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new england journal
n engl j med 382;10 March 5, 2020
Cor responde nce
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 spread-
ing around the world.
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 re-
porting 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 busi-
nessman (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) devel-
oped, 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 Januar y 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 posi-
tive for 2019-nCoV on January 26 (index patient
in Fig. 1) (see Supplementary Appendix, available
at, for details on the timeline of symp-
tom 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 re-
ported 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.
Follow-up qRT-
PCR assay revealed a high viral load of 10
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 (Pa-
tients 2 through 4 in Fig. 1). Of these patients,
only Patient 2 had contact with the index patient;
the other t wo patients had contact only with
Patient 1. In accordance with the health au-
thorities, all the patients with conf irmed 2019-
nCoV infection were admitted to a Munich infec-
tious diseases unit for clinical monitoring and
isolation. So far, none of the four conf irmed
patients show signs of severe clinical illness.
This case of 2019-nCoV infection was diag-
nosed 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.
The fact that asymptomatic persons are po-
tential sources of 2019-nCoV infection may war-
this week's letters
970 Transmission of 2019-nCoV Infection from an
Asymptomatic Contact in Germany
972 Dapagliflozin in Patients with Heart Failure and
Reduced Ejection Fraction
974 A Smartwatch to Identify Atrial Fibrillation
976 Focused Cardiac Ultrasonography for Left
Ventricular Systolic Function
The New England Journal of Medicine
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Copyright © 2020 Massachusetts Medical Society. All rights reserved.
Cor re spondence
n engl j med 382;10 March 5, 2020
rant a reassessment of transmission dynamics of
the current outbreak. In this context, the detec-
tion of 2019-nCoV and a high sputum viral load
in a convalescent patient (Patient 1) arouse con-
cern 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 hemi-
sphere — research is needed to determine
whether such patients can be treated with ap-
propriate guidance and oversight outside the
Camilla Rothe, M.D.
Mirjam Schunk, M.D.
Peter Sothmann, M.D.
Gisela Bretzel, M.D.
Guenter Froeschl, M.D.
Claudia Wallrauch, M.D.
Thorbjörn Zimmer, M.D.
Verena Thiel, M.D.
Christian Janke, M.D.
University Hospital LMU Munich
Munich, Germany
Wolfgang Guggemos, M.D.
Michael Seilmaier, M.D.
Klinikum Mü nchen-Schwabing
Munich, Germany
Christian Drosten, M.D.
Charité Universitätsmedizin Berlin
Berlin, Germany
Patrick Vollmar, M.D.
Katrin Zwirglmaier, Ph.D.
Sabine Zange, M.D.
Roman Wölfel, M.D.
Bundeswehr Institute of Microbiology
Munich, Germany
Michael Hoelscher, M.D., Ph.D.
University Hospital LMU Munich
Munich, Germany
Disclosure forms provided by the authors are avail able wit h
the fu ll text of th is letter at
This letter was published on Januar y 30, 2020, and updated on
February 6, 2020, at
1 . Zhu N, Zhang D, Wang W, et al. A novel coronavi rus f rom
patient s with pneumonia in China, 2019. N Engl J Med 2020; 382:
2 . Corman V, Bleicker T, Brün ink S, et al. Diag nostic detec-
tion of Wuha n coronavirus 2019 by rea l-time RT-PCR. Geneva:
World Health Organizat ion, January 13, 2020 (https://w ww
. who . int/ docs/ default - source/ coronaviruse/ wuhan - vi rus - assay
- v1991527e5122341d99287a1b17c111902 . pdf).
3 . Callaway E, Cyranosk i D. China coronavirus: si x questions
scientists are asking. Nature 2020; 577: 605-7.
DOI: 10.1056/NEJMc2001468
Figure 1. Timeline of Exposure to Index Patient with Asymptomatic 2019-CoV Infection in Germany.
Patient 1 Attended business
Positive PCR
Patient 2 Attended business
Positive PCR
Index Patient
Attended business
SymptomsVisit to Germany
Flight to
Positive PCR
Patient 3 Symptoms
Positive PCR
Patient 4
Positive PCR
Contact with Patient 1
The New England Journal of Medicine
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Copyright © 2020 Massachusetts Medical Society. All rights reserved.
... This patient had no symptoms but ground-glass lung opacities were detected in radiography [14]. Also, in a report from Germany, transmission of COVID-19 after probable direct contact with asymptomatic subjects was mentioned [15]. In previous reports about SARS and MERS, asymptomatic patients reached 7.5 % and 25% respectively [16,17]. ...
... In previous reports about SARS and MERS, asymptomatic patients reached 7.5 % and 25% respectively [16,17]. Weak immune response or other routes of transmission may possibly influence asymptomatic presentation of COVID-19 [15,18]. Whether the fecal-oral route plays a role in this respect calls for further investigation. ...
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COVID-19 is a worldwide public health problem that has attracted much attention due to its clinical and para-clinical findings. In the western Asia, Qom was the first city to report COVID-19 cases on a large scale. We report gastrointestinal (GI) manifestations, as the only primary signs of COVID-19 infection have been reported.
... Indeed, SARS-CoV-2 can spread from person-to-person in an efficient and sustained way by coughing and sneezing. Moreover, this coronavirus can spread from seemingly healthy carriers or people who had not yet developed symptoms [6]. Experiment suggests that SARS-CoV-2 may have the potential to be transmitted through aerosols [7][8][9][10][11]. ...
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Converging lines of evidence seem to indicate that SARS-CoV-2, the novel coronavirus responsible for the COVID-19 pandemic, can be transmitted from person-to-person via aerosols that waft through the air and accumulate over time. The airborne nature of the virus could be a threat in indoor spaces in general and in particular for in-class education. We provide an assessment of the risk of SARS-CoV-2 infection during a 7-hour school day in elementary schools. We show that existing data are insufficient to establish a low (below 1%) probability of infection with high accuracy. The use of facemasks and social distancing could significantly decrease this risk.
... Although the transmission of the virus is not well understood" several studies have reported some possible ways of transmission, such as importation and human-to-human transmission in Vietnam [9] and person-to-person transmission [10]. Other studies in which the transmission of COVID-19 has been investigated include the transmission of the infection from an asymptomatic contact [11], prediction of international and domestic blowout of 2019-nCoV outbreak from Wuhan [12,13], and early dynamic spread of pneumonia coronavirus disease in Wuhan, China [14]. A fractional approach to modeling this complex system was proposed in [15] where contact tracing, among others, was a key factor in mitigating the spread of the virus. ...
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Coronaviruses are types of viruses that are widely spread in humans, birds, and other mammals, leading to hepatic, respiratory, neurologic, and enteric diseases. The disease is presently a pandemic with great medical, economical, and political impacts, and it is mostly spread through physical contact. To extinct the virus, keeping physical distance and taking vaccine are key. In this study, a dynamical transmission compartment model for coronavirus (COVID-19) is designed and rigorously analyzed using Routh–Hurwitz condition for the stability analysis. A global dynamics of mathematical formulation was investigated with the help of a constructed Lyapunov function. We further examined parameter sensitivities (local and global) to identify terms with greater impact or influence on the dynamics of the disease. Our approach is data driven to test the efficacy of the proposed model. The formulation was incorporated with available confirmed cases from January 22, 2020, to December 20, 2021, and parameterized using real-time series data that were collected on a daily basis for the first 705 days for fourteen countries, out of which the model was simulated using four selected countries: USA, Italy, South Africa, and Nigeria. A least square technique was adopted for the estimation of parameters. The simulated solutions of the model were analyzed using MAPLE-18 with Runge–Kutta–Felberg method (RKF45 solver). The model entrenched parameters analysis revealed that there are both disease-free and endemic equilibrium points. The solutions depicted that the free equilibrium point for COVID-19 is asymptotic locally stable, when the epidemiological reproduction number condition (R0<1)\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$(R_{0}<1)$$\end{document}. The simulation results unveiled that the pandemic can be controlled if other control measures, such as face mask wearing in public areas and washing of hands, are combined with high level of compliance to physical distancing. Furthermore, an autonomous derivative equation for the five-dimensional deterministic was done with two control terms and constant rates for the pharmaceutical and non-pharmaceutical strategies. The Lagrangian and Hamilton were formulated to study the model optimal control existence, using Pontryagin’s Maximum Principle describing the optimal control terms. The designed objective functional reduced the intervention costs and infections. We concluded that the COVID-19 curve can be flattened through strict compliance to both pharmaceutical and non-pharmaceutical strategies. The more the compliance level to physical distance and taking of vaccine, the earlier the curve is flattened and the earlier the economy will be bounce-back.
... Transmission through asymptomatic contact also seemed highly probable (3) , a feature that was not previously seen with SARS-CoV or MERS-CoV. Clinical spectrum of SARS-CoV-2 infection ranges from flu-like illness to pneumonia with rapid progression to acute respiratory distress syndrome (ARDS) and death (1,(4)(5)(6) . The fatality rates for hospitalized COVID-19 patients varies between 0.6% to 15% (1,5,6) . ...
Full-text available
Background: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. Methods: A novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration was applied to investigate the effect of border restriction between Hong Kong and mainland China on the epidemiological characteristics of COVID-19 in Hong Kong. Isolation facilities occupancy was also studied. Results: At R0 is set to be inversely correlated with temperature of 2.2, the cumulative COVID-19 cases in Hong Kong can be reduced by 13.99% (from 29,163 to 25,084) with complete border closure. At an in-patient mortality of 1.4%, the number of deaths can be reduced from 408 to 351 (57 lives saved). However, border closure alone was insufficient to prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary. Conclusions: As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality.
... A fecal-oral transmission route cannot be dismissed, as the SARS-CoV-2 has been reported in the fecal samples of patients in the United States and in China [9] . However, a study from Germany did not identify any live, virus in stools despite detectable viral RNA, suggesting that the detectable viral RNA may be due to viral debris rather than active virus [10] . Further studies are required to confirm this finding. ...
SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)—as generated by the immune system following infection or vaccination—has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG) and inhibitory capacity in asymptomatic individuals between Jan 2021 and May 2022. These data were generated as part of a large university COVID monitoring program and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees’ saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data demonstrate that COVID vaccines achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.
There is a new public health crisis threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as it is now called, is rapidly spreading from its origin in Wuhan City of Hubei Province of China to the rest of the world. Coronaviruses are enveloped positive-sense RNA viruses that are diversely found in humans and wildlife originated in bats ranging from 60 nm to 140 nm in diameter with spike-like projections on its surface giving it a crown-like appearance under the electron microscope, hence the name coronavirus. A total of six species have been identified which are known to infect the neurological, respiratory, enteric, and hepatic systems. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 days. The symptoms are usually fever, cough, sore throat, breathlessness, fatigue, and malaise among others. The disease is mild in most people; in some (usually the elderly and those with comorbidities), it may progress to pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan dysfunction. Many people are asymptomatic. The case fatality rate is estimated to range from 2 to 3%. Treatment is essentially supportive; role of antiviral agents is yet to be established. Prevention entails home isolation of suspected cases and those with mild illnesses and strict infection control measure at hospitals that include contact and droplet precautions. The global impact of this new epidemic is yet uncertain. We conducted a literature review of publicly available information to summarize knowledge about the pathogen and the current epidemic. In this literature review, the causative agent, epidemiology, pathogenesis, diagnosis, and nurses role regarding disease, control, and prevention strategies are all reviewed. It will also provide a means to raise awareness among primary and secondary health-care providers during the current pandemic.
Zusammenfassung Hintergrund Unterscheidet sich der Rehaverlauf von akut Covid-19-Erkrankten von genesenen Covid-19-Patienten und anderen Rehapatienten? Vergleich des Verlaufs zwischen akut Covid-19-Erkrankten, genesenen Patienten und Rehapatienten ohne Covid-19. Design: Fall-Kontroll-Studie. Material und Methoden Einschluss von im Zeitraum 01.04. bis 30.06.2020 zugewiesenen Patienten mit aktiver Covid-19-Erkrankung (IG), genesenen Covid-19-Betroffenen (PCG) und einer gleichzeitig rehabilitierten, nach Alter, Geschlecht und Komorbidität gematchten Kontrollgruppe (Ko). Primärer Endpunkt war die Selbständigkeit im Alltag (FIM), weitere Endpunkte waren Lebensqualität (EQ5D-VAS), physische und mentale Gesundheit (PROMIS10) sowie Mobilität (TUG und 6MWT). Ergebnisse 101 Patienten wurden eingeschlossen: IG=15; PCG=22; Ko=64. Die Selbständigkeit und Lebensqualität bei Eintritt waren in der IG signifikant am höchsten (FIM IG 95,3 vs. PCG 78,3, vs. Ko 79,6; ANOVA p=0,029; EQ5D-VAS IG 56.1 vs. PCG 36,6 vs. Ko 51,0; ANOVA p=0,010). Im PROMIS10 sowie in der Mobilität gab es keine Unterschiede. Alle drei Gruppen verbesserten sich von Ein- zu Austritt signifikant. Die IG schnitt bei Austritt im FIM am besten ab (IG 109,7 vs. PCG 97,2 vs. Ko 93,6; ANOVA p=0,039). Die Kontrollgruppe erreichte hinsichtlich Mobilität bei Austritt die schlechtesten Resultate (TUG Ko 19,3 Sek. vs. 9,6 Sek IG und 8,3 Sek PCG). Im 6MWT zeigte die PCG das beste Resultat (471 m vs. IG 416 m und Ko 389 m; Differenz n.s.). Schlussfolgerung Alle drei Patientengruppen konnten sehr gut vom Rehaprogramm profitieren. Rehamassnahmen bringen auch für isolierte akut Covid-19-Erkrankte einen Benefit. Insbesondere genesene Covid-19-Patienten profitieren sehr von den Rehamassnahmen.
Bandar Lampung termasuk daerah dengan prevalensi Covid-19 tertinggi di Provinsi Lampung dengan total kematian sampai bulan September 2020 mencapai 15 pasien. Penyakit ini rentan menyerang remaja sekolah karena kelompok remaja menjadi komunitas yang banyak beraktifitas di luar rumah sehingga berisiko terpapar Covid-19. Remaja biasanya terinfeksi dengan status tanpa gejala sehingga berisiko menularkan. SMAN 2 Bandar lampung merupakan sekolah favorit dan diharapkan pengabdian kepada masyarakat (PKM) ini akan membentuk komunitas remaja yang bisa menjadi model pelaku protokol Covid-19. Kegiatan PKM ini bertujuan meningkatkan imunitas atau status kesehatan pada kelompok remaja target melalui edukasi untuk menerapkan protokol Covid-19 untuk membangun perilaku sehat sebagai upaya pencegahan Covid-19. Metode PKM menggunakan teknik penyuluhan serta demonstrasi video dan edukasi yang menunjukkan beberapa hal mengenai covid-19 dan pencegahannya, aturan menjaga jarak, cuci tangan dan masker yang dipresentasikan melalui daring, buku saku dan pamflet sebagai wahana edukasi berkelanjutan. Proses kegiatan yang dilaksanakan didapatkan peningkatan pengetahuan berdasarkan nilai rata-rata post-test sebesar 83, sedangkan nilai pre-test hanya sebesar 65. Diharapkan para siswa dapat mengimplikasikan pengetahuan dan pemahaman yang didapat mengenai protokol Covid-19 dan pencegahannya pada diri sendiri dan lingkungan sekitarnya.
Full-text available
In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
Researchers are racing to find out more about the epidemiology and genetic sequence of the coronavirus spreading in Asia and beyond. Researchers are racing to find out more about the epidemiology and genetic sequence of the coronavirus spreading in Asia and beyond. Medical staff transfer patients to Jin Yintan hospital in Wuhan, Hubei, China
Diagnostic detection of Wuhan coronavirus 2019 by real-time RT-PCR. Geneva: World Health Organization
  • V Corman
  • T Bleicker
  • S Brünink
Corman V, Bleicker T, Brünink S, et al. Diagnostic detection of Wuhan coronavirus 2019 by real-time RT-PCR. Geneva: World Health Organization, January 13, 2020 (https://www . who. int/ docs/ default -source/ coronaviruse/ wuhan -virus -assay -v1991527e5122341d99287a1b17c111902. pdf).
China coronavirus: Six questions scientists are asking
  • Callaway E.
  • Cyranoski D.