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

Shiloh

Editor, Senior Moderator
Source: https://www.nejm.org/doi/full/10.1056/NEJMc2001468?query=featured_home

January 30, 2020
DOI: 10.1056/NEJMc2001468
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 its identification 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 of Asia in which transmission appears to have occurred during the incubation period in the index patient...
 
It is my understanding that all journals have declared 2019-nCov materials to be OPEN SOURCE. :applause:


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.[SUP]1[/SUP] Since its identification 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 of 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.

Figure 1.
nejmc2001468_f1.jpeg
Timeline of Exposure to Index Patient with Asymptomatic 2019-CoV Infection in Germany.

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 Jan. 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).

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.[SUP]2[/SUP] Follow-up qRT-PCR assay revealed a high viral load of 10[SUP]8[/SUP] 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 of 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.[SUP]3[/SUP]

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.

Camilla Rothe, M.D.
Mirjam Schunk, M.D.
Peter Sothmann, M.D.
Gisela Bretzel, M.D.
Guenter Froeschl, M.D.
Claudia Wallrauch, M.D.
Thorbj?rn Zimmer, M.D.
Verena Thiel, M.D.
Christian Janke, M.D.
University Hospital LMU Munich, Munich, Germany
rothe@lrz.uni-muenchen.de

Wolfgang Guggemos, M.D.
Michael Seilmaier, M.D.
Klinikum M?nchen-Schwabing, Munich, Germany

Christian Drosten, M.D.
Charit? Universit?tsmedizin Berlin, Berlin, Germany

Patrick Vollmar, M.D.
Katrin Zwirglmaier, Ph.D.
Sabine Zange, M.D.
Roman W?lfel, 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 available with the full text of this letter at NEJM.org.

This letter was published on January 30, 2020, at NEJM.org.
 
[h=1]Study claiming new coronavirus can be transmitted by people without symptoms was flawed[/h]
By Kai Kupferschmidt
Feb. 3, 2020 , 5:30 PM
A paper published on 30 January in The New England Journal of Medicine (NEJM) about the first four people in Germany infected with a novel coronavirus made many headlines because it seemed to confirm what public health experts feared: that someone who has no symptoms from infection with the virus, named 2019-nCoV, can still transmit it to others. That might make controlling the virus much harder.

Chinese researchers had previously suggested asymptomatic people might transmit the virus but had not presented clear-cut evidence. “There’s no doubt after reading [the NEJM] paper that asymptomatic transmission is occurring,” Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, told journalists. “This study lays the question to rest.”

But now, it turns out that information was wrong. The Robert Koch Institute (RKI), the German government’s public health agency, has written a letter to NEJM....:tiphat:https://www.sciencemag.org/news/2020/02/paper-non-symptomatic-patient-transmitting-coronavirus-wrong
 
Thanks for posting the update, Treyfish. It seems that the original authors of NEJM letter relied on the opinions of the Bavarian patients to assess the status of their team member who returned to China. The Robert Koch Institute made the effort to actually contact the person in China and she said she was exhibiting symptoms before returning to China, undermining any claim of asymptomatic transmission of n-CoV.

It is clear that human-to-human transmission is occurring in this cluster in Germany including different generations in the same family. We will have to wait for more information from the public health official there to determine if any of these family infections can be assigned to asymptomatic transmission.
 
I am not sure that many people would feel that tired and muscle pain was a symptom. This is exactly the sort of feelings you get when you have been exercising, or working hard etc.. How could anyone tell the difference? Could you call them symptoms if you were not aware you were ill?

https://www.sciencemag.org/news/2020...onavirus-wrong "According to people familiar with the call, she felt tired, suffered from muscle pain, and took paracetamol, a fever-lowering medication. (An RKI spokesperson would only confirm to Science that the woman had symptoms.)"
 
Last edited:
I agree. General tiredness and a muscle ache is not a recognizable symptom of anything except being alive.

Common sense would tell you she was functionally asymptomatic.

They could re-title the paper to Transmission of 2019-nCoV Infection from an Mostly Asymptomatic Contact in Germany
 
I have been reviewing the Chinese press conferences from the discussion thread. There are numerous mentions of cases where asymptomatic cases have passed infection onwards.

Here is a summary of such mentions. I am sure I have missed some reports, but think that the experience in China (outlined below) is fairly conclusive. There are asymptomatic infections who can pass infection onwards.


Expert: New coronaviruses are infectious when they do not have any typical symptoms during the incubation period
Published: 2020-01-26 14:35:08 | Source: Xinhua | Author: Huang Xiao Wangbing Yang
More News Enter News Center

Xinhua News Agency, Hangzhou, January 26th, reporters learned from Sheng Jifang, director of the Department of Infectious Diseases of Zhejiang University First Hospital, deputy director of the State Key Laboratory of Infectious Diseases Diagnosis and Treatment, and member of the pneumonia expert group for the diagnosis and treatment of new coronavirus infection in Zhejiang Province. Case studies of pneumonia associated with a new coronavirus infection have been contagious when there were no typical symptoms during the incubation period.

'We encountered a patient who came to Hangzhou from Wuhan to attend a conference. When he arrived in Hangzhou, he did not have any symptoms. He did not have the typical symptoms of cough and fever. But it didn't take long before several colleagues he had contacted were infected Symptoms appeared one after another. But at this time, he still did not have the disease himself. After returning to Wuhan at the end of the meeting, he did not get the disease after another two days. 'Sheng Jifang introduced.

[url]http://news.china.com.cn/2020-01/26/...t_75650029.htm[/URL]


Source: http://news.workercn.cn/32843/202001...13444934.shtml

Authoritative medical experts respond to the seven focuses of popular science
2020-01-27 21:34:43 Xinhuanet

Snippet

专家 Many experts have confirmed that the new coronavirus is contagious during the incubation period without any typical symptoms. Cao Wei, deputy director of the Department of Infectious Diseases, Peking Union Medical College Hospital, believes that from the case spread outside Hubei Province, the mortality rate of pneumonia caused by the new coronavirus infection is lower than that of SARS, with a large proportion of mild patients. Since there are no typical symptoms during the incubation period and it is contagious, it brings certain difficulties to prevention and control.

兰 Li Lanjuan, a member of the high-level expert group of the National Health and Health Committee and an academician of the Chinese Academy of Engineering, also said that the new coronavirus was found to be likely to be transmitted to other people during the incubation period. "So within 14 days of exposure to the source, medical observation and relative isolation are required."


January 28th, 2020, 02:10 AM
There are 100,000 infected people? How to prevent "contact transmission"? National Health Commission response

Published: 2020-01-28 14:35:34 | Source: BEIJING, micro-channel public number | Author: Zhang Nepal, etc.

Snippet

How to prevent and treat asymptomatic patients?
-Asymptomatic infection makes prevention and control difficult and complicated
Li Xingwang, Chief Expert of Infectious Disease Diagnosis and Research Center of Beijing Ditan Hospital:
We have observed that there may be asymptomatic infections. Although there are no symptoms, the nucleic acid test is positive. There are also some patients with such symptoms, such as fever is not obvious, occasional dry cough or fatigue, these patients are also found after we actively search and increase the detection ability. Such patients, from the perspective of the law of infectious diseases, also have a certain spreading power, which brings certain difficulties and complexity to our prevention and control work.
Now more asymptomatic infections are found among close contacts. These close contacts are now undergoing medical observation according to current requirements. They may not go to public places for free activities, or more. Isolation at home ensures that we have control over the source of infection.
(Zhang Ni, Tong Feng, Lang Lang, Zhang Xiaoyu)

http://news.china.com.cn/2020-01/28/...t_75654176.htm

Wuhan Pneumonia / Suspected as "asymptomatic infection"! She returned home for 19 days without any symptoms

January 29, 2020 Edited by Chen Yiwen

The pneumonia epidemic in Wuhan spread. One woman was suspected of being "asymptomatic" and infected five relatives and friends. (Photo: Weibo of Wuhan Central Hospital)

The pneumonia epidemic in Wuhan is spreading. Experts continue to study the way of spreading and have confirmed that even "contact" may allow the virus to spread. A woman named Lu returned to her hometown in Henan from Wuhan on the 10th to celebrate the New Year. No illness has been reported for 19 days, but her 5 relatives and friends have been diagnosed one after another! It is suspected that Lu Nu is an "asymptomatic infection". The local health and health committee has asked experts to study the infection process in this case and to test Lu Nu for a new coronavirus.

According to comprehensive land media reports, the former (27th) Anyang City, Henan Province released four newly confirmed cases, of which three were brother-sister relationships. Lu Man, 45, developed fever and respiratory symptoms on the 23rd and was diagnosed on the 26th. The second case was a 47-year-old Lu woman. She was Lu's brother. She had a fever and sore throat at the clinic on the 14th. The symptoms had improved, but her condition became worse on the 24th. A diagnosis was made on the 26th.

The third case was the 48-year-old Lu Nu, who was also the sister of the first case. She had contact history with a woman who returned to the Chinese New Year (sister-in-law). She developed fever and respiratory symptoms on the 25th and was diagnosed on the 26th. The fourth case was a 42-year-old aunt named Lu, who was diagnosed on the 27th after symptoms appeared on the 25th. The last case was Lu Nan's 42-year-old wife Zhou Nu, who also developed symptoms on the 26th and was diagnosed on the 27th.

None of the five confirmed cases had a history of travel and residence in Wuhan, and only Lu's daughter had returned home from Wuhan to spend the New Year, but she did not develop the disease and caused outside concern that she had returned home for 19 days. "Should I have passed the quarantine period, why hasn't she developed the disease herself? "Many people think that if she is" asymptomatic ", how can the people around her determine whether she is a close contact?

Yesterday (28th), the Anyang City Health and Health Committee said that it was not yet certain that the five confirmed cases were all infected by Lu Nuo, who was returned to Wuhan. So far, experts have been consulted for research; as for those who are suspected to be "asymptomatic" Lu Lu, who has been tested for viruses, has not yet announced the results.

https://www.ctwant.com/article/34642


Source: http://news.cjn.cn/sywh/202001/t3550022.htm
6 people with no obvious symptoms in the elderly? Expert: Viruses invade different people and behave differently
2020-01-31 22:31 Source: Yangtze River Network
Adjust font
Yangtze River Network January 31 (Reporter Liu Ruiche Correspondent Feng Xia) The virus is evolving and has now "no fever, no cough". The asymptomatic elderly were passed on to six people in the family. Recently, viral mutations circulating on the Internet have been worrying. On January 31, Changjiang Daily-Changjiang.com reporters learned from clinical front-line and virology experts that there is no evidence of new types of coronavirus mutations. The virus behaves differently in different people, and indeed there are patients who carry the virus but have no obvious symptoms.

January 31st, 2020, 12:17 PM
Translation Google


Outbreak of new coronavirus pneumonia

At the turning point of the Wuhan epidemic: Will asymptomatic new crown virus infected people break through the prevention and control system?

First Financial 2020-01-31 10:14:20

Zhang Wenhong

How does asymptomatic infection affect the development of the epidemic?

Recently, the outbreak of new coronavirus pneumonia in Wuhan has attracted worldwide attention, and the bombardment of information on social media has affected the hearts of people across the country. In order to help everyone understand the dynamic changes of the epidemic, the WeChat public account “Huashan Infection” of Huashan Hospital's Infection Department affiliated to Fudan University updates the relevant data of the epidemic every day, and invites Professor Zhang Wenhong, director of the Department of Infectious Diseases of Huashan Hospital, on the trend, hot issues and related issues Cautions, specifically for Q & A interpretation.

Professor Zhang Wenhong is also the leader of the Shanghai New Coronavirus Pneumonia Medical Treatment Expert Group.

Daily battle report: Asymptomatic infections sneak into our prevention and control system?
...
National Health Commission: Among the close contacts of sporadic cases, we have observed that there may be asymptomatic infections. Although there are no symptoms, the nucleic acid test is positive.

Other patients have such symptoms, such as fever not being obvious, occasional dry cough or fatigue. Such patients, from the perspective of the law of infectious diseases, also have a certain spreading power, which brings certain difficulties and complexity to our prevention and control work. As the current technology for screening for infectious agents is mainly symptomatic, or even only for patients with pneumonia, asymptomatic patients may be missed, and then spread in a wide range in communities and shopping malls, and the second generation appears. Three generations and even N generations.

Reports of asymptomatic infection are gradually appearing everywhere, causing public concern. Asymptomatic means that these infected people lack the fever and respiratory symptoms of typical new coronavirus infection, but the nucleic acid test is positive. It is feared that the emergence of asymptomatic infection will make the epidemic more difficult to control because there may be more cases of infection after contact with any symptomatic person, which also makes some of our previous prevention and control screening standards meaningless. So what are the effects of asymptomatic infections on the development of the epidemic?

We answer from the following aspects!

Does the so-called neocrown virus asymptomatic infection actually exist?

First of all, it is entirely possible that such so-called asymptomatic infections may occur. Based on the analysis of current clinical data, compared with SARS and MERS, the proportion of mild patients is higher, and mild and asymptomatic patients often have there is no absolute dividing line . So asymptomatic can also be very mild, making it difficult for patients to detect. From the current epidemiological data, at least from the perspective of family clustered cases, the source cases have preceded the onset. The so-called source cases (also known as academically indicated cases) infect people when they are asymptomatic. This is not called asymptomatic infection. At present, those who are more asymptomatic are the Henan Anyang family who recently reported on the Internet. The so-called indicated cases have been asymptomatic. In fact, this situation is not good enough to say that it must be an asymptomatic case. It is also possible that the case had very mild symptoms without knowing it, and soon entered the recovery period. Whether it is asymptomatic requires a series of virological and serological studies in people who do not develop disease in close contacts to draw conclusions.

A classic case in history tells you what an asymptomatic person is

Is it possible that an asymptomatic person is a persistent asymptomatic person ? With the addition of two words, the epidemiological significance is completely different. Persistent infection indicates that the infected person is always a source of infection, and he can constantly cause contact infection. A persistent asymptomatic infection called "typhoid Mary" appeared in New York, USA in the early last century. This family cook, named Mary, was infected with typhoid bacteria (a type of bacteria that causes typhoid fever) but did not have symptoms of typhoid, and accidentally infected 51 people, three of whom died. She was forcibly quarantined twice by New York public health authorities for a total of 30 years. So is there a similar situation for the new coronavirus in 2019? We have to say that this is almost impossible . Although the data on the longest time of nucleic acid positivity in known patients is not known at present, from previous respiratory viruses such as influenza, parainfluenza, rhinovirus, metapneumovirus, and adenovirus to the six coronaviruses previously discovered none of them had experienced persistent asymptomatic infections .

Can asymptomatic cases become super-spreaders and lead to an out-of-control situation?

Everyone is more worried about whether there is no symptoms, but they are a super communicator. The so-called super communicator , when we were SARS, we called the drug king, that is, a patient infected multiple patients at the same time due to various reasons. In the news, we called these people "big V". Why is it less likely? Coronavirus, as a virus that is mainly transmitted through the respiratory tract, spreads the virus to surrounding susceptible people by means of droplets produced by patients such as coughing and sneezing. And if a person is not infected with respiratory symptoms, it is difficult to produce an effective route of transmission . In an inappropriate analogy, you can hardly ask a network "big V" to remain unknown, but at the same time be able to broadcast information to a large number of people at the same time. Secondly, from the experience of previous SARS, the poison king at that time was mostly transmitted to many close contacts due to severe cases with very obvious respiratory symptoms (such as close family care of patients, medical staff, or lack of the risk of isolation in emergency settings such as emergency rooms to other patients in close proximity), or due to medical staff's ineffective protection of themselves during medical procedures that produce aerosols such as intubation, and the risk of asymptomatic infection It almost doesn't exist, so don't worry too much.

Proportion of asymptomatic infection requires retrospective serological study

So how many people in the crowd are asymptomatic? For the 2019 new coronavirus, further research is needed. In general, to know how many people in a population have been infected with an infectious disease, it is more meaningful to detect antibodies than nucleic acids. Because we mentioned earlier that nucleic acids will only appear in the body for a period of time. As the virus is immune cleared by the body, nucleic acids will not be detected. The absence of a nucleic acid indicates that it is not contagious . However, specific antibodies are produced in the body (this process usually takes 1-4 weeks) and persists. In this way, when we want to know how many people in the population have ever been infected with a virus, the most effective method is to detect the proportion of people who have developed antibodies in the blood . This value can be used to estimate how many people have been infected. This number is then subtracted from the number of clearly infected people (including the sum of recovered and dead people), and the rest is the proportion of asymptomatic people. At present, new cases are constantly appearing across the country, so the proportion of asymptomatic infections cannot be calculated well , but if it is possible to detect the first-generation cases later (for example, the entire South China in 2019 The seafood market has people who have been exposed to antibodies), and it may be possible to understand the proportion of asymptomatic infections.

Min public as long as the firm implementation of the current control measures sufficient to prevent and control the threat of asymptomatic infected persons

The previous questions are clear, and how to prevent and control asymptomatic infection becomes clearer. First of all, we still repeatedly emphasize good personal hygiene , proper hand washing (soap and running water) and correct cough (using paper towels or elbows). Second, during high epidemics, avoid going to crowded places and minimize the chance of close contact with strangers. If it is absolutely necessary, you should wear a mask . Finally, during the high epidemic period, for patients who cannot completely rule out infection with the new coronavirus without fever and respiratory symptoms, but who have been treated for other reasons (especially with an epidemiological history), avoid unnecessary aerosols as much as possible for operations such as sputum suction and intubation, if you have to do so, you should find a way to conduct nucleic acid screening or protect medical personnel according to the third level protection.

For those with asymptomatic infections, to sum up, there is the possibility of "asymptomatic infections", but their chances of becoming a continuous source of infection and super spreaders are very small, and the proportion of asymptomatic infections needs further research. Existing Hygiene habits and sound medical procedures can help to prevent infection by these asymptomatic people.

Professor Lu Shan, Executive Editor of Emerging Mirobes and Infections, Massachusetts International Medical College, is a friend of the author. He is a Chinese American and a more objective scientist. His latest opinion is to lock himself in this way. , Inactivity has a huge effect on virus control, and the subsequent epidemic situation is likely to change, or even disappear completely over a period of time, is possible.

In short, the key to current prevention and control is to resolutely implement the two-week control and resolutely shut down potential asymptomatic carriers. According to Professor Lu Shan's opinion, this is already the case. We might as well be more optimistic. Now the people of the whole country do not go out at home. They do not go to work during the Spring Festival. They are also delayed to work. Compared with the infection during normal work, Very lucky.

Wen / Wang Xinyu (Deputy Chief Physician, Department of Infectious Diseases, Huashan Hospital) Zhang Wenhong (Leader of Shanghai Medical Treatment Experts Group, Director of Infectious Diseases Department of Huashan Hospital)

(This article is reproduced from the "Huashan Infection" public account after authorization, and the copyright belongs to the Department of Infectious Diseases, Huashan Hospital, Fudan University.)

Editor-in-chief: Yunhui Yun

https://www.yicai.com/news/100484436.html
 
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