(Jennifer’s note: The following is the English translation mainly done by google translate of a report on a Chinese website at https://web.archive.org/web/20200226154223/http://china.caixin.com/2020-02-26/101520972.html)
Caixin.com (Reporter Gao Yu, Peng Yanfeng, Yang Rui, Feng Yuding, Ma Danmeng) Tracing to the source, as of February 24, more than 2660 people have died and more than 77,000 people have been diagnosed with the novel coronavirus, a novel coronavirus similar to SARS. When was it found? Caixin reporters conducted interviews from various sources and sorted out relevant papers and database materials. By piecing together all sorts of information, the full picture is gradually emerging.
All kinds of evidence show that before the end of December last year, no less than nine samples of unknown pneumonia cases were collected from hospitals in Wuhan. Gene sequencing showed that the pathogen was a SARS-like coronavirus. These test results were reported back to the hospital and reported to the Health Commission and Disease Control System. Until January 9th, CCTV reported that the “Wuhan Viral Pneumonia Pathogen Testing Results Preliminary Evaluation Expert Group” officially announced the pathogen as “novel coronavirus”.
The Test Result of the First Case Came Out as Early as Dec. 27
On December 15, 2019, a 65-year-old male delivery man in the South China Seafood Market started having a fever. On December 18, he came to the emergency department of the Wuhan Central Hospital (Nanjing Road District) 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 generic term for pneumonia caused by a variety of microorganisms such as bacteria, viruses, chlamydia, and mycoplasma. The main clinical symptoms are cough, with or without sputum, and chest pain.
On December 22, the patient became iller and entered the ICU. Doctors used various antibiotics to treat him, but without any good result. Professor Zhao Su, the chief physician of the Department of Respiratory Medicine of Wuhan Central Hospital, told Caixin reporter that on December 24, a deputy chief physician of Respiratory Medicine took a bronchoscopy sample from the patient, and then sent the patient’s alveolar lavage fluid sample to the first 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 find pathogens. Alveolar lavage is a treatment that removes inflammatory secretions in the 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 throat swabs.
Weiyuan Gene is the full name of Guangzhou Weiyuan Gene Technology Co., Ltd., established in June 2018. Its job advertisement states that it focuses on precision medicine in oncology and infectious etiology, and has a sequencing platform (NGS) based on second-generation high-throughput sequencing technology.
“Since the start of BGI’s sequencing technology, many gene sequencing companies have appeared in China. In recent years, at our various medical seminars, the second-generation high-throughput gene sequencing technology has been continuously introduced. These companies have also sent medicines. Delegates went to major hospitals to preach. “Zhao Su told Caixin reporter. BGI (300676.SZ) is called Shenzhen BGI Gene Co., Ltd., formerly known as Beijing BGI Gene Research Center, and was established in 1999. It has successively completed a number of international human genome projects in China, rice and the giant panda genome project, with genomic research with international advanced level. In July 2017, it was listed on the GEM under the title of “The First Gene Sequencing Unit” and is the world’s largest genomics R & D institution.
Another doctor from Wuhan Union Medical College Hospital also introduced, “One test, with 6 million base sequences, costs 3,000 yuan. If with 3000 yuan’s cost, we can find out what virus or bacteria the pathogen is, it may save lives.”
Generally speaking, the gene sequencing company should feedback the test results three days later, that is, December 27, but Weiyuan Gene did not give a written report. “They just called us and said it was a new coronavirus.” Zhao Su said. At this time, the patient was transferred to Wuhan Tongji Hospital on December 25.
On February 21, 2020, the genetic test information of this case was disclosed by an article of WeChat account “Wei Yuan Gene”. The official article wrote that the Chinese Journal of Medical Sciences (English version) published a paper on January 27, introducing the discovery of new coronaviruses, and “Wei Yuan Gene” involved in the early discovery of new coronaviruses.
The aforementioned paper published in Chinese Medical Journal (English version) refers to the article “Identifying a New Coronavirus that Causes Severe Pneumonia in Humans: A Descriptive Study” published on January 29. The authors are from the Institute of Pathogen Biology of the Chinese Academy of Medical Sciences / Peking Union Medical College (hereinafter referred to as the Institute of Pathogens of the Chinese Academy of Medical Sciences), 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, and CEO Yongjun Li and chief operating officer Wang Xiaorui are the authors. Li Yongjun was a former bioinformatics 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 five patients with severe pneumonia at Jinyintan Hospital of Wuhan, Hubei Province, and performed pathogenic metagenomics (mNGS) analysis. As a result, a coronavirus with 79% similarity to the nucleotide sequence of the SARS virus had never been reported in these samples. The article shows that among the samples of these five patients, the earliest clinical sample for genetic sequencing was a 65-year-old patient sample collected on December 24. He developed symptoms on December 15 with symptoms of high fever, cough, and low sputum. He was admitted on the 18th and admitted to the ICU on December 22. After 16 days, she continued to have a high fever and developed severe shortness of breath.
Agreeing with the above information is also an article entitled “Recording the First Discovery of a New Coronavirus” published by WeChat account “Hill Dog” on January 28. The author claimed to work in a private enterprise located in Huangpu, Guangzhou in the message area. The article records: “I just went to work on December 26, 2019, and I would like to take a look at the results of the automatic interpretation of mNGS pathogenic microorganisms as usual. As a surprise, It was found that one sample reported a sensitive pathogen, SARS coronavirus, with dozens of sequences, and this sample only had such a meaningful pathogen. I was anxious, and 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 exploration version suggest that this pathogen is most similar to Bat SARS like coronavirus, with an overall similarity of 87% The similarity with SARS is about 81%. ”
According to the author, the sample collection time for this patient was December 24th. The article mentioned, “The front-end feedback is that this patient is seriously ill and is anxious to test the results, but such a major pathogen cannot be reported easily. At noon, I had an emergency meeting with several leaders and decided to continue in-depth analysis and delay the release of reports. Share the data with the Chinese Academy of Medical Sciences for analysis. ” The Institute of Pathogens of the Chinese Academy of Medical Sciences is one of the authors of the above-mentioned “Chinese Medical Journal (English Version)” thesis and Li Yuanjun, CEO of Weiyuan Gene, previously served as the Institute of Pathogens of the Chinese Academy of Medical Sciences, directly under the director 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 Pathogens, Chinese Academy of Medical Sciences. “It can basically be confirmed that this patient’s sample does indeed contain a new virus similar to Bat SARS like coronavirus.” 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 relevant personnel of the experimental operation conducted relevant monitoring. The doctor had been communicated before noon, and the patient was also isolated. ”
“It should be that we discovered this new coronavirus for the first time.” The article “Little Dog” also gave a screenshot of the GISAID database. “From the data submitted on the GISAID database website, it is also us that collected the earliest samples.”
GISAID is a global influenza virus sharing data platform. After registration, researchers can upload the virus gene sequences they extracted. Each strain will have a unique number, and the time of collection, submission date, submission laboratory, etc. will also be recorded. Caixin reporters found that according to the time of sample collection, the earliest sequence of a new coronavirus gene on GISAIDS was collected on December 24, 2019, and uploaded by the Institute of Pathogens of the Chinese Academy of Medical Sciences on January 11. It can be found by comparing the number, name, etc. This is the sample sequence of their company participating in the test marked in the screenshot of the article “Little Dog”.
The article also mentioned that on December 27th and 28th, the company’s leaders communicated with the hospital and the disease control (department) by phone. On the 29th and 30th, they even went to Wuhan to personally report and exchange all the analysis results with the leaders of the hospital and disease control center. Including all our analysis results and the analysis results of the Institute of Pathogens of the Academy of Medical Sciences. Everything is under intense, confidential, and strict investigation (at this time, the hospital and the disease control person already knew that there were many similar patients. After we communicated the test results, emergency response has begun). ”
The above-mentioned sample owner who completed the earliest genetic sequencing was later killed at Jinyintan Hospital. The research results of the new virus were detected 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 “unknown cause of pneumonia” from Wuhan Central Hospital were sent to different institutions for gene sequencing. The test results of the two cases had a significant impact on the disclosure of the epidemic in different ways.
On December 27, a 41-year-old man named Chen went to the Nanjing Road Hospital of Wuhan Central Hospital for treatment. “He is an accountant and lives in Wuchang. He has never been to the South China Seafood Market in Hankou. He started to have a fever on December 16 without any obvious cause. The maximum body temperature was 39.5 ° C, accompanied by palpitations, chest tightness, difficulty breathing after exercise, and physical strength. Significant decline, first seeing the doctor at Jiangxia District First People’s Hospital on December 22, did not improve. “Zhao Su told Caixin reporter,” He is an acquaintance of a doctor in our hospital, transferred to our hospital on the 27th, also an emergency department Closed. “On the evening of December 27, the patient took a bronchoscope sample in the ICU of the hospital’s respiratory department, and this time the sample was sent to another Beijing Boao Medical Laboratory Co., Ltd., which was engaged in NGS testing.
On December 30, Beijing Boao Medical Laboratory reported the patient’s report to the doctor, and the test result was “SARS coronavirus”.
The Beijing Boao Medical Laboratory’s test report obtained by reporter Cai Caixin showed that high-confidence positive indicators of SARS coronavirus and Pseudomonas aeruginosa were detected in the patient’s sample. The explanation of SARS coronavirus is: a single-stranded positive-strand RNA virus, which spreads by close droplets or contacts the respiratory secretions of patients, which can cause a significant infectivity and can accumulate multiple organs Systemic pneumonia, also known as atypical pneumonia.
“Their gene bank is not complete enough, or it may not have been reviewed, so they made a small mistake. In fact, it is not the same thing as SARS, or a new type of coronavirus.” A genetic sequencing expert told Caixin reporter.
However, it is this test report that made a small mistake, which directly caught the attention of doctors in Wuhan, sounded the public whistle through social media, and saved a considerable number of people’s lives to a certain extent.
On December 30th, the test report of Beijing Boao Medical Laboratory appeared in the WeChat of the doctor in Wuhan Central Hospital. At 17:48 on the evening of the same day, Li Wenliang, an ophthalmologist of Wuhan Central Hospital, released a message among the classmates: “7 cases of SARS were confirmed in the South China Fruit and Seafood Market, and they were isolated in the emergency department of our hospital.” At 19:39, the Wuhan Red Cross Hospital neurologist Liu Wen published a message in his work WeChat group “Xiehe Honghui Shennei”, saying: “Just a case of coronal infectious virus pneumonia was confirmed in Houhu District of the Second Hospital (that is, Wuhan Central Hospital). Maybe it will be isolated in southern China.” “SARS has been basically determined, nurses and sisters should not go out to shake.” At 20:48, Xie Linka, a doctor at the Cancer Center of Wuhan Union Medical College, posted a message on the WeChat group of the Cancer Center. “Don’t go to the South China Seafood Market in the near future. It is happening now. With many people suffering from unexplained pneumonia (similar to SARS), today our hospital has treated several cases of pneumonia patients in the South China Seafood Market. Everyone should pay attention to wearing masks and ventilation “-all three doctors have been cautioned by the police since then.
On the same day, the author of the “Little Dog” in Huangpu, Guangzhou, was also informed of the above news, and he wrote: “By December 30th, I heard that there were still many patients with similar symptoms, and the nerves broke down again. It ’s tense. Especially, it may be the afternoon of the 30th. A friend may have detected the same virus in the sample of another patient, but they sent a report that the SARS coronavirus was detected, and the news was detonated instantly. Now … the friends shared the sequence for us to analyze. I analyzed it and it was indeed the same virus! The first idea in the subconscious was ‘this virus is contagious!’ ”
Li Wenliang and others opened the lid, allowing the gene company to sequence the story of this line, and another story of the clinician’s warning generated an intersection. At the Wuhan Central Hospital, doctors are not responding to routine treatment of emerging viral pneumonia patients, and hope to find answers through gene sequencing companies, while Zhang Jixian, director of the Department of Respiratory and Critical Care Medicine, Xinhua Hospital, Hubei Province, adjacent to the South China Seafood Market, December 26 Four consecutive unidentified pneumonia cases were received on the day. On December 27, Zhang Jixian reported the discovery of four “unknown viral pneumonias” to the hospital, and the hospital reported to the Jianghan CDC.
On December 28-29, Xinhua Hospital treated three more patients from the South China Seafood Market. They had similar symptoms of viral pneumonia. According to subsequent reports such as the Wuhan Evening News, at 1 pm on December 29, Xia Wenguang, deputy director of Xinhua Hospital, convened ten experts to discuss the seven cases. The experts agreed that the situation was unusual, and Xia Wenguang went directly to the provincial and municipal health authorities. Report from the CDC. Also reported on the same day was the Public Health Department of Wuhan Central Hospital. In the afternoon of the same day, the Hubei Province, Wuhan City Health and Health Commission’s Disease Control Office notified the provincial, city, and district level three disease control centers, Xinhua Hospital, and the Central Hospital Houhu Hospital to treat multiple patients with unknown pneumonia with a history of seafood market exposure. Start emergency response workflow. Hubei Provincial CDC and Wuhan CDC started epidemiological investigations with the CDCs in Jianghan District, Qiaokou District, and Dongxihu District. Huang Chaolin, deputy director of Wuhan Jinyintan Hospital, came to Xinhua Hospital and took six Of the patients, Wuhan Tongji Hospital also transferred the aforementioned patient who was the first genetic test in the central hospital to Jinyintan Hospital.
On December 30, the third-level disease control center formed the “Report on the Investigation and Disposal of Multiple Pneumonia Cases Reported by the Hospital in the South China Seafood Market”. On the same day, the Wuhan Municipal Health and Health Commission issued an internal notice, mentioning that many medical institutions in Wuhan did have multiple unexplained pneumonia cases in succession, and was related to the Wuhan South China Seafood Wholesale Market, requiring medical institutions to report those who had received consultations in the past week. Patients with similar characteristics of unexplained pneumonia.
The Wuhan Municipal Health Commission’s “Emergency Notice on Doing a Good Job in the Treatment of Unexplained Pneumonia” triggered by Zhang Jixian’s insistence on reporting was soon exposed on the Internet, along with WeChat warnings from doctors such as Li Wenliang who saw the gene sequencing report. Let the epidemic information originated in Wuhan be transmitted to the outside world for the first time.
Warning from Shanghai
Another case sample from Wuhan Central Hospital comes from Houhu Hospital, which is also adjacent to the South China Seafood Market. The patient, also named Chen, is a 41-year-old self-employed member of the seafood market in Quanzhou, Fujian. He suffered from high fever of 40 ° C, systemic aches and pains, cough, sputum, shortness of breath, and shortness of breath after experiencing cold on December 20. He was hospitalized in Houhu District of Wuhan Central Hospital with “fever cause, lung infection” on December 30th. The hospital took a bronchoscope sample on December 30th. An extra sample of respiratory lavage fluid was left in the refrigerator at -80. ° C environment.
“The reason why we have kept one more sample is because we have been involved in major national science and technology projects of China’s major natural epidemic virus, such as Shanghai Public Health Clinical Center affiliated to Fudan University (hereinafter referred to as Shanghai Public Health Center) and Wuhan Center for Disease Control and Prevention. Resources’ project cooperation, cooperation agreement has been signed for five years in a row, Wuhan City Center for Disease Control is responsible for the collection of clinical samples and environmental specimens in Central China, and regularly sent to Shanghai Public Health Center for pathogen detection, they have biological safety The third-level (BSL-3) laboratory has a high-throughput sequencing and bioinformatics analysis platform, and our hospital is the sentinel hospital of Wuhan Center for Disease Control and Prevention. “Professor Zhao Su of the Department of Respiratory Medicine, Wuhan Central Hospital.
On the afternoon of December 30, the samples were taken by a chief physician of Wuhan Centers for Disease Control and Prevention. On January 2nd, another researcher from Wuhan Centers for Disease Control and Prevention wrapped the samples in dry ice, iron boxes, and foam boxes, and shipped them to Shanghai by rail along with other animal specimens. On January 3, the team of Professor Zhang Yongzhen from Shanghai Public Health Clinical Center received the samples. This center belongs to Fudan University, Zhang Yongzhen is a researcher at the Institute of Infectious Diseases Prevention and Control of the Chinese Center for Disease Control and Prevention, and an adjunct professor at the Institute of Biomedicine of Fudan University and Shanghai Public Health Center. Under the funding of key research and development programs, he is engaged in scientific research such as zoonotic diseases, investigation of major natural epidemic-derived virus resources in China, and many hospitals, including Wuhan Central Hospital, Wuhan CDC, and the University of Sydney, Australia. As a member of the project team.
In the early morning of January 5, Zhang Yongzhen’s research team detected a new SARS-like coronavirus from the samples and obtained the entire genome sequence of the virus through high-throughput sequencing. The evolutionary tree drawn based on the sequencing data also confirmed the new corona in Wuhan Viruses have never been seen in history. The Shanghai Public Health Center immediately reported to the competent authorities of the Shanghai Municipal Health Commission and the National Health Commission on the same day, reminding them that the new virus is homologous to SARS and should be transmitted through the respiratory tract. It is recommended that appropriate disease control and prevention measures be taken in public. On January 6, a secondary emergency response was initiated within the China CDC.
“We have been collaborating with Wuhan Centers for Disease Control and Prevention, Wuhan Central Hospital, etc. to collect new natural epidemic viruses. This is part of our major national project, including the use of P3 laboratories. It was approved by the review. “A researcher at the Shanghai Public Health Center told Caixin reporter,” We are a regular researcher, and found by accident that it is of great importance and report it immediately. ”
At Least Nine Samples Were Collected for Inspection at the End of Last Year
Caixin reporter confirmed that it is almost in front of Guangzhou Weiyuan Gene Technology Co., Ltd. and Beijing Boao Medical Laboratory. Several gene sequencing companies have obtained samples of unknown pneumonia cases from Wuhan Hospital. This includes an industry “leading leader”, BGI, who received a gene sequencing commission from Wuhan Union Medical College Hospital on December 26, 2019. On December 29, BGI’s genetic sequencing of the case sample showed that the virus and SARS gene sequence similarity was as high as 80%, but not SARS, but a coronavirus that had not been seen before. BGI also used their SARS test kit to test the cases, and the results were negative, and it was negative for SARS.
On December 30, BGI orally notified the sequencing results to Wuhan Union Medical College Hospital, saying that the pathogen is a new coronavirus similar to SARS, and it is recommended that the hospital report to Wuhan Municipal Health Commission.
A person from BGI told Caixin reporters that when they were commissioned to sequence samples of unexplained viral pneumonia cases at the end of December, they did not know that the virus had caused clinical infections in many people, and even had the same genus. Cluster infections in a family. “We are a technology company doing gene sequencing. We accept a lot of sequencing commissions every day. When we come into contact with a large number of viruses, we also find many new viruses. There are many types of coronaviruses. Previously, there were only six coronaviruses including SARS and humans. Related, only SARS and MERS are more infectious to humans. At that time we did not know whether the virus was ‘good’ or ‘bad’. ”
BGI has a long-term cooperation with the local hospital in Wuhan. According to a survey by Caixin reporters, the local hospital in Wuhan in December 2019 sent at least 30 samples of difficult pneumonia to Huage Gene for sequencing. Huada found a total of three cases of pneumonia that belonged to the new coronavirus infection. Except for the case on December 26, two other cases were collected on December 29 and 30, respectively.
The relevant information obtained by Caixin reporters shows that on December 30 and 31, Huada conducted a high-level retest of the recently received cases. On December 31, they mixed three SARS-like coronaviruses. That is, the three viral gene sequence fragments are combined to form a mixed whole gene sequence. On January 1, the mixed new coronavirus gene sequence was provided to the China Centers for Disease Control and Prevention, and three test reports were also reported to the Wuhan Municipal Health Commission. On the same day, BGI rebuilt the entire genome, and obtained a whole genome sequence that day. On January 3, BGI completed sequencing of the entire gene sequence of the viruses in all three samples.
However, BGI did not publicly announce the genome sequences of these three samples of New Coronavirus. Caixin reporters found that as of January 19, 2020, a total of 13 samples of New Coronavirus genome sequences were uploaded on the GISAID platform. Except for Japan and Thailand, the remaining 10 are all uploaded by Chinese research institutes. From the time of sample collection, the earliest case was the one collected on December 24, 2019 and uploaded by the Chinese Academy of Medical Sciences Pathogen. Eight more samples were collected on December 30, respectively, Wuhan Jinyintan Hospital and Hubei Provincial Center for Disease Control (1), Jinyintan Hospital and Wuhan Institute of Virology of the Chinese Academy of Sciences (5), China CDC Virus Disease Prevention and Control Office (Article 2).
In addition, the Institute for Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention also uploaded a gene sequence for collecting samples completed on January 1, 2020.
According to the Hubei Daily, on December 30, Zhang Dingyu, the president of Jinyintan Hospital, led everyone to collect bronchoalveolar lavage fluid from the 7 patients admitted by the hospital and sent them to the Wuhan Institute of Virology, Chinese Academy of Sciences to be tested.
Based on the industry’s average detection cycle of three days, by January 2nd, the genetic sequencing results of the samples collected on December 30th above should have been obtained. In an open letter from Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology fully carried out scientific research on the new crown virus pneumonia, it was stated that on the evening of December 30, the virus received an unknown pneumonia sample from Jinyintan Hospital on the evening of December 30. The whole genome sequence of the new crown virus was determined on January 2 and uploaded to GISAID on January 11.
The above-mentioned paper published in the “Chinese Medical Journal (English version)” also shows that in the nine days from December 24, 2019 to January 1, 2020, five patients’ alveolar lavage fluid samples were collected and sent for testing. Analysis, and two of these five patients had no history of contact with the South China Seafood Market.
Of the five patients, in addition to the 65-year-old patient samples, three patients were collected on December 30, 2019. Among them, Patient No. 2 was a 49-year-old female who worked in the South China Seafood Market. She started to have a high fever and a dry cough on December 22. She developed dyspnea after five days and was hospitalized. She was admitted to the ICU on December 29. Patient No. 3 was also Female, 52 years old, onset on December 22, was hospitalized on the 29th, but she has no history of contact with the seafood market; Patient No. 4 is a 41-year-old male. He started to have a high fever, dry cough on December 16, and was hospitalized on the 22nd-this There is no history of seafood market exposure. The man is obviously the Wuchang accountant who was treated at the Wuhan Central Hospital above. The sample of alveolar lavage fluid from patient No. 5 was collected on January 1, 2020. He is a member of the South China Seafood Market. A 61-year-old man at work. He suffered from chronic liver disease and abdominal myxoma. He had fever, cough, and dyspnea for seven days. He was admitted to a local hospital. He started to use ECMO for rescue on January 2 and died.
According to the paper, a new coronavirus was identified in the laboratory in this way. It has 79% similarity to the nucleotide sequence of SARS virus. It is phylogenetically closest to the SARS-like coronavirus carried by bats, but forms Coronavirus beta strain sequence of a single evolutionary branch. After carrying out virus isolation, morphological confirmation and serological testing, the new pathogen was confirmed to be a new coronavirus. The amino acid sequence of this virus-receptor binding domain is similar to that of SARS coronavirus, indicating that the two viruses may bind to the same receptor on human cells.
Looking back on the days from the end of December 2019 to the beginning of January this year, it should have been a crucial moment in determining the fate of countless people. But at that time, the public did not know the consequences of the virus in the future.
A source from a gene sequencing company revealed that on January 1, 2020, he received a phone call from an official of the Health Commission of Hubei Province, informing him that samples of cases of new coronary pneumonia in Wuhan were submitted for inspection and could not be re-examined. Existing case samples must be destroyed, sample information cannot be disclosed, and related papers and related data cannot be released to the public. “If you detect it in the future, you must report it to us.”
On January 3, the General Office of the National Health and Medical Commission issued a “Notice on Strengthening the Management of Biological Sample Resources and Related Scientific Research Activities in the Prevention and Control of Major Outbreak Infectious Diseases.” (2020) No. 3 states that according to the recent samples of Wuhan pneumonia cases, based on the current knowledge of pathogenic characteristics, transmission, pathogenicity, clinical data and other information, before further clarifying the pathogenic information, temporarily follow the highly pathogenic pathogenic microorganisms. (Second category) For management, the transportation of relevant samples should be in accordance with the requirements of the “Ministry of Health ’s Highly Pathogenic Pathogenic Microorganism Bacteria (Poison) Species or Samples Transport Management Regulations”; the pathogen-related experimental activities Development of a biological safety laboratory of protection level.
Document No. 3 further stipulates that all relevant institutions shall provide biological samples to designated pathogen detection institutions to conduct pathogenic testing and complete the transfer procedures in accordance with the requirements of the health and health administrative departments at or above the provincial level; without approval, they may not submit to other institutions and individuals without authorization Provide biological samples and related information; Institutions and individuals who have obtained biological samples of relevant cases from relevant medical and health institutions should immediately destroy the samples in situ or send them to a depository established by the state for safekeeping, and properly keep records of experimental activities and experiments Result information; during the epidemic prevention and control work, the information generated by various types of institutions undertaking pathogenic testing tasks is a special public resource. No institution or individual may publish information about the results of pathogenic testing or experimental activities without authorization. Approved by the entrusted department.
As for which agencies are “designated pathogen detection agencies”, the document does not mention them. Some virologists revealed that even the Wuhan Institute of Virology of the Chinese Academy of Sciences was once required to stop pathogen detection and destroy existing samples. “Because of the current” Infectious Disease Prevention and Control Law, “laboratory testing, diagnosis, and pathogenic identification of infectious diseases are at all levels. The statutory responsibilities of disease prevention and control institutions, only national and provincial disease control system institutions have the right to conduct infectious disease etiology identification. The Wuhan Institute of Virology of the Chinese Academy of Sciences is obviously not included, let alone those unauthorized commercial scientific research institutions. ”
Perhaps because of this, the Chinese Academy of Sciences Institute of Virology, which received the virus samples on December 30, performed virus isolation on January 1, 2020, completed the virus gene sequencing on January 2, and isolated the virus strain on January 5. The national virus resource library was put into storage and standardized preservation was completed on the 9th. These apparently day-to-day research work has not been announced to the public. Only in February when faced with rumors and attacks from the outside world, a word-only disclosure was given.
On January 9th, CCTV reported that the “Wuhan Viral Pneumonia Pathogen Test Preliminary Evaluation Expert Group”, mainly based on the China Centers for Disease Control and Prevention, determined that the pathogen was a new type of coronavirus. “As of January 21, 2020, the laboratory A new type of coronavirus was detected, and the whole genome sequence of the virus was obtained. A total of 15 cases of positive results of the new type of coronavirus were detected by nucleic acid detection method. The virus was isolated from a positive patient sample, and the typical coronavirus appeared under an electron microscope. form.”
On January 11, Zhang Yongzhen’s research team shared the viral genome sequence information on Virologic.org website and GenBank, the first team in the world to publish the viral sequence.
On the evening of the same day, the National Health and Medical Commission announced that China would share the sequence information of the new crown virus gene with WHO. The next day, five other viral genome sequences from different patients were released by a group led by the National Health Commission on the global shared influenza virus database GISAID. For which agency did the new coronavirus gene sequence information shared with WHO come from? Gao Fu, director of the China Centers for Disease Control and Prevention, responded to Caixin reporters that the gene sequences came from tripartite institutions, the China Centers for Disease Control and Prevention, the Chinese Academy of Medical Sciences and the Chinese Academy of Sciences. This is a joint research project. The WHO says it has obtained more detailed information on unexplained viral pneumonia in Wuhan from the National Health Commission of China, including information on the sequence of novel coronavirus genes detected in cases, which is important for the development of specific diagnostic tools in other countries significance.
At this time, it is not necessary to look into who first picked the pearl on the crown of science, because 15 days have passed since the first case of genetic sequencing confirmed the new crown virus.
On January 11th, the Wuhan Health and Health Commission stopped updating for several days, and for the first time renamed “viral pneumonia of unknown cause” to “new coronavirus-infected pneumonia”, saying that as of 14:00 on January 10, 2020, Initial diagnosis of 41 cases of new coronary pneumonia. On the same day, the “two sessions” of Hubei were held. Until the end of the “two sessions” in Hubei on January 17, this number has not increased.
Caixin reporter Zhao Jinzhao and intern reporter Huang Yuxin also contributed to this article
Tracking the Source of Novel Coronavirus Gene Sequencing: When the Alarm Goes Off
(Jennifer’s note: The following is the English translation mainly done by google translate of a report on a Chinese website at https://web.archive.org/web/20200226154223/http://china.caixin.com/2020-02-26/101520972.html)
Caixin.com (Reporter Gao Yu, Peng Yanfeng, Yang Rui, Feng Yuding, Ma Danmeng) Tracing to the source, as of February 24, more than 2660 people have died and more than 77,000 people have been diagnosed with the novel coronavirus, a novel coronavirus similar to SARS. When was it found? Caixin reporters conducted interviews from various sources and sorted out relevant papers and database materials. By piecing together all sorts of information, the full picture is gradually emerging.
All kinds of evidence show that before the end of December last year, no less than nine samples of unknown pneumonia cases were collected from hospitals in Wuhan. Gene sequencing showed that the pathogen was a SARS-like coronavirus. These test results were reported back to the hospital and reported to the Health Commission and Disease Control System. Until January 9th, CCTV reported that the “Wuhan Viral Pneumonia Pathogen Testing Results Preliminary Evaluation Expert Group” officially announced the pathogen as “novel coronavirus”.
The Test Result of the First Case Came Out as Early as Dec. 27
On December 15, 2019, a 65-year-old male delivery man in the South China Seafood Market started having a fever. On December 18, he came to the emergency department of the Wuhan Central Hospital (Nanjing Road District) 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 generic term for pneumonia caused by a variety of microorganisms such as bacteria, viruses, chlamydia, and mycoplasma. The main clinical symptoms are cough, with or without sputum, and chest pain.
On December 22, the patient became iller and entered the ICU. Doctors used various antibiotics to treat him, but without any good result. Professor Zhao Su, the chief physician of the Department of Respiratory Medicine of Wuhan Central Hospital, told Caixin reporter that on December 24, a deputy chief physician of Respiratory Medicine took a bronchoscopy sample from the patient, and then sent the patient’s alveolar lavage fluid sample to the first 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 find pathogens. Alveolar lavage is a treatment that removes inflammatory secretions in the 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 throat swabs.
Weiyuan Gene is the full name of Guangzhou Weiyuan Gene Technology Co., Ltd., established in June 2018. Its job advertisement states that it focuses on precision medicine in oncology and infectious etiology, and has a sequencing platform (NGS) based on second-generation high-throughput sequencing technology.
“Since the start of BGI’s sequencing technology, many gene sequencing companies have appeared in China. In recent years, at our various medical seminars, the second-generation high-throughput gene sequencing technology has been continuously introduced. These companies have also sent medicines. Delegates went to major hospitals to preach. “Zhao Su told Caixin reporter. BGI (300676.SZ) is called Shenzhen BGI Gene Co., Ltd., formerly known as Beijing BGI Gene Research Center, and was established in 1999. It has successively completed a number of international human genome projects in China, rice and the giant panda genome project, with genomic research with international advanced level. In July 2017, it was listed on the GEM under the title of “The First Gene Sequencing Unit” and is the world’s largest genomics R & D institution.
Another doctor from Wuhan Union Medical College Hospital also introduced, “One test, with 6 million base sequences, costs 3,000 yuan. If with 3000 yuan’s cost, we can find out what virus or bacteria the pathogen is, it may save lives.”
Generally speaking, the gene sequencing company should feedback the test results three days later, that is, December 27, but Weiyuan Gene did not give a written report. “They just called us and said it was a new coronavirus.” Zhao Su said. At this time, the patient was transferred to Wuhan Tongji Hospital on December 25.
On February 21, 2020, the genetic test information of this case was disclosed by an article of WeChat account “Wei Yuan Gene”. The official article wrote that the Chinese Journal of Medical Sciences (English version) published a paper on January 27, introducing the discovery of new coronaviruses, and “Wei Yuan Gene” involved in the early discovery of new coronaviruses.
The aforementioned paper published in Chinese Medical Journal (English version) refers to the article “Identifying a New Coronavirus that Causes Severe Pneumonia in Humans: A Descriptive Study” published on January 29. The authors are from the Institute of Pathogen Biology of the Chinese Academy of Medical Sciences / Peking Union Medical College (hereinafter referred to as the Institute of Pathogens of the Chinese Academy of Medical Sciences), 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, and CEO Yongjun Li and chief operating officer Wang Xiaorui are the authors. Li Yongjun was a former bioinformatics 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 five patients with severe pneumonia at Jinyintan Hospital of Wuhan, Hubei Province, and performed pathogenic metagenomics (mNGS) analysis. As a result, a coronavirus with 79% similarity to the nucleotide sequence of the SARS virus had never been reported in these samples. The article shows that among the samples of these five patients, the earliest clinical sample for genetic sequencing was a 65-year-old patient sample collected on December 24. He developed symptoms on December 15 with symptoms of high fever, cough, and low sputum. He was admitted on the 18th and admitted to the ICU on December 22. After 16 days, she continued to have a high fever and developed severe shortness of breath.
Agreeing with the above information is also an article entitled “Recording the First Discovery of a New Coronavirus” published by WeChat account “Hill Dog” on January 28. The author claimed to work in a private enterprise located in Huangpu, Guangzhou in the message area. The article records: “I just went to work on December 26, 2019, and I would like to take a look at the results of the automatic interpretation of mNGS pathogenic microorganisms as usual. As a surprise, It was found that one sample reported a sensitive pathogen, SARS coronavirus, with dozens of sequences, and this sample only had such a meaningful pathogen. I was anxious, and 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 exploration version suggest that this pathogen is most similar to Bat SARS like coronavirus, with an overall similarity of 87% The similarity with SARS is about 81%. ”
According to the author, the sample collection time for this patient was December 24th. The article mentioned, “The front-end feedback is that this patient is seriously ill and is anxious to test the results, but such a major pathogen cannot be reported easily. At noon, I had an emergency meeting with several leaders and decided to continue in-depth analysis and delay the release of reports. Share the data with the Chinese Academy of Medical Sciences for analysis. ” The Institute of Pathogens of the Chinese Academy of Medical Sciences is one of the authors of the above-mentioned “Chinese Medical Journal (English Version)” thesis and Li Yuanjun, CEO of Weiyuan Gene, previously served as the Institute of Pathogens of the Chinese Academy of Medical Sciences, directly under the director 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 Pathogens, Chinese Academy of Medical Sciences. “It can basically be confirmed that this patient’s sample does indeed contain a new virus similar to Bat SARS like coronavirus.” 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 relevant personnel of the experimental operation conducted relevant monitoring. The doctor had been communicated before noon, and the patient was also isolated. ”
“It should be that we discovered this new coronavirus for the first time.” The article “Little Dog” also gave a screenshot of the GISAID database. “From the data submitted on the GISAID database website, it is also us that collected the earliest samples.”
GISAID is a global influenza virus sharing data platform. After registration, researchers can upload the virus gene sequences they extracted. Each strain will have a unique number, and the time of collection, submission date, submission laboratory, etc. will also be recorded. Caixin reporters found that according to the time of sample collection, the earliest sequence of a new coronavirus gene on GISAIDS was collected on December 24, 2019, and uploaded by the Institute of Pathogens of the Chinese Academy of Medical Sciences on January 11. It can be found by comparing the number, name, etc. This is the sample sequence of their company participating in the test marked in the screenshot of the article “Little Dog”.
The article also mentioned that on December 27th and 28th, the company’s leaders communicated with the hospital and the disease control (department) by phone. On the 29th and 30th, they even went to Wuhan to personally report and exchange all the analysis results with the leaders of the hospital and disease control center. Including all our analysis results and the analysis results of the Institute of Pathogens of the Academy of Medical Sciences. Everything is under intense, confidential, and strict investigation (at this time, the hospital and the disease control person already knew that there were many similar patients. After we communicated the test results, emergency response has begun). ”
The above-mentioned sample owner who completed the earliest genetic sequencing was later killed at Jinyintan Hospital. The research results of the new virus were detected 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 “unknown cause of pneumonia” from Wuhan Central Hospital were sent to different institutions for gene sequencing. The test results of the two cases had a significant impact on the disclosure of the epidemic in different ways.
On December 27, a 41-year-old man named Chen went to the Nanjing Road Hospital of Wuhan Central Hospital for treatment. “He is an accountant and lives in Wuchang. He has never been to the South China Seafood Market in Hankou. He started to have a fever on December 16 without any obvious cause. The maximum body temperature was 39.5 ° C, accompanied by palpitations, chest tightness, difficulty breathing after exercise, and physical strength. Significant decline, first seeing the doctor at Jiangxia District First People’s Hospital on December 22, did not improve. “Zhao Su told Caixin reporter,” He is an acquaintance of a doctor in our hospital, transferred to our hospital on the 27th, also an emergency department Closed. “On the evening of December 27, the patient took a bronchoscope sample in the ICU of the hospital’s respiratory department, and this time the sample was sent to another Beijing Boao Medical Laboratory Co., Ltd., which was engaged in NGS testing.
On December 30, Beijing Boao Medical Laboratory reported the patient’s report to the doctor, and the test result was “SARS coronavirus”.
The Beijing Boao Medical Laboratory’s test report obtained by reporter Cai Caixin showed that high-confidence positive indicators of SARS coronavirus and Pseudomonas aeruginosa were detected in the patient’s sample. The explanation of SARS coronavirus is: a single-stranded positive-strand RNA virus, which spreads by close droplets or contacts the respiratory secretions of patients, which can cause a significant infectivity and can accumulate multiple organs Systemic pneumonia, also known as atypical pneumonia.
“Their gene bank is not complete enough, or it may not have been reviewed, so they made a small mistake. In fact, it is not the same thing as SARS, or a new type of coronavirus.” A genetic sequencing expert told Caixin reporter.
However, it is this test report that made a small mistake, which directly caught the attention of doctors in Wuhan, sounded the public whistle through social media, and saved a considerable number of people’s lives to a certain extent.
On December 30th, the test report of Beijing Boao Medical Laboratory appeared in the WeChat of the doctor in Wuhan Central Hospital. At 17:48 on the evening of the same day, Li Wenliang, an ophthalmologist of Wuhan Central Hospital, released a message among the classmates: “7 cases of SARS were confirmed in the South China Fruit and Seafood Market, and they were isolated in the emergency department of our hospital.” At 19:39, the Wuhan Red Cross Hospital neurologist Liu Wen published a message in his work WeChat group “Xiehe Honghui Shennei”, saying: “Just a case of coronal infectious virus pneumonia was confirmed in Houhu District of the Second Hospital (that is, Wuhan Central Hospital). Maybe it will be isolated in southern China.” “SARS has been basically determined, nurses and sisters should not go out to shake.” At 20:48, Xie Linka, a doctor at the Cancer Center of Wuhan Union Medical College, posted a message on the WeChat group of the Cancer Center. “Don’t go to the South China Seafood Market in the near future. It is happening now. With many people suffering from unexplained pneumonia (similar to SARS), today our hospital has treated several cases of pneumonia patients in the South China Seafood Market. Everyone should pay attention to wearing masks and ventilation “-all three doctors have been cautioned by the police since then.
On the same day, the author of the “Little Dog” in Huangpu, Guangzhou, was also informed of the above news, and he wrote: “By December 30th, I heard that there were still many patients with similar symptoms, and the nerves broke down again. It ’s tense. Especially, it may be the afternoon of the 30th. A friend may have detected the same virus in the sample of another patient, but they sent a report that the SARS coronavirus was detected, and the news was detonated instantly. Now … the friends shared the sequence for us to analyze. I analyzed it and it was indeed the same virus! The first idea in the subconscious was ‘this virus is contagious!’ ”
Li Wenliang and others opened the lid, allowing the gene company to sequence the story of this line, and another story of the clinician’s warning generated an intersection. At the Wuhan Central Hospital, doctors are not responding to routine treatment of emerging viral pneumonia patients, and hope to find answers through gene sequencing companies, while Zhang Jixian, director of the Department of Respiratory and Critical Care Medicine, Xinhua Hospital, Hubei Province, adjacent to the South China Seafood Market, December 26 Four consecutive unidentified pneumonia cases were received on the day. On December 27, Zhang Jixian reported the discovery of four “unknown viral pneumonias” to the hospital, and the hospital reported to the Jianghan CDC.
On December 28-29, Xinhua Hospital treated three more patients from the South China Seafood Market. They had similar symptoms of viral pneumonia. According to subsequent reports such as the Wuhan Evening News, at 1 pm on December 29, Xia Wenguang, deputy director of Xinhua Hospital, convened ten experts to discuss the seven cases. The experts agreed that the situation was unusual, and Xia Wenguang went directly to the provincial and municipal health authorities. Report from the CDC. Also reported on the same day was the Public Health Department of Wuhan Central Hospital. In the afternoon of the same day, the Hubei Province, Wuhan City Health and Health Commission’s Disease Control Office notified the provincial, city, and district level three disease control centers, Xinhua Hospital, and the Central Hospital Houhu Hospital to treat multiple patients with unknown pneumonia with a history of seafood market exposure. Start emergency response workflow. Hubei Provincial CDC and Wuhan CDC started epidemiological investigations with the CDCs in Jianghan District, Qiaokou District, and Dongxihu District. Huang Chaolin, deputy director of Wuhan Jinyintan Hospital, came to Xinhua Hospital and took six Of the patients, Wuhan Tongji Hospital also transferred the aforementioned patient who was the first genetic test in the central hospital to Jinyintan Hospital.
On December 30, the third-level disease control center formed the “Report on the Investigation and Disposal of Multiple Pneumonia Cases Reported by the Hospital in the South China Seafood Market”. On the same day, the Wuhan Municipal Health and Health Commission issued an internal notice, mentioning that many medical institutions in Wuhan did have multiple unexplained pneumonia cases in succession, and was related to the Wuhan South China Seafood Wholesale Market, requiring medical institutions to report those who had received consultations in the past week. Patients with similar characteristics of unexplained pneumonia.
The Wuhan Municipal Health Commission’s “Emergency Notice on Doing a Good Job in the Treatment of Unexplained Pneumonia” triggered by Zhang Jixian’s insistence on reporting was soon exposed on the Internet, along with WeChat warnings from doctors such as Li Wenliang who saw the gene sequencing report. Let the epidemic information originated in Wuhan be transmitted to the outside world for the first time.
Warning from Shanghai
Another case sample from Wuhan Central Hospital comes from Houhu Hospital, which is also adjacent to the South China Seafood Market. The patient, also named Chen, is a 41-year-old self-employed member of the seafood market in Quanzhou, Fujian. He suffered from high fever of 40 ° C, systemic aches and pains, cough, sputum, shortness of breath, and shortness of breath after experiencing cold on December 20. He was hospitalized in Houhu District of Wuhan Central Hospital with “fever cause, lung infection” on December 30th. The hospital took a bronchoscope sample on December 30th. An extra sample of respiratory lavage fluid was left in the refrigerator at -80. ° C environment.
“The reason why we have kept one more sample is because we have been involved in major national science and technology projects of China’s major natural epidemic virus, such as Shanghai Public Health Clinical Center affiliated to Fudan University (hereinafter referred to as Shanghai Public Health Center) and Wuhan Center for Disease Control and Prevention. Resources’ project cooperation, cooperation agreement has been signed for five years in a row, Wuhan City Center for Disease Control is responsible for the collection of clinical samples and environmental specimens in Central China, and regularly sent to Shanghai Public Health Center for pathogen detection, they have biological safety The third-level (BSL-3) laboratory has a high-throughput sequencing and bioinformatics analysis platform, and our hospital is the sentinel hospital of Wuhan Center for Disease Control and Prevention. “Professor Zhao Su of the Department of Respiratory Medicine, Wuhan Central Hospital.
On the afternoon of December 30, the samples were taken by a chief physician of Wuhan Centers for Disease Control and Prevention. On January 2nd, another researcher from Wuhan Centers for Disease Control and Prevention wrapped the samples in dry ice, iron boxes, and foam boxes, and shipped them to Shanghai by rail along with other animal specimens. On January 3, the team of Professor Zhang Yongzhen from Shanghai Public Health Clinical Center received the samples. This center belongs to Fudan University, Zhang Yongzhen is a researcher at the Institute of Infectious Diseases Prevention and Control of the Chinese Center for Disease Control and Prevention, and an adjunct professor at the Institute of Biomedicine of Fudan University and Shanghai Public Health Center. Under the funding of key research and development programs, he is engaged in scientific research such as zoonotic diseases, investigation of major natural epidemic-derived virus resources in China, and many hospitals, including Wuhan Central Hospital, Wuhan CDC, and the University of Sydney, Australia. As a member of the project team.
In the early morning of January 5, Zhang Yongzhen’s research team detected a new SARS-like coronavirus from the samples and obtained the entire genome sequence of the virus through high-throughput sequencing. The evolutionary tree drawn based on the sequencing data also confirmed the new corona in Wuhan Viruses have never been seen in history. The Shanghai Public Health Center immediately reported to the competent authorities of the Shanghai Municipal Health Commission and the National Health Commission on the same day, reminding them that the new virus is homologous to SARS and should be transmitted through the respiratory tract. It is recommended that appropriate disease control and prevention measures be taken in public. On January 6, a secondary emergency response was initiated within the China CDC.
“We have been collaborating with Wuhan Centers for Disease Control and Prevention, Wuhan Central Hospital, etc. to collect new natural epidemic viruses. This is part of our major national project, including the use of P3 laboratories. It was approved by the review. “A researcher at the Shanghai Public Health Center told Caixin reporter,” We are a regular researcher, and found by accident that it is of great importance and report it immediately. ”
At Least Nine Samples Were Collected for Inspection at the End of Last Year
Caixin reporter confirmed that it is almost in front of Guangzhou Weiyuan Gene Technology Co., Ltd. and Beijing Boao Medical Laboratory. Several gene sequencing companies have obtained samples of unknown pneumonia cases from Wuhan Hospital. This includes an industry “leading leader”, BGI, who received a gene sequencing commission from Wuhan Union Medical College Hospital on December 26, 2019. On December 29, BGI’s genetic sequencing of the case sample showed that the virus and SARS gene sequence similarity was as high as 80%, but not SARS, but a coronavirus that had not been seen before. BGI also used their SARS test kit to test the cases, and the results were negative, and it was negative for SARS.
On December 30, BGI orally notified the sequencing results to Wuhan Union Medical College Hospital, saying that the pathogen is a new coronavirus similar to SARS, and it is recommended that the hospital report to Wuhan Municipal Health Commission.
A person from BGI told Caixin reporters that when they were commissioned to sequence samples of unexplained viral pneumonia cases at the end of December, they did not know that the virus had caused clinical infections in many people, and even had the same genus. Cluster infections in a family. “We are a technology company doing gene sequencing. We accept a lot of sequencing commissions every day. When we come into contact with a large number of viruses, we also find many new viruses. There are many types of coronaviruses. Previously, there were only six coronaviruses including SARS and humans. Related, only SARS and MERS are more infectious to humans. At that time we did not know whether the virus was ‘good’ or ‘bad’. ”
BGI has a long-term cooperation with the local hospital in Wuhan. According to a survey by Caixin reporters, the local hospital in Wuhan in December 2019 sent at least 30 samples of difficult pneumonia to Huage Gene for sequencing. Huada found a total of three cases of pneumonia that belonged to the new coronavirus infection. Except for the case on December 26, two other cases were collected on December 29 and 30, respectively.
The relevant information obtained by Caixin reporters shows that on December 30 and 31, Huada conducted a high-level retest of the recently received cases. On December 31, they mixed three SARS-like coronaviruses. That is, the three viral gene sequence fragments are combined to form a mixed whole gene sequence. On January 1, the mixed new coronavirus gene sequence was provided to the China Centers for Disease Control and Prevention, and three test reports were also reported to the Wuhan Municipal Health Commission. On the same day, BGI rebuilt the entire genome, and obtained a whole genome sequence that day. On January 3, BGI completed sequencing of the entire gene sequence of the viruses in all three samples.
However, BGI did not publicly announce the genome sequences of these three samples of New Coronavirus. Caixin reporters found that as of January 19, 2020, a total of 13 samples of New Coronavirus genome sequences were uploaded on the GISAID platform. Except for Japan and Thailand, the remaining 10 are all uploaded by Chinese research institutes. From the time of sample collection, the earliest case was the one collected on December 24, 2019 and uploaded by the Chinese Academy of Medical Sciences Pathogen. Eight more samples were collected on December 30, respectively, Wuhan Jinyintan Hospital and Hubei Provincial Center for Disease Control (1), Jinyintan Hospital and Wuhan Institute of Virology of the Chinese Academy of Sciences (5), China CDC Virus Disease Prevention and Control Office (Article 2).
In addition, the Institute for Viral Disease Control and Prevention of the Chinese Center for Disease Control and Prevention also uploaded a gene sequence for collecting samples completed on January 1, 2020.
According to the Hubei Daily, on December 30, Zhang Dingyu, the president of Jinyintan Hospital, led everyone to collect bronchoalveolar lavage fluid from the 7 patients admitted by the hospital and sent them to the Wuhan Institute of Virology, Chinese Academy of Sciences to be tested.
Based on the industry’s average detection cycle of three days, by January 2nd, the genetic sequencing results of the samples collected on December 30th above should have been obtained. In an open letter from Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan Institute of Virology fully carried out scientific research on the new crown virus pneumonia, it was stated that on the evening of December 30, the virus received an unknown pneumonia sample from Jinyintan Hospital on the evening of December 30. The whole genome sequence of the new crown virus was determined on January 2 and uploaded to GISAID on January 11.
The above-mentioned paper published in the “Chinese Medical Journal (English version)” also shows that in the nine days from December 24, 2019 to January 1, 2020, five patients’ alveolar lavage fluid samples were collected and sent for testing. Analysis, and two of these five patients had no history of contact with the South China Seafood Market.
Of the five patients, in addition to the 65-year-old patient samples, three patients were collected on December 30, 2019. Among them, Patient No. 2 was a 49-year-old female who worked in the South China Seafood Market. She started to have a high fever and a dry cough on December 22. She developed dyspnea after five days and was hospitalized. She was admitted to the ICU on December 29. Patient No. 3 was also Female, 52 years old, onset on December 22, was hospitalized on the 29th, but she has no history of contact with the seafood market; Patient No. 4 is a 41-year-old male. He started to have a high fever, dry cough on December 16, and was hospitalized on the 22nd-this There is no history of seafood market exposure. The man is obviously the Wuchang accountant who was treated at the Wuhan Central Hospital above. The sample of alveolar lavage fluid from patient No. 5 was collected on January 1, 2020. He is a member of the South China Seafood Market. A 61-year-old man at work. He suffered from chronic liver disease and abdominal myxoma. He had fever, cough, and dyspnea for seven days. He was admitted to a local hospital. He started to use ECMO for rescue on January 2 and died.
According to the paper, a new coronavirus was identified in the laboratory in this way. It has 79% similarity to the nucleotide sequence of SARS virus. It is phylogenetically closest to the SARS-like coronavirus carried by bats, but forms Coronavirus beta strain sequence of a single evolutionary branch. After carrying out virus isolation, morphological confirmation and serological testing, the new pathogen was confirmed to be a new coronavirus. The amino acid sequence of this virus-receptor binding domain is similar to that of SARS coronavirus, indicating that the two viruses may bind to the same receptor on human cells.
Looking back on the days from the end of December 2019 to the beginning of January this year, it should have been a crucial moment in determining the fate of countless people. But at that time, the public did not know the consequences of the virus in the future.
A source from a gene sequencing company revealed that on January 1, 2020, he received a phone call from an official of the Health Commission of Hubei Province, informing him that samples of cases of new coronary pneumonia in Wuhan were submitted for inspection and could not be re-examined. Existing case samples must be destroyed, sample information cannot be disclosed, and related papers and related data cannot be released to the public. “If you detect it in the future, you must report it to us.”
On January 3, the General Office of the National Health and Medical Commission issued a “Notice on Strengthening the Management of Biological Sample Resources and Related Scientific Research Activities in the Prevention and Control of Major Outbreak Infectious Diseases.” (2020) No. 3 states that according to the recent samples of Wuhan pneumonia cases, based on the current knowledge of pathogenic characteristics, transmission, pathogenicity, clinical data and other information, before further clarifying the pathogenic information, temporarily follow the highly pathogenic pathogenic microorganisms. (Second category) For management, the transportation of relevant samples should be in accordance with the requirements of the “Ministry of Health ’s Highly Pathogenic Pathogenic Microorganism Bacteria (Poison) Species or Samples Transport Management Regulations”; the pathogen-related experimental activities Development of a biological safety laboratory of protection level.
Document No. 3 further stipulates that all relevant institutions shall provide biological samples to designated pathogen detection institutions to conduct pathogenic testing and complete the transfer procedures in accordance with the requirements of the health and health administrative departments at or above the provincial level; without approval, they may not submit to other institutions and individuals without authorization Provide biological samples and related information; Institutions and individuals who have obtained biological samples of relevant cases from relevant medical and health institutions should immediately destroy the samples in situ or send them to a depository established by the state for safekeeping, and properly keep records of experimental activities and experiments Result information; during the epidemic prevention and control work, the information generated by various types of institutions undertaking pathogenic testing tasks is a special public resource. No institution or individual may publish information about the results of pathogenic testing or experimental activities without authorization. Approved by the entrusted department.
As for which agencies are “designated pathogen detection agencies”, the document does not mention them. Some virologists revealed that even the Wuhan Institute of Virology of the Chinese Academy of Sciences was once required to stop pathogen detection and destroy existing samples. “Because of the current” Infectious Disease Prevention and Control Law, “laboratory testing, diagnosis, and pathogenic identification of infectious diseases are at all levels. The statutory responsibilities of disease prevention and control institutions, only national and provincial disease control system institutions have the right to conduct infectious disease etiology identification. The Wuhan Institute of Virology of the Chinese Academy of Sciences is obviously not included, let alone those unauthorized commercial scientific research institutions. ”
Perhaps because of this, the Chinese Academy of Sciences Institute of Virology, which received the virus samples on December 30, performed virus isolation on January 1, 2020, completed the virus gene sequencing on January 2, and isolated the virus strain on January 5. The national virus resource library was put into storage and standardized preservation was completed on the 9th. These apparently day-to-day research work has not been announced to the public. Only in February when faced with rumors and attacks from the outside world, a word-only disclosure was given.
On January 9th, CCTV reported that the “Wuhan Viral Pneumonia Pathogen Test Preliminary Evaluation Expert Group”, mainly based on the China Centers for Disease Control and Prevention, determined that the pathogen was a new type of coronavirus. “As of January 21, 2020, the laboratory A new type of coronavirus was detected, and the whole genome sequence of the virus was obtained. A total of 15 cases of positive results of the new type of coronavirus were detected by nucleic acid detection method. The virus was isolated from a positive patient sample, and the typical coronavirus appeared under an electron microscope. form.”
On January 11, Zhang Yongzhen’s research team shared the viral genome sequence information on Virologic.org website and GenBank, the first team in the world to publish the viral sequence.
On the evening of the same day, the National Health and Medical Commission announced that China would share the sequence information of the new crown virus gene with WHO. The next day, five other viral genome sequences from different patients were released by a group led by the National Health Commission on the global shared influenza virus database GISAID. For which agency did the new coronavirus gene sequence information shared with WHO come from? Gao Fu, director of the China Centers for Disease Control and Prevention, responded to Caixin reporters that the gene sequences came from tripartite institutions, the China Centers for Disease Control and Prevention, the Chinese Academy of Medical Sciences and the Chinese Academy of Sciences. This is a joint research project. The WHO says it has obtained more detailed information on unexplained viral pneumonia in Wuhan from the National Health Commission of China, including information on the sequence of novel coronavirus genes detected in cases, which is important for the development of specific diagnostic tools in other countries significance.
At this time, it is not necessary to look into who first picked the pearl on the crown of science, because 15 days have passed since the first case of genetic sequencing confirmed the new crown virus.
On January 11th, the Wuhan Health and Health Commission stopped updating for several days, and for the first time renamed “viral pneumonia of unknown cause” to “new coronavirus-infected pneumonia”, saying that as of 14:00 on January 10, 2020, Initial diagnosis of 41 cases of new coronary pneumonia. On the same day, the “two sessions” of Hubei were held. Until the end of the “two sessions” in Hubei on January 17, this number has not increased.
Caixin reporter Zhao Jinzhao and intern reporter Huang Yuxin also contributed to this article