Evidence of SARS-Cov-2 Infection in Returning Travelers from Wuhan, China

The new england journal of medicine

Correspondence

Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China

To the Editor: As the number of cases of infec- to Germersheim, Germany, and quarantined for tion with the novel coronavirus (SARS-CoV-2) 14 days, since this period is thought to be the has continued to increase, many countries have upper limit of the incubation period of SARS- established restrictions regarding travelers who CoV-2. Screening for symptoms and clinical signs have recently visited China.1 With lockdown of infection was performed before their depar- measures imposed in Hubei Province, China,2 ture from China. A total of 126 travelers were and a public health emergency of international allowed to board an aircraft operated by the concern declared by the World Health Organiza- German air force (Fig. 1). tion,3 foreign nationals have sought to return During the flight, 10 passengers were isolated. to their home countries from China, and public Two passengers had had contact with 1 person health authorities are racing to contain the spread who had a confirmed case of SARS-CoV-2 infec- of Covid-19 (the disease caused by SARS-CoV-2 tion, 6 had reported symptoms, were deemed to infection) around the world. This process is com- be clinically symptomatic, or both, and 2 pas- plicated by epidemiologic uncertainty regarding sengers had accompanied family members who possible transmission of the virus by asymptom- had been isolated on the flight because of sus- atically or subclinically symptomatic infected pected SARS-CoV-2 infection or because of other persons. It is unclear whether persons who show symptoms (i.e., symptoms related to pregnancy). no signs or symptoms of respiratory infection These 10 passengers were transferred to Univer- shed SARS-CoV-2. sity Hospital Frankfurt immediately after arrival. In this context, a group of predominantly All 10 tested negative for SARS-CoV-2 by real-time German nationals who had stayed in Hubei reverse-transcription–polymerase-chain-reaction Province was evacuated to Frankfurt, Germany, (RT-PCR) assays4 of throat swabs and sputum. on February 1, 2020. They were to be transferred The remaining 116 passengers (5 months to 68 years of age), including 23 children, were sent to the medical assessment center at Frankfurt this week's letters Airport, where each was evaluated by a medical 1278 Evidence of SARS-CoV-2 Infection in Returning team of physicians. Each passenger was asked to Travelers from Wuhan, China report current symptoms of fever, fatigue, sore throat, cough, runny nose, muscle aches, and 1280 Telacebec (Q203), a New Antituberculosis Agent diarrhea, and each one was screened for signs of 1282 MRI Screening in Women with Dense Breasts infection in the nose and throat. The tempera- ture of all passengers was taken. All were afe- 1285 A Modified Vaccine against Smallpox brile except for 1 passenger who had a tempera- ture of 38.4°C and reported dyspnea and cough. 1286 Cabazitaxel in Metastatic Prostate Cancer He was transferred to University Hospital Frank- e24 Lay Responder Care for the Adult Victim of Out- furt for evaluation. However, testing to detect of-Hospital Cardiac Arrest SARS-CoV-2 by RT-PCR of a throat swab and sputum was negative.

126 Passengers boarded aircraft in Wuhan

2 Had known contact with person with confirmed case of SARS-CoV-2 but tested negative for SARS-CoV-2 by RT-PCR of throat swab and sputum

6 Were deemed symptomatic 10 Were transferred to hospital on the flight but tested negative on arrival in Germany for SARS-CoV-2 by RT-PCR of throat swab and sputum

2 Had accompanied persons with suspected SARS-CoV-2 infection or other health problems but tested negative for the infection by RT-PCR of throat swab and sputum

116 Proceeded to medical assessment center

1 Was deemed symptomatic but tested negative for SARS-CoV-2 by RT-PCR of throat swab and sputum

115 Were deemed asymptomatic but were offered SARS-CoV-2 testing

1 Declined to be tested

114 Underwent testing for 112 Had negative test results SARS-CoV-2 by for SARS-CoV-2 RT-PCR of throat swab

2 Had confirmed positive test results for SARS-CoV-2

Figure 1. Evaluation and Testing of Passengers. Passengers were evaluated to detect infection with the novel coronavirus (SARS-CoV-2) after their flight from Wuhan, China, to Frankfurt, Germany. All tests were targeted to detect SARS-CoV-2.

In addition to the preplanned multistep pro- protocol consisting of two commercial sets cess of screening for signs and symptoms of (LightMix Modular SARS and Wuhan CoV E-gene, infection and observing the asymptomatic co- and LightMix Modular Wuhan CoV RdRP-gene, hort in quarantine, we decided to offer a throat both produced by TIB MOLBIOL) and retesting swab to test for SARS-CoV-2 in each of the 115 of the positive samples at the Institute of Virol- travelers who had passed triage. A total of 114 ogy, Philipps University Marburg, in Marburg, passengers consented to the test. Germany, confirmed the results. In addition, the Two of the 114 persons (1.8%) in this cohort isolation of SARS-CoV-2 from both samples in of travelers who had passed the symptoms-based cell culture of Caco-2 cells indicated potential screening tested positive for SARS-CoV-2 by RT-PCR infectivity (see the Supplementary Appendix, avail- (cycle threshold value in the two samples, 24.39 able with the full text of this letter at NEJM.org). and 30.25, respectively). Testing with a second These two persons were subsequently isolated

n engl j med 382;13 nejm.org March 26, 2020 The New England Journal of Medicine Downloaded from nejm.org on March 28, 2020. For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. The new england journal of medicine from the cohort and transferred to the Infec- Markus Eickmann, Ph.D. tious Disease Unit at University Hospital Frank- Philipps University Marburg furt for further evaluation and observation on Marburg, Germany the following day. After a thorough evaluation in Maria J.G.T. Vehreschild, M.D. the hospital ward, a faint rash and minimal Gerrit Kann, M.D. pharyngitis were observed in one patient. Both Timo Wolf, M.D. patients remained well and afebrile 7 days after University Hospital Frankfurt admission. Frankfurt am Main, Germany In this effort to evacuate 126 people from René Gottschalk, M.D., Ph.D. Wuhan to Frankfurt, a symptom-based screening Health Protection Authority, City of Frankfurt process was ineffective in detecting SARS-CoV-2 Frankfurt am Main, Germany infection in 2 persons who later were found to have evidence of SARS-CoV-2 in a throat swab. Sandra Ciesek, M.D. We discovered that shedding of potentially infec- University Hospital Frankfurt Frankfurt am Main, Germany tious virus may occur in persons who have no fe- [email protected] ver and no signs or only minor signs of infection. Disclosure forms provided by the authors are available with Sebastian Hoehl, M.D. the full text of this letter at NEJM.org. Holger Rabenau, Ph.D. This letter was published on February 18, 2020, and updated on Annemarie Berger, Ph.D. February 20, 2020, at NEJM.org. Marhild Kortenbusch 1. Stevenson A. China increasingly walled off as countries seek Jindrich Cinatl, Ph.D. to stem coronavirus. New York Times. February 1, 2020 (https:// www.nytimes.com/2020/02/01/world/asia/china-coronavirus-us Denisa Bojkova, M.Sc. -australia.html). University Hospital Frankfurt 2. BBC News. China coronavirus: lockdown measures rise Frankfurt am Main, Germany across Hubei province. January 23, 2020 (https://www.bbc.com/ Pia Behrens, M.D. news/world-asia-china-51217455). 3. World Health Organization. Statement on the second meeting Boris Böddinghaus, M.D. of the International Health Regulations (2005) Emergency Com- Udo Götsch, M.D. mittee regarding the outbreak of novel coronavirus (2019-nCoV). Frank Naujoks, M.D. January 30, 2020 (https://www.who .int/ news - room/ detail/ 30 - 01 -2020 - statement - on - the - second - meeting - of - the - international Peter Neumann, M.D. -health-regulations-(2005)-emergency-committee-regarding-the Joscha Schork, M.D. -outbreak - of - novel - coronavirus - (2019 - ncov)). Petra Tiarks-Jungk, M.D. 4. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Sur- Antoni Walczok, M.D. veill 2020;25(3):2000045. Health Protection Authority, City of Frankfurt Frankfurt am Main, Germany DOI: 10.1056/NEJMc2001899

Telacebec (Q203), a New Antituberculosis Agent

To the Editor: Shortly after the discovery of tent agents and massive efforts toward tubercu- streptomycin in 1943, it became clear that suc- losis control, the disease that once killed one in cessful treatment of tuberculosis and prevention four persons became a seemingly distant threat of drug resistance required a combination of at in many countries. However, an increasing prev- least three effective drugs. What followed in the alence of drug resistance has made the goal of 1950s was the introduction of triple therapy with global elimination of tuberculosis a far-removed streptomycin, aminosalicylic acid, and isoniazid, prospect once more. New drugs and regimens the so-called 100% effective regimen and a major are needed to ensure continued progress toward milestone on the path to modern antimicrobial this goal. therapy.1,2 Telacebec (Q203) is a novel first-in-class anti- After the stepwise introduction of more po- tuberculosis drug that targets Mycobacterium tuber-