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Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore

Educational Objective
Review key information from the COVID-19 outbreak in Signapore
1 Credit CME
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.

Abstract

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.

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Article Information

Corresponding Authors: Barnaby Edward Young, MB, BChir (Barnaby_young@ncid.sg) and Yee-Sin Leo, MPH (Yee_Sin_Leo@ncid.sg), National Centre for Infectious Diseases, 16 Jln Tan Tock Seng, Singapore 308442.

Accepted for Publication: February 27, 2020.

Published Online: March 3, 2020. doi:10.1001/jama.2020.3204

Correction: This article was corrected online on March 20, 2020, for an incorrect medication dose in the text, a typographic error in Figure 1, and an error in the author affiliations.

Author Contributions: Dr Young had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Young, Ong, O.-T. Ng, Marimuthu, Ang, Anderson, M. Chan, Vasoo, B. Tan, Leo, Lye.

Acquisition, analysis, or interpretation of data: Young, Ong, Kalimuddin, Low, S. Tan, Loh, O.-T. Ng, Marimuthu, Ang, Mak, Lau, Anderson, K. Chan, T. Tan, T. Ng, Cui, Said, Kurupatham, Chen, Wang, B. Tan, Lin, Lee, Leo, Lye.

Drafting of the manuscript: Young, Ong, Low, O.-T. Ng, Ang, Mak, Anderson, Said, Lee, Lye.

Critical revision of the manuscript for important intellectual content: Young, Ong, Kalimuddin, Low, S. Tan, Loh, O.-T. Ng, Marimuthu, Lau, Anderson, K. Chan, T. Tan, T. Ng, Cui, Said, Kurupatham, Chen, M. Chan, Vasoo, Wang, B. Tan, Lin, Lee, Leo, Lye.

Statistical analysis: Young, Ang, Anderson, Said.

Obtained funding: Young, Marimuthu, Anderson, B. Tan.

Administrative, technical, or material support: Young, Ong, S. Tan, O.-T. Ng, Marimuthu, Mak, Lau, Anderson, K. Chan, T. Ng, Cui, Said, Kurupatham, Chen, M. Chan, Vasoo, Lin, Wang, B. Tan, Lee, Leo, Lye.

Supervision: Young, Kalimuddin, O.-T. Ng, Marimuthu, Anderson, T. Ng, M. Chan, Vasoo, Lin, Wang, B. Tan, Lee, Leo, Lye.

Conflict of Interest Disclosures: Dr Young reported receiving personal fees from Sanofi and Roche. Dr Wang reported receiving grants from the Ministry of Health, Singapore. No other disclosures were reported.

Funding/Support: Recruitment of study participants and sample collection was funded by a seed grant from the Singapore National Medical Research Council (TR19NMR119SD [project CCGSFPOR20001]). The polymerase chain reaction work on nonrespiratory clinical samples was partially supported by grant NRF2016NRFNSFC002-013 (Combating the Next SARS-or MERS-Like Emerging Infectious Disease Outbreak by Improving Active Surveillance).

Role of the Funder/Sponsor: The Singapore National Medical Research Council had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank all clinical and nursing staff who provided care for the patients at National Centre for Infectious Diseases, Singapore General Hospital, Changi General Hospital, and Sengkang General Hospital; staff at the Communicable Diseases Division, Ministry of Health, for contributing to outbreak response and contact tracing; staff at the National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, for assisting with data analysis; staff in the Singapore Infectious Disease Clinical Research Network and Infectious Disease Research and Training Office, National Centre for Infectious Diseases, for coordinating patient recruitment; staff (especially Jin Phang Loh, PhD, Wee Hong Koh, BSc, Ai Sim Lim, BSc, Xiao Fang Lim, BSc, and Chin Wen Liaw, BSc, at DSO National Laboratories) for BSL3 laboratory work; staff at Duke NUS Medical School (especially Viji Vijayan, MBBS, Velraj Sivalingam, BSc, and Benson Ng, BSc, of the Duke-NUS ABSL3 facility) for logistics management and assistance. None of these individuals received compensation for their role in the study.

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