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      Early dynamics of transmission and control of COVID-19: a mathematical modelling study

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      , PhD a , * , , PhD a , , MSc a , , PhD a , , PhD a , , PhD a , , PhD a , Centre for Mathematical Modelling of Infectious Diseases COVID-19 working group
      The Lancet. Infectious Diseases
      The Author(s). Published by Elsevier Ltd.

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          Summary

          Background

          An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced.

          Methods

          We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020.

          Findings

          We estimated that the median daily reproduction number ( R t) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of R t, assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population.

          Interpretation

          Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually.

          Funding

          Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.

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          Most cited references11

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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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            Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

            To the Editor: The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world. 1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient. A 33-year-old otherwise healthy German businessman (Patient 1) became ill with a sore throat, chills, and myalgias on January 24, 2020. The following day, a fever of 39.1°C (102.4°F) developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26 (index patient in Figure 1) (see Supplementary Appendix, available at NEJM.org, for details on the timeline of symptom development leading to hospitalization). On January 27, she informed the company about her illness. Contact tracing was started, and the above-mentioned colleague was sent to the Division of Infectious Diseases and Tropical Medicine in Munich for further assessment. At presentation, he was afebrile and well. He reported no previous or chronic illnesses and had no history of foreign travel within 14 days before the onset of symptoms. Two nasopharyngeal swabs and one sputum sample were obtained and were found to be positive for 2019-nCoV on quantitative reverse-transcriptase–polymerase-chain-reaction (qRT-PCR) assay. 2 Follow-up qRT-PCR assay revealed a high viral load of 108 copies per milliliter in his sputum during the following days, with the last available result on January 29. On January 28, three additional employees at the company tested positive for 2019-nCoV (Patients 2 through 4 in Figure 1). Of these patients, only Patient 2 had contact with the index patient; the other two patients had contact only with Patient 1. In accordance with the health authorities, all the patients with confirmed 2019-nCoV infection were admitted to a Munich infectious diseases unit for clinical monitoring and isolation. So far, none of the four confirmed patients show signs of severe clinical illness. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. 3 The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak. In this context, the detection of 2019-nCoV and a high sputum viral load in a convalescent patient (Patient 1) arouse concern about prolonged shedding of 2019-nCoV after recovery. Yet, the viability of 2019-nCoV detected on qRT-PCR in this patient remains to be proved by means of viral culture. Despite these concerns, all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes. Since hospital capacities are limited — in particular, given the concurrent peak of the influenza season in the northern hemisphere — research is needed to determine whether such patients can be treated with appropriate guidance and oversight outside the hospital.
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              Is Open Access

              Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020

              Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.
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                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                The Author(s). Published by Elsevier Ltd.
                1473-3099
                1474-4457
                11 March 2020
                11 March 2020
                Affiliations
                [a ]Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK
                Author notes
                [* ]Correspondence to: Dr Adam J Kucharski, Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK adam.kucharski@ 123456lshtm.ac.uk
                [†]

                Members are listed in the appendix

                Article
                S1473-3099(20)30144-4
                10.1016/S1473-3099(20)30144-4
                7158569
                32171059
                407e1b95-7fb9-4f46-a93a-fe735f7b0e00
                © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                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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