Barnaby Edward, additional, Tan, Seow-Yen, additional, Leo, Yee-Sin, additional, Lye, David C., additional, Lin, Raymond T. P., additional, Maurer-Stroh, Sebastien, additional, Lee, Bernett, additional, Cheng-I, Wang, additional, Renia, Laurent, additional, and Ng, Lisa F.P., additional

Published
2020
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33. Exportation of Monkeypox Virus From the African Continent

Author

Mauldin, Matthew R, primary, McCollum, Andrea M, additional, Nakazawa, Yoshinori J, additional, Mandra, Anna, additional, Whitehouse, Erin R, additional, Davidson, Whitni, additional, Zhao, Hui, additional, Gao, Jinxin, additional, Li, Yu, additional, Doty, Jeffrey, additional, Yinka-Ogunleye, Adesola, additional, Akinpelu, Afolabi, additional, Aruna, Olusola, additional, Naidoo, Dhamari, additional, Lewandowski, Kuiama, additional, Afrough, Babak, additional, Graham, Victoria, additional, Aarons, Emma, additional, Hewson, Roger, additional, Vipond, Richard, additional, Dunning, Jake, additional, Chand, Meera, additional, Brown, Colin, additional, Cohen-Gihon, Inbar, additional, Erez, Noam, additional, Shifman, Ohad, additional, Israeli, Ofir, additional, Sharon, Melamed, additional, Schwartz, Eli, additional, Beth-Din, Adi, additional, Zvi, Anat, additional, Mak, Tze Minn, additional, Ng, Yi Kai, additional, Cui, Lin, additional, Lin, Raymond T P, additional, Olson, Victoria A, additional, Brooks, Tim, additional, Paran, Nir, additional, Ihekweazu, Chikwe, additional, and Reynolds, Mary G, additional

Published
2020
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34. Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2

Author

Su, Yvonne C. F., primary, Anderson, Danielle E., additional, Young, Barnaby E., additional, Linster, Martin, additional, Zhu, Feng, additional, Jayakumar, Jayanthi, additional, Zhuang, Yan, additional, Kalimuddin, Shirin, additional, Low, Jenny G. H., additional, Tan, Chee Wah, additional, Chia, Wan Ni, additional, Mak, Tze Minn, additional, Octavia, Sophie, additional, Chavatte, Jean-Marc, additional, Lee, Raphael T. C., additional, Pada, Surinder, additional, Tan, Seow Yen, additional, Sun, Louisa, additional, Yan, Gabriel Z., additional, Maurer-Stroh, Sebastian, additional, Mendenhall, Ian H., additional, Leo, Yee-Sin, additional, Lye, David Chien, additional, Wang, Lin-Fa, additional, and Smith, Gavin J. D., additional

Published
2020
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35. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study

Author

Young, Barnaby E, primary, Fong, Siew-Wai, additional, Chan, Yi-Hao, additional, Mak, Tze-Minn, additional, Ang, Li Wei, additional, Anderson, Danielle E, additional, Lee, Cheryl Yi-Pin, additional, Amrun, Siti Naqiah, additional, Lee, Bernett, additional, Goh, Yun Shan, additional, Su, Yvonne C F, additional, Wei, Wycliffe E, additional, Kalimuddin, Shirin, additional, Chai, Louis Yi Ann, additional, Pada, Surinder, additional, Tan, Seow Yen, additional, Sun, Louisa, additional, Parthasarathy, Purnima, additional, Chen, Yuan Yi Constance, additional, Barkham, Timothy, additional, Lin, Raymond Tzer Pin, additional, Maurer-Stroh, Sebastian, additional, Leo, Yee-Sin, additional, Wang, Lin-Fa, additional, Renia, Laurent, additional, Lee, Vernon J, additional, Smith, Gavin J D, additional, Lye, David Chien, additional, and Ng, Lisa F P, additional

Published
2020
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36. Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

Author

Mok, Chee Keng, primary, Ng, Yan Ling, additional, Ahidjo, Bintou Ahmadou, additional, Hua Lee, Regina Ching, additional, Choy Loe, Marcus Wing, additional, Liu, Jing, additional, Tan, Kai Sen, additional, Kaur, Parveen, additional, Chng, Wee Joo, additional, Wong, John Eu-Li, additional, Wang, De Yun, additional, Hao, Erwei, additional, Hou, Xiaotao, additional, Tan, Yong Wah, additional, Mak, Tze Minn, additional, Lin, Cui, additional, Lin, Raymond, additional, Tambyah, Paul, additional, Deng, JiaGang, additional, and Hann Chu, Justin Jang, additional

Published
2020
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37. SARS-CoV-2 Infection among Travelers Returning from Wuhan, China

Author

Ng, Oon-Tek, primary, Marimuthu, Kalisvar, additional, Chia, Po-Ying, additional, Koh, Vanessa, additional, Chiew, Calvin J., additional, De Wang, Liang, additional, Young, Barnaby E., additional, Chan, Monica, additional, Vasoo, Shawn, additional, Ling, Li-Min, additional, Lye, David C., additional, Kam, Kai-qian, additional, Thoon, Koh-Cheng, additional, Kurupatham, Lalitha, additional, Said, Zubaidah, additional, Goh, Ethan, additional, Low, Constance, additional, Lim, Soon-Kok, additional, Raj, Pream, additional, Oh, Olivia, additional, Koh, Valerie T.J., additional, Poh, Cuiqin, additional, Mak, Tze-Minn, additional, Cui, Lin, additional, Cook, Alex R., additional, Lin, Raymond T.P., additional, Leo, Yee-Sin, additional, and Lee, Vernon J.M., additional

Published
2020
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38. A Well Infant With Coronavirus Disease 2019 With High Viral Load

Author

Kam, Kai-qian, primary, Yung, Chee Fu, additional, Cui, Lin, additional, Tzer Pin Lin, Raymond, additional, Mak, Tze Minn, additional, Maiwald, Matthias, additional, Li, Jiahui, additional, Chong, Chia Yin, additional, Nadua, Karen, additional, Tan, Natalie Woon Hui, additional, and Thoon, Koh Cheng, additional

Published
2020
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40. A COVID-19 Nursing Home Cluster Linked to a Household Transmission: An Epidemiological, Clinical and Phylogenetic Investigation

Author

Pang, Junxiong, primary, Tan, Huei Nuo, additional, Mak, Tze Minn, additional, Octavia, Sophie, additional, Maurer-Stroh, Sebastian, additional, Sirota, Fernanda L., additional, Chan, Mark Peng Chew, additional, Leong, Ian Yi Onn, additional, Koh, Valerie TJ, additional, Ooi, Steven Peng Lim, additional, Vasoo, Shawn, additional, Fisher, Dale A., additional, Cui, Lin, additional, Rafman, Heidi, additional, Cutter, Jeffery, additional, and Lee, Vernon J., additional

Published
2020
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41. Association of SARS-CoV-2 Clades with Clinical, Inflammatory and Virologic Outcomes: An Observational Study

Author

Young, Barnaby E., primary, Wei, Wycliffe E., additional, Fong, Siew-Wai, additional, Mak, Tze-Minn, additional, Anderson, Danielle E., additional, Chan, Yi-Hao, additional, Pung, Rachael, additional, Heng, Cheryl SY, additional, Ang, Li Wei, additional, Zheng, Kang Eng, additional, Lee, Bernett, additional, Kalimuddin, Shirin, additional, Pada, Surinder, additional, Tambyah, Paul A., additional, Parthasarathy, Purnima, additional, Tan, Seow-Yen, additional, Sun, Louisa, additional, Smith, Gavin JD, additional, Lin, Raymond Tzer Pin, additional, Leo, Yee-Sin, additional, Renia, Laurent, additional, Wang, Lin-Fa, additional, Ng, Lisa F.P., additional, Maurer-Stroh, Sebastian, additional, Lye, David Chien, additional, and Lee, Vernon J., additional

Published
2020
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42. Immunological and Viral Correlates of COVID-19 Disease Severity: A Prospective Cohort Study of the First 100 Patients in Singapore

Author

Young, Barnaby E., primary, Ong, Sean Wei Xiang, additional, Ng, Lisa FP, additional, Anderson, Danielle E., additional, Chia, Wan Ni, additional, Chia, Po Ying, additional, Ang, Li Wei, additional, Mak, Tze-Minn, additional, Kalimuddin, Shirin, additional, Chai, Louis Yi Ann, additional, Pada, Surinder, additional, Tan, Seow Yen, additional, Sun, Louisa, additional, Parthasarathy, Purmina, additional, Fong, Siew-Wai, additional, Chan, Yi-Hao, additional, Tan, Chee Wah, additional, Lee, Bernett, additional, Rötzschke, Olaf, additional, Ding, Ying, additional, Tambyah, Paul, additional, Low, Jenny GH, additional, Cui, Lin, additional, Barkham, Timothy, additional, Lin, Raymond Tzer Pin, additional, Leo, Yee-Sin, additional, Renia, Laurent, additional, Wang, Lin-Fa, additional, and Lye, David Chien, additional

Published
2020
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43. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity.

Author

Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, and Ding, Ying

Subjects
VIRAL physiology, CYTOKINES, BIOMARKERS, VIRAL pneumonia, INTERLEUKINS, COVID-19, SCIENTIFIC observation, IMMUNOGLOBULINS, VIRAL load, SERODIAGNOSIS, SEROCONVERSION, SEVERITY of illness index, ARTIFICIAL respiration, POLYMERASE chain reaction, CHEMOKINES, VASCULAR endothelial growth factors, LONGITUDINAL method, COMORBIDITY, PLATELET-derived growth factor, MICROBIAL sensitivity tests
Abstract

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Published
2021
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44. Factors influencing SARS-CoV-2 transmission and outbreak control measures in densely populated settings.

Author

Pung, Rachael, Lin, Bernard, Maurer-Stroh, Sebastian, Sirota, Fernanda L., Mak, Tze Minn, Octavia, Sophie, Pang, Junxiong, Tan, Iain Beehuat, Tan, Clive, Ong, Biauw Chi, Cook, Alex R., The Singapore COVID-19 Outbreak Research Team, Tan, Doreen, Chua, Qin Xuan, Chong, Samuel Zeng Rong, Koh, Han Fang, Yap, Elena, Sia, Priscilla, Tan, Ze Ren, and Lee, Fong Sin

Subjects
SARS-CoV-2, RESIDENTS, EPIDEMIOLOGY, SEROLOGY, POPULATION density
Abstract

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore. The aim of the study is to identify combination of factors facilitating SARS-CoV-2 transmission and the impact of control measures in a dormitory through extensive epidemiological, serological and phylogenetic investigations, supported by simulation models. Our findings showed that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak. Furthermore, each resident had about 30 close contacts and each infected resident spread to 4.4 (IQR 3.5–5.3) others at the start of the outbreak. The final attack rate of the current outbreak was 76.2% (IQR 70.6–98.0%) and could be reduced by further 10% under a modified dormitory housing condition. These findings are important when designing living environments in a post COVID-19 future to reduce disease spread and facilitate rapid implementation of outbreak control measures. [ABSTRACT FROM AUTHOR]

Published
2021
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45. Evaluating the effectiveness of the influenza vaccine during respiratory outbreaks in Singapore’s long term care facilities, 2017

Author

Ng, Yixiang, primary, Nandar, Khine, additional, Chua, Lily Ai Vee, additional, Mak, Tze Minn, additional, Foo, Kelly, additional, Muhammad, Imran Roshan, additional, Low, Constance Khia Ki, additional, Ma, Stefan, additional, Ooi, Steven Peng-Lim, additional, Lin, Raymond Tzer Pin, additional, James, Lyn, additional, and Lee, Vernon Jian Ming, additional

Published
2019
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47. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore.

Author

Young, Barnaby Edward, Ong, Sean Wei Xiang, Kalimuddin, Shirin, Low, Jenny G., Tan, Seow Yen, Loh, Jiashen, Ng, Oon-Tek, Marimuthu, Kalisvar, Ang, Li Wei, Mak, Tze Minn, Lau, Sok Kiang, Anderson, Danielle E., Chan, Kian Sing, Tan, Thean Yen, Ng, Tong Yong, Cui, Lin, Said, Zubaidah, Kurupatham, Lalitha, Chen, Mark I-Cheng, and Chan, Monica

Abstract

Key Points: Question: What was the initial experience in Singapore with the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Findings: In this descriptive case series of the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore between January 23 and February 3, 2020, clinical presentation was a respiratory tract infection with prolonged viral shedding from the nasopharynx of 7 days or longer in 15 patients (83%). Supplemental oxygen was required in 6 patients (33%), 5 of whom were treated with lopinavir-ritonavir, with variable clinical outcomes following treatment. Meaning: These findings provide clinical features and course among patients diagnosed with SARS-CoV-2 infection in Singapore. Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China. Objective: To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management. Design, Setting, and Participants: Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020. Exposures: Confirmed SARS-CoV-2 infection. Main Outcomes and Measures: Clinical, laboratory, and radiologic data were collected, including PCR cycle threshold values from nasopharyngeal swabs and viral shedding in blood, urine, and stool. Clinical course was summarized, including requirement for supplemental oxygen and intensive care and use of empirical treatment with lopinavir-ritonavir. Results: Among the 18 hospitalized patients with PCR-confirmed SARS-CoV-2 infection (median age, 47 years; 9 [50%] women), clinical presentation was an upper respiratory tract infection in 12 (67%), and viral shedding from the nasopharynx was prolonged for 7 days or longer among 15 (83%). Six individuals (33%) required supplemental oxygen; of these, 2 required intensive care. There were no deaths. Virus was detectable in the stool (4/8 [50%]) and blood (1/12 [8%]) by PCR but not in urine. Five individuals requiring supplemental oxygen were treated with lopinavir-ritonavir. For 3 of the 5 patients, fever resolved and supplemental oxygen requirement was reduced within 3 days, whereas 2 deteriorated with progressive respiratory failure. Four of the 5 patients treated with lopinavir-ritonavir developed nausea, vomiting, and/or diarrhea, and 3 developed abnormal liver function test results. Conclusions and Relevance: Among the first 18 patients diagnosed with SARS-CoV-2 infection in Singapore, clinical presentation was frequently a mild respiratory tract infection. Some patients required supplemental oxygen and had variable clinical outcomes following treatment with an antiretroviral agent. This case series describes the epidemiologic features, clinical presentation, treatment, and outcomes of the first 18 patients with confirmed coronavirus disease 2019 (COVID-19) in Singapore [ABSTRACT FROM AUTHOR]

Published
2020
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