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Exclusive | New Coronavirus gene sequencing traceability: when is the alarm sounded
February 26, 2020 22:10 from Caixin.com
The isolation, detection and gene sequencing of the new coronavirus is the basis for understanding and judging the infectivity and harmfulness of the new coronavirus. When and how did this study start? On January 11, the update of the Wuhan Health and Health Commission ceased for several days, and the "unexplained viral pneumonia" was renamed "new coronavirus-infected pneumonia" for the first time, saying that as of 14:00 on January 10, 2020, 41 cases of newly diagnosed new coronary pneumonia
[Caixin.com] (Reporter Gao Yu Peng Yanfeng Yang Rui Feng Yuding Ma Danmeng)
Tracing back to the source, as of February 24, more than 2,660 people have died and more than 77,000 people have been diagnosed with the new coronavirus. When was this new coronavirus close to SARS discovered? The Caixin reporter conducted interviews from various sources and sorted out related papers and database data to verify the information puzzle gradually and completely emerged.
All kinds of evidence show that before the end of December last year, no fewer than 9 samples of unknown pneumonia cases were collected from various hospitals in Wuhan, and genetic sequencing showed that the pathogen was a SARS-like coronavirus. These test results were fed back to the hospital and reported to the health Health committee and disease control system. Until January 9, CCTV reported that the "Wuhan Viral Pneumonia Pathogens Preliminary Evaluation Expert Group" officially announced that the pathogen was a "new coronavirus."
The first case comes out on December 27
On December 15, 2019, a 65-year-old male delivery man from the South China Seafood Market started to have a fever. On December 18, he went to the emergency department of Wuhan Central Hospital (Nanjing Road) to see a doctor. The doctor suspected that it might be community-acquired pneumonia and admitted him to the emergency department ward of the hospital. Community-acquired pneumonia is a general term for a type of pneumonia caused by bacteria, viruses, chlamydia, and mycoplasma. The main clinical symptoms are cough, with or without sputum, and chest pain.
On December 22, the patient became worse and entered the ICU, and the doctors used various antibiotics to treat it. Professor Zhao Su, the chief physician of the Department of Respiratory Medicine of Wuhan Central Hospital, told Caixin that on December 24, a deputy chief physician of the Department of Respiratory Medicine performed bronchoscopy on the patient, and then sent the patient ’s alveolar lavage fluid sample to the first The tripartite testing agency Guangzhou Weiyuan Gene Technology Co., Ltd. conducts NGS testing, hoping to use its second-generation high-throughput gene sequencing technology (mNGS) based on metagenomics to identify pathogens. Alveolar lavage is a treatment method that removes inflammatory secretions in alveoli and improves respiratory function. For lower respiratory tract and lung diseases, the content of pathogens in alveolar lavage fluid is higher than that of pharyngeal swabs.
Weiyuan Gene is the full name of Guangzhou Weiyuan Gene Technology Co., Ltd., established in June 2018. Its job advertisement claims to focus on precision medicine in oncology and infectious etiology, and has a sequencing platform (NGS) based on second-generation high-throughput sequencing technology.
"Since BGI started to use sequencing technology, there have been many gene sequencing companies in China, large and small. Over the years, at our various medical seminars, the second-generation high-throughput gene sequencing technology has been continuously introduced, and these companies have also sent medicine Delegates went to major hospitals to preach. "Zhao Su told Caixin reporter. Huada Gene (300676.SZ) is called Shenzhen Huada Gene Co., Ltd., formerly known as Beijing Huada Gene Research Center. It was established in 1999 and has completed several parts of the International Human Genome Project, the Rice and Giant Panda Genome Project, etc. Genome research work with international advanced level. It was the largest genomics research and development institution in the world in July 2017, with the first share of gene sequencing.
Another doctor from Wuhan Union Medical College Hospital also introduced, "Once tested, 6 million base sequences, 3,000 yuan, these 3,000 yuan can find out what pathogen or virus is the pathogen, and may save lives."
Generally speaking, gene sequencing companies should feedback the test results three days later, that is, December 27, but Weiyuan Gene did not give a written report. "They just informed us by phone that they are a new coronavirus." Zhao Su said. This patient was transferred to Wuhan Tongji Hospital on December 25.
On February 21, 2020, the genetic testing information of this case was disclosed by an article on WeChat public account "Weiyuan Gene". The public article wrote that the Chinese Medical Journal (English version) published a paper on January 27, introducing the beginning and end of the discovery of the new coronavirus. Weiyuan gene participated in the early discovery of the new coronavirus.
The aforementioned paper published in the Chinese Medical Journal (English version) refers to the article "Identifying a novel coronavirus that can cause severe pneumonia in humans: a descriptive study" published on January 29. The authors are from the Chinese Academy of Medical Sciences / Beijing Union Medical College Institute of Pathogen Biology (hereinafter referred to as the Chinese Academy of Medical Sciences Pathogens), China-Japan Friendship Hospital, Hubei Provincial Center for Disease Control, Wuhan Jinyintan Hospital, Wuhan Central Hospital, Guangzhou Weiyuan Gene Technology Co., Ltd. and other units. Xu Teng, the chief technology officer of Weiyuan Gene, is the co-first author of the paper, CEO Li Yongjun and chief operating officer Wang Xiaorui are the co-authors. Li Yongjun was a bioinformatic analyst at the Institute of Pathogens, Chinese Academy of Medical Sciences.
According to the paper, the researchers collected clinical data and bronchoalveolar lavage samples from 5 patients with severe pneumonia in Wuhan Jinyintan Hospital, Hubei, and conducted pathogenic metagenomics (mNGS) analysis. As a result, in these samples, a coronavirus that had never been reported before and that had 79% similarity to the nucleotide sequence of SARS virus was found. The article shows that among the samples of these five patients, the earliest clinical sample for gene sequencing was a 65-year-old patient sample collected on December 24. He developed symptoms on December 15 and his symptoms were high fever, cough, and less sputum. He was admitted on the 18th and was admitted to the ICU on December 22. After 16 days, the fever continued and developed severe shortness of breath.
Is also highly consistent with the above information, is an article titled "Recording the experience of the first discovery of a new coronavirus" published on the WeChat public account "Small Dog" on January 28. The author claimed to work in a private company located in Huangpu, Guangzhou in the message area. The article records: "Just started working on December 26, 2019, or as usual, first glance at the automatic interpretation of mNGS pathogenic microorganisms on this day. The unexpected thing is that It was found that a sample reported a sensitive pathogen, SARS coronavirus, with dozens of sequences, and this sample only has such a meaningful pathogen. As soon as I was in my heart, I quickly checked the detailed analysis data in the background and found that the similarity was not It is very high, only about 94.5%. In order to confirm the reliability of the results, a detailed analysis was started. The analysis results of the exploratory version suggest that this pathogen is the most similar to Bat SARS like coronavirus (bat SARS coronavirus), the overall similarity is 87% It ’s about 81% similar to SARS. "
According to the author, the patient's sample was also collected on December 24. It is mentioned in the article, "The front-end reports that this patient is seriously ill and is anxious to test the results, but such a major pathogen cannot be easily reported. At noon, he held an emergency meeting with several leaders and decided to continue in-depth analysis and delay the issuance of reports. Share the data with the Chinese Academy of Medical Sciences' Pathogen Institute for analysis ". The Institute of Pathogens of the Chinese Academy of Medical Sciences is the Institute of Pathogens of the Chinese Academy of Medical Sciences, which was one of the authors of the Chinese Medical Journal (English Version) and Li Yuanjun, the CEO of Weiyuan Gene, and is directly under the president of the Chinese Academy of Medical Sciences. Academician Wang Chen, vice president of the Chinese Academy of Engineering.
On December 27, the laboratory assembled a nearly complete viral genome sequence, and the data was also shared with the Institute of Pathology, Chinese Academy of Medical Sciences. "It can basically be confirmed that there is indeed a new virus similar to Bat SARS like coronavirus in the sample of this patient." The article wrote, "The information obtained at the time was that this patient had returned to his hometown and did not rule out contact with bats. Realized the potential of the problem Severity, the laboratory was completely cleaned and disinfected, the samples were harmlessly destroyed, and the relevant personnel of the experimental operation conducted relevant monitoring. I had communicated with the doctor before noon, and the patient was also quarantined. "
"It should be the first time we discovered this new coronavirus." The "Small Dog" article also gave a screenshot of the GISAID database. "From the data submitted on the GISAID database website, the earliest sample collection time is also ours."
GISAID is a global influenza virus shared data platform, and scientific researchers can upload their extracted viral gene sequences after registration. Each strain will have a unique number, and the collection time, date of submission, and laboratory submission will be recorded. A Caixin reporter checked and found that the earliest new coronavirus gene sequence on GISAIDS was collected on December 24, 2019, and uploaded by the Institute of Pathology, Chinese Academy of Medical Sciences on January 11, according to the sample collection time. The comparison number, name, etc. can be found, this is the sample sequence of their company involved in the detection marked in the screenshot of the article "Small Dog".
The article also mentioned that the company's leaders communicated with the hospital and the CDC (department) on December 27 and 28, and even went to Wuhan to personally report all the analysis results to the leaders of the hospital and CDC on the 29 and 30. Including all our analysis results and the analysis results of the Institute of Pathology of the Academy of Medical Sciences. Everything is under intense, confidential and strict investigation (at this time, the hospital and the disease control people already know that there are many similar patients, we communicated the test results Emergency treatment has been started) ".
The owner of the above-mentioned sample known to have completed the earliest gene sequencing was later killed in Jinyintan Hospital. This case has detected the new virus research results on December 27, and did not play any role at that time.
"SARS Coronavirus" detonates social media
In fact, in addition to the earliest known case, at the end of December 2019, two samples of patients with "unexplained pneumonia" in Wuhan Central Hospital were sent to different institutions for gene sequencing. The test results of these two samples have had a significant impact on the publicity of the epidemic in different ways.
On December 27, a 41-year-old man named Chen went to the Nanjing Road Campus of Wuhan Central Hospital. "He is an accountant and lives in Wuchang. He has never been to the South China Seafood Market in Hankou. He probably started fever on December 16 with no obvious incentives. The highest body temperature was 39.5 ° C, accompanied by palpitations, chest tightness, difficulty breathing after exercise, and physical strength. Significant decline, firstly on December 22 at the First People's Hospital of Jiangxia District, there was no improvement. "Zhao Su revealed to Caixin reporter," He is an acquaintance of a doctor in our hospital, and he was transferred to our hospital on the 27th, which is also the emergency department. Received. "On the evening of December 27, the patient took a bronchoscope in the ICU of the hospital's respiratory department. This time the sample was sent to another Beijing Boao Medical Laboratory Co., Ltd., which is engaged in NGS testing.
On December 30, the Beijing Boao Medical Laboratory reported the patient ’s report to the doctor. The test result was directly “SARS coronavirus” (SARS coronavirus).
The test report of the Beijing Boao Medical Laboratory obtained by Caixin reporter showed that high-confidence positive indicators of SARS coronavirus and Pseudomonas aeruginosa were detected in the patient ’s sample. Among them, the explanation for SARS coronavirus is: a single-stranded positive-strand RNA virus, the virus is spread by close-range droplet transmission or contact with the respiratory secretions of patients, which can cause a clearly contagious and can involve multiple organs Systemic special pneumonia, also known as atypical pneumonia.
"Their gene bank is not complete, and may not have been reviewed, so they made a small mistake. In fact, it is not the same thing as SARS, it is a new coronavirus." A gene sequencing expert revealed to Caixin reporters.
However, it was this test report that made a small mistake, but it directly attracted the attention of Wuhan doctors. The social media blew the whistle to the public and saved a considerable number of lives.
On December 30, the test report of Beijing Boao Medical Laboratory appeared on the WeChat of the doctor of Wuhan Central Hospital. At 17:48 in the evening, Li Wenliang, an ophthalmologist at Wuhan City Central Hospital, released a message to his classmates: "7 cases of SARS were diagnosed in the South China Fruit and Seafood Market and were isolated in the emergency department of our hospital"; 19:39, Wuhan Red Cross Liu Wen, a neurologist at the hospital, released a message on the WeChat group "Xiehe Red Society" saying: "Just after the second hospital (ie Wuhan Central Hospital), a case of coronary infectious viral pneumonia was diagnosed in the Houhu district, maybe it will be isolated around South China." "SARS has been basically confirmed, nurses and sisters don't go out and shake"; at 20:48, Xie Linka, a doctor at the Cancer Center of Wuhan Union Medical College Hospital, published a message in the WeChat Group of the Cancer Center. Many people have unexplained pneumonia (similar to SARS). Today, our hospital has admitted many cases of pneumonia in the South China Seafood Market. Everyone should pay attention to wearing masks and ventilation "-these three doctors have been advised by the police since then.
On the same day, the author of the "Small Dog" article in Huangpu, Guangzhou, also learned the above news. He wrote: "By December 30, I heard the news that there were quite a few patients with similar symptoms, and the nerves suddenly disappeared. It's tense. In particular, around the afternoon of the 30th, a friend may have detected the same virus in the sample of another patient, but they directly sent a report of the detection of SARS coronavirus and immediately detonated the message. Now ... Friends and merchants shared the sequence for our analysis. I analyzed it and found that it is indeed the same virus! The first idea in the subconscious mind is 'This virus is infectious'! "
Li Wenliang and others lifted the lid, allowing the genetic company to sequence the story of this line, which intersects with another story of clinician warning. While the doctors at the Wuhan Central Hospital are ineffective for routine treatment of viral pneumonia patients, and hope to find answers through gene sequencing companies, Zhang Jixian, director of the Department of Respiratory and Intensive Medicine of Hubei Xinhua Hospital adjacent to the South China Seafood Market Four consecutive cases of unexplained pneumonia were seen on the day. On December 27, Zhang Jixian reported four cases of "unexplained viral pneumonia" to the hospital, and the hospital reported to the Jianghan District Disease Control Center.
On December 28-29, Xinhua Hospital admitted three patients from the South China Seafood Market who had similar symptoms of viral pneumonia. According to later reports such as "Wuhan Evening News", at 1 pm on December 29, Xia Wenguang, the deputy director of Xinhua Hospital, summoned ten experts to discuss the seven cases. The experts agreed that the situation was unusual, and Xia Wenguang directly sent to the provincial and municipal health levels. Report from the CDC. Also reported on the same day was the Public Health Department of Wuhan Central Hospital. On the afternoon of the same day, Hubei Province, Wuhan Municipal Health and Health Commission's CDC notified the provincial, municipal, and district three-level disease control centers, Xinhua Hospital, and Central Hospital Houhu District to treat many unknown pneumonia patients with history of seafood market exposure. Start the emergency handling workflow. Hubei Disease Control Center, Wuhan
