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      Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study

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          Summary

          Background

          Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful.

          Methods

          We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [ R 0] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R 0 value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures.

          Findings

          For the baseline scenario, when R 0 was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R 0 was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R 0 was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R 0 was 1·5, by 93·0% (81·5–99·7) when R 0 was 2·0, and by 78·2% (59·0 −94·4) when R 0 was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R 0 of 1·5.

          Interpretation

          Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines.

          Funding

          Singapore Ministry of Health, Singapore Population Health Improvement Centre.

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          Most cited references18

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

            Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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              Is Open Access

              Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

              Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                23 March 2020
                23 March 2020
                Affiliations
                [a ]Saw Swee Hock School of Public Health, National University of Singapore, Singapore
                [b ]London School of Hygiene & Tropical Medicine, London, UK
                Author notes
                [* ]Correspondence to: Dr Alex R Cook, Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549 alex.richard.cook@ 123456gmail.com
                Article
                S1473-3099(20)30162-6
                10.1016/S1473-3099(20)30162-6
                7158571
                32213332
                a86db856-488a-4286-803d-cdc4e8d255ce
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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