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      SARS-CoV-2 Infection among Travelers Returning from Wuhan, China

      letter
      , M.P.H. , , M.B., B.S., , M.B., B.S., , Ph.D. , M.P.H. , M.Sc., , M.B., B.Chir., , B.M., B.S., , M.B., B.S., , M.B., B.S.,   , M.B., B.S. , M.Med.(Ped.), , M.Med.(Ped.) , M.P.H., , M.P.H., , M.P.H., , M.P.H., , M.P.H., , M.P.H., , Ph.D., , M.P.H., , M.P.H. , Ph.D., , Ph.D. , Ph.D. , M.B., B.S., , M.P.H. , Ph.D.
      The New England Journal of Medicine
      Massachusetts Medical Society
      Keyword part (code): 18Keyword part (keyword): Infectious DiseaseKeyword part (code): 18_1Keyword part (keyword): Infectious Disease GeneralKeyword part (code): 18_6Keyword part (keyword): Viral InfectionsKeyword part (code): 18_9Keyword part (keyword): Global HealthKeyword part (code): 18_10Keyword part (keyword): Diagnostics , 18, Infectious Disease, Keyword part (code): 18_1Keyword part (keyword): Infectious Disease GeneralKeyword part (code): 18_6Keyword part (keyword): Viral InfectionsKeyword part (code): 18_9Keyword part (keyword): Global HealthKeyword part (code): 18_10Keyword part (keyword): Diagnostics , 18_1, Infectious Disease General, 18_6, Viral Infections, 18_9, Global Health, 18_10, Diagnostics

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          Abstract

          To the Editor: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections (causing coronavirus disease 2019 [Covid-19]) spread globally, uncertainty surrounds estimates of the true number of infected persons, which is crucial to determining the severity of infection and the incidence of mild or asymptomatic cases and their possible transmission. 1 Modeling estimates suggest that in Wuhan, China, the city with the most Covid-19 cases, there are substantially more cases than were officially reported, because milder cases may not have been captured in hospital-based surveillance. 2,3 Data on travelers returning from areas with cases of Covid-19 could be useful in estimating its incidence. 4 We followed up on 94 persons who boarded an evacuation flight from Wuhan to Singapore on January 30, 2020. Screening for body temperature was conducted at check-in and before boarding, and 3 febrile persons were prevented from boarding (Figure 1); no additional information regarding the status of these 3 febrile persons was available. Surgical masks were provided to passengers on board the plane. On arrival in Singapore, the passengers underwent repeat screening for body temperature (fever was defined as a body temperature ≥38°C), and 2 persons (a woman 48 years of age [Patient 1] and a woman 47 years of age [Patient 2]) had a fever. The 2 febrile women were transferred immediately to a hospital, and they tested positive for SARS-CoV-2 (their clinical course is described in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The remaining 92 afebrile passengers (age range, 2 to 82 years) were quarantined for 14 days at a government quarantine facility, where they were checked for symptoms and fever three times daily. Six persons reported symptoms (4 on quarantine day 2 and 2 on quarantine day 3) and were placed in isolation in a hospital and underwent polymerase-chain-reaction (PCR) testing; all 6 persons tested negative for SARS-CoV-2. On quarantine day 3, samples from 76 of the 86 asymptomatic persons (75 nasopharyngeal swab samples and 1 nasal swab sample) were obtained and tested by means of PCR assay. A 17-year-old boy (the son of Patient 1) tested positive for Covid-19 and continued to have PCR-positive status for 2 weeks, and a 41-year-old man had an inconclusive result (positive for N gene and negative for ORF1ab gene). On quarantine day 6, samples from all 87 quarantined asymptomatic persons (85 nasopharyngeal swab samples and 2 nasal swab samples [3 of the 6 persons who had been transferred to the hospital before February 2 had returned to the government quarantine facility]) were obtained and tested; all tested negative. All persons who were not isolated in the hospital were released from quarantine on day 14, and all remained uninfected with Covid-19. Understanding the implications of transmission of SARS-CoV-2 infection from persons with asymptomatic or very mild symptomatic cases of Covid-19 is vital for the formulation of containment strategies.

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          Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study

          Summary Background Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. Methods We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23–24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). Findings In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47–2·86) and that 75 815 individuals (95% CrI 37 304–130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8–7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227–805), 113 (57–193), 98 (49–168), 111 (56–191), and 80 (40–139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1–2 weeks. Interpretation Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. Funding Health and Medical Research Fund (Hong Kong, China).
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            Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China

            To the Editor: As the number of cases of infection with the novel coronavirus (SARS-CoV-2) has continued to increase, many countries have established restrictions regarding travelers who have recently visited China. 1 With lockdown measures imposed in Hubei Province, China, 2 and a public health emergency of international concern declared by the World Health Organization, 3 foreign nationals have sought to return to their home countries from China, and public health authorities are racing to contain the spread of Covid-19 (the disease caused by SARS-CoV-2 infection) around the world. This process is complicated by epidemiologic uncertainty regarding possible transmission of the virus by asymptomatically or subclinically symptomatic infected persons. It is unclear whether persons who show no signs or symptoms of respiratory infection shed SARS-CoV-2. In this context, a group of predominantly German nationals who had stayed in Hubei Province was evacuated to Frankfurt, Germany, on February 1, 2020. They were to be transferred to Germersheim, Germany, and quarantined for 14 days, since this period is thought to be the upper limit of the incubation period of SARS-CoV-2. Screening for symptoms and clinical signs of infection was performed before their departure from China. A total of 126 travelers were allowed to board an aircraft operated by the German air force (Figure 1). During the flight, 10 passengers were isolated. Two passengers had had contact with 1 person who had a confirmed case of SARS-CoV-2 infection, 6 had reported symptoms, were deemed to be clinically symptomatic, or both, and 2 passengers had accompanied family members who had been isolated on the flight because of suspected SARS-CoV-2 infection or because of other symptoms (i.e., symptoms related to pregnancy). These 10 passengers were transferred to University Hospital Frankfurt immediately after arrival. All 10 tested negative for SARS-CoV-2 by real-time reverse-transcription–polymerase-chain-reaction (RT-PCR) assays 4 of throat swabs and sputum. The remaining 116 passengers (5 months to 68 years of age), including 23 children, were sent to the medical assessment center at Frankfurt Airport, where each was evaluated by a medical team of physicians. Each passenger was asked to report current symptoms of fever, fatigue, sore throat, cough, runny nose, muscle aches, and diarrhea, and each one was screened for signs of infection in the nose and throat. The temperature of all passengers was taken. All were afebrile except for 1 passenger who had a temperature of 38.4°C and reported dyspnea and cough. He was transferred to University Hospital Frankfurt for evaluation. However, testing to detect SARS-CoV-2 by RT-PCR of a throat swab and sputum was negative. In addition to the preplanned multistep process of screening for signs and symptoms of infection and observing the asymptomatic cohort in quarantine, we decided to offer a throat swab to test for SARS-CoV-2 in each of the 115 travelers who had passed triage. A total of 114 passengers consented to the test. Two of the 114 persons (1.8%) in this cohort of travelers who had passed the symptoms-based screening tested positive for SARS-CoV-2 by RT-PCR (cycle threshold value in the two samples, 24.39 and 30.25, respectively). Testing with a second protocol consisting of two commercial sets (LightMix Modular SARS and Wuhan CoV E-gene, and LightMix Modular Wuhan CoV RdRP-gene, both produced by TIB MOLBIOL) and retesting of the positive samples at the Institute of Virology, Philipps University Marburg, in Marburg, Germany, confirmed the results. In addition, the isolation of SARS-CoV-2 from both samples in cell culture of Caco-2 cells indicated potential infectivity (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). These two persons were subsequently isolated from the cohort and transferred to the Infectious Disease Unit at University Hospital Frankfurt for further evaluation and observation on the following day. After a thorough evaluation in the hospital ward, a faint rash and minimal pharyngitis were observed in one patient. Both patients remained well and afebrile 7 days after admission. In this effort to evacuate 126 people from Wuhan to Frankfurt, a symptom-based screening process was ineffective in detecting SARS-CoV-2 infection in 2 persons who later were found to have evidence of SARS-CoV-2 in a throat swab. We discovered that shedding of potentially infectious virus may occur in persons who have no fever and no signs or only minor signs of infection.
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              Author and article information

              Journal
              N Engl J Med
              N. Engl. J. Med
              nejm
              The New England Journal of Medicine
              Massachusetts Medical Society
              0028-4793
              1533-4406
              12 March 2020
              : NEJMc2003100
              Affiliations
              National Centre for Infectious Diseases, Singapore, Singapore oon_tek_ng@ 123456ncid.sg
              kalisvar_marimuthu@ 123456ncid.sg
              Ministry of Health, Singapore, Singapore
              National Centre for Infectious Diseases, Singapore, Singapore
              KK Women’s and Children’s Hospital, Singapore, Singapore
              Ministry of Health, Singapore, Singapore
              National Centre for Infectious Diseases, Singapore, Singapore
              Saw Swee Hock School of Public Health, Singapore, Singapore
              National Centre for Infectious Diseases, Singapore, Singapore yee_sin_leo@ 123456ncid.sg
              Ministry of Health, Singapore, Singapore vernon_lee@ 123456moh.gov.sg
              Author information
              http://orcid.org/0000-0003-1010-2230
              http://orcid.org/0000-0002-2402-7262
              Article
              NJ202003123821503
              10.1056/NEJMc2003100
              7121487
              32163698
              18e3b68f-87df-42f2-b1ad-03f5bd90dd79
              Copyright © 2020 Massachusetts Medical Society. All rights reserved.

              This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.

              History
              Funding
              Funded by: National Medical Research Council, FundRef http://dx.doi.org/10.13039/501100001349;
              Award ID: CGAug16C005
              Award ID: MOH-000276
              Award ID: MOH-CIRG18nov-0006
              Categories
              Correspondence
              Custom metadata
              2020-03-12T12:00:00-04:00
              2020
              03
              12
              12
              00
              00
              -04:00

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