Evaluating Incidence and Impact Estimates of the COVID-19 Outbreak from Wuhan before Lockdown
1 Evaluating Incidence and Impact Estimates of the Coronavirus Outbreak from Wuhan before Lockdown
Mai He, M.D., Ph.D., Li Li, M.A. , Louis P. Dehner, M.D. Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA 2.
AT&T, Bedminster, NJ 07921, USA
Corresponding author:
Mai He, M.D., Ph.D. Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA Phone: (314) 273-1328 Email: [email protected] Abstract
Background: Wuhan, China was the original epicenter of COVID-19 pandemic. The goal of the current study is to understand the infection transmission dynamics before intervention measures were taken, such as issuing a lockdown for the city and other social distancing policies. Methods: Data and key events were searched through pubmed for medical literature and internet for Chinese government announcements and Chinese media reports. Epidemiological data including R0 and infection were calculated using data extracted from variety of data sources. Results: We established a timeline emphasizing evidence of human-to-human transmission. By January 1, 2020, Chinese authorities had been presented convincing evidence of human-to-human transmission; however, it was until January 20, 2020 that this information was shared with the public. Our study estimated that there would have been 10,989 total infected cases if interventions were taken on January 2, 2020, vs 239,875 cases when lockdown was put in place on January 23, 2020. Conclusions: China’s withholding of key information about the 2020 COVID-19 pandemic and its delayed response ultimately led to the largest public health crisis of this century and could have been avoided with earlier countermeasures. Introduction
The COVID-19 outbreak that originated from Wuhan, a major transportation hub of China, had caused more than eight million confirmed cases and 444,563 deaths in the world as of June 17, 2020 [1]. Multiple countries reported having their first cases imported from Wuhan or by a returning visitor to Wuhan [2-7]. Thus, it is important to understand the infection transmission dynamics within the epicenter where the virus first originated, especially before intervention measures were taken such as issuing a lockdown of the city and other social distancing policies. In spite of the worldwide interest in understanding the initial phase of the pandemic in Wuhan, researchers’ efforts have been hampered by lack of transparency including the lack of comprehensive and reliable data from this period. By the time of the lockdown on January 23,2020, the Chinese official report for the COVID infection in Wuhan is 495 cases. However, media reports from China suggest that the official confirmed cases in Wuhan before and around the lockdown were significantly underreported. This under-reporting seems to be due to multiple factors, such as limitation of testing and surveillance capability [8,9]; limited quantity of test kits provided to local hospitals [10] and generally low testing accuracy (low sensitivity, 30-60%) [11]. More importantly, government policies and intervention, such as the different versions of diagnostic criteria, seem to have a heavy influence on the information sharing and preparation for the pandemic [12]. The current study investigates the early outbreak through search and screening into various types information, including interviews with those who were in direct contact with patients, Chinese media reports and government reports. We found that the key information of human to human transmission had not been reported by the Chinese government for at least three weeks, despite convincing evidence. We provide our estimates of the impact of this delay of three weeks and other epidemiological parameters related to COVID-19 outbreak in Wuhan, before the lockdown and other public quarantine measures on January 23, 2020. Methods
Data Collection
In an effort to reconstruct what happened before and during the lockdown in Wuhan, we screened media reports published in mainland China from January to April 2020, covering the details about various events and measures taken by local hospitals and government on various levels concerning the Wuhan lockdown. We have complied the epidemic relevant events into a timeline so that the scientific community will have information that can potentially impact understanding the dynamics of the COVID-19 virus in Wuhan, China. We searched and profiled data through the following different information channels. 1). Pubmed search using keyword “COVID-19”. Search results were screened for daily incidence by PCR diagnosis from admitted patients. Two references were found [13, 14]. [Appendix A, column B]. 2). Screening of published Chinese media reports with recounts from local physicians and hospitals. Search results were screened for daily and total hospitalization cases including the PCR confirmed cases and patients with high suspicion of COVID infection with severe symptoms. We found the following Chinese media reports and government announcements [15-19] [Appendix A, column C]. Data Classifications
We have created three data categories for our calculations: A: Hospitalized patients with COVID infection confirmed by PCR in Wuhan citywide. B: Hospitalized patients due to COVID infection in Wuhan citywide (including highly suspicious clinical cases not yet confirmed by PCR or local diagnosis criteria). C: Daily symptomatic incidences based on daily cases with COVID patterns identified by radiologists from CT reading rooms from two similarly sized Grade III Level A (tertiary) hospitals.
Results I. Timeline of COVID-19 Outbreak Before Lockdown and Chinese Government’s Reaction
A brief timeline of COVID-19 outbreak, focusing on features of human-to-human transmission, before Wuhan lockdown on January 23, 2020, is listed in Figure 1 [20, 21] (for a more comprehensive timeline and its references, see Appendix B).
I.I Patients in family clusters suggestive of human to human transmission
On December 27, 2019, an elderly couple presenting with fever and dyspnea was admitted to Wuhan Xinhua Hospital ICU. On the next day, the son of this couple was called to Xinhua Hospital. The CT imaging of all three in the family showed similar findings. This family cluster demonstrated an obvious clue of “human to human transmission.” ICU chief, Dr. Zhang Jixian reported these three cases to the hospital leadership. On December 29, the vice president of the Xinhua Hospital, Dr. Xia Wenguang called for a clinical conference on seven similar cases, including this family cluster of three. On the same day, Dr. Xia reported to the City and Provincial Health Commissions and CDCs. He asked for starting emergency protocol activation. On December 29, 2019, the ER in Wuhan Central Hospital reported four similar cases to the Hospital Public Health Office, which reported to local county CDC. Among these patients, there was a pair of mother-son, another example of human-to-human transmission. On 12/30/2019, one physician in Xinhua Hospital reported symptoms. This was confirmed on Jan 11, and she is the 2nd case of a medical staff infected in Xinhua Hospital. I.II. Next-generation sequencing (NGS) of airway samples suggestive of SARS-like coronavirus
On December 27.2019, the NGS result of patient A was orally reported back to Central Hospital by Vision Medicals (Guangzhou, China) by phone, it was claimed to be a coronavirus that is “Bat SARS like”. The sequencing results of patient A were forwarded to Wuhan Institute of Virology (WIV), and WIV confirmed the high similarity to SARS-like coronavirus from bat. On December 30, 2019, Beijing CapitalBio MedLab ( 北京博奥医学 检验所 ) reported sequencing results of patient Chen 2 as “highly suspicious for SARS” to the Central Hospital. Dr. Ai Fen, ER Chief in Central Hospital, reported sequencing results to Hospital Public Health Office and Hospital Infectious Disease Department. She also forwarded the report to ER doctor’s Wechat, which triggered a chain of events spreading the warning, including message sent out by Dr. Li Wenliang. On January 1, 2020, BGI group (Huada Gene) reported sequencing results of 3 cases of pneumonia in Wuhan which harbored viral genome sequences showing 80% similarity to SARS virus to Wuhan City Health Commission. I.III. Non-acknowledgement of human-to-human transmission and intervention in case reporting
As Table 1 demonstrates, by December 30, 2019, there had been convincing evidence of human-to-human transmission, including clinical presentation of patient clusters and viral sequencing results. Despite this, on December 30,2019, the Wuhan City Health Commission issued two emergency policies, the 2nd one stating that “no one or institution is allowed to disclose information about the pneumonia (of unknown etiology) without authorization.” On December 31, 2019, the Wuhan City Health Commission announced that recent pneumonia cases seen in some hospitals were related to the Wet Market; no obvious findings of “human to human transmission” and no infection of medical staff. On December 31, 2019, the Chinese National Health Commission dispatched a panel of experts to Wuhan for investigation. After visiting Wuhan, they announced no evidence of “human to human transmission” on January 10, 2020. It was not until January 20, 2020 that the National Health Commission announced the human to human transmission by COVID-19. Three weeks passed from the emerging evidence of human-to-human transmission. During this period, Chinese physicians sensed the risk of outbreaks and reported promptly; Chinese researchers also cultured and isolated the virus and obtained the viral genome sequence. On the other hand, while the Chinese government started to communicate with international organizations, the severity was under-reported and “human to human transmission” was denied. Other counterproductive measures taken by the Chinese government included, but were not limited to, prohibiting medical staff from releasing information to public, prohibiting discussions among medical staff on the “pneumonia of unknown etiology”, prohibiting staff from wearing PPE (personal protection equipment), prohibiting 3rd party labs from doing viral sequencing, making diagnostic criteria difficult for diagnosis confirmation, deleting reported cases, disciplinary action against “whistle blowers” and closure of the lab which shared viral genome information with the international community. Wuhan local and the Chinese National CDC has implemented at least seven different versions of diagnosis criteria since the outbreak, thus making it hard to identify and understand the infection number in a consistent manner [12]. If taking infection with mild or no symptoms into account, a study estimated that 86% of infected individuals were not documented in China before January 23, 2020 [22]. Policies and interventions for reporting (holding cases for 12 days) made the confirmed cases artificially low, as reported by mainland Chinese media [15,16, 23]. I.IV. Reaction of Taiwan and Hong Kong governments
By comparison, the Hong Kong and Taiwan governments were closely monitoring and preparing for the coming epidemic during this critical time. On December 31, 2019, Taiwan inquired of China and the WHO for details about the “Atypical Pneumonia patients quarantined” with a strong suspicion of human to human transmission. Taiwan started border infections screening on direct flights from Wuhan to Taiwan. On December 31, 2019, Hong Kong media reported the presence of “new SARS” in Wuhan. The Taiwan and Hong Kong governments had press conference almost daily on the epidemic. II.
Estimation of Epidemic in Wuhan II.I. Calculation of R Assuming the ratio of symptomatic cases in the total infected population is constant, and the proportion of symptomatic patients seeking medical help remains constant over the time, we use the growth rate of hospitalized people, PCR test positives or CT positives in our dataset as the proxy for the growth rate of the infected population. R represents the average number of secondary cases that result from the introduction of a single infectious case in a totally susceptible population during the infectious period. Wallinga and Lipsitch have pointed out that the exponential growth rate (r) during the early phase of the outbreak can be used to calculate the R by using the formula R = 1/M(-r), where M is the moment generating functions of the serial interval (SI) distribution of the disease [24] . We assumed a gamma distribution for the serial interval, with 7.5 as the mean and 3.4 as standard deviation, based on a prior study of Wuhan data of the initial epidemic stage [13]. R package “ R ” is used to provide estimates of the R and its 95% confidence interval [25]. In the Feb. 3 speech, Chinese President Xi told China’s most powerful leaders that he had “continuously given verbal and written instructions” since Jan 7, and he had personally ordered the quarantine of about 60 million people in Hubei province later in January. We found PCR reported cases decreased after January 9, 2020, while no countermeasure had been taken by then. The decrease in reporting could well be driven by political reasons. Thus, we utilize (dataset A) PCR results from December 1, 2019 to January 8, 2020 (the growing portion which is less subject to political intervention) [Figure 2], R is estimated to be 3.12, with 95% confidence interval as (2.69, 3.64) [Table 2]. Patients without symptoms are highly unlikely to be tested for COVID in Wuhan, they will get CT scans only if they have symptoms that are either severe or causing respiratory distress; thus, the CT rooms readings provide samples with severe symptoms. The CT data (data set C) fit well with a Poisson log linear regression model for the daily new incidence. The coefficient of the Poisson model is 0.179 (0.151, 0.207), which implies 3.565 doubling time and higher R than the PCR based R . However, due to the limited size of this dataset, this study will mainly use the PCR based R for estimation. Based on field observation, around 60,000 more people visited febrile clinics in Wuhan from January 22 to January 27, 2020 with symptoms, and 3,883 were observed at clinics who could not be admitted due to lack of beds [Appendix A, column I]. Chinese media reported that shortage of hospital beds wasn’t eased until February 15, 2020. The growth of the hospitalized population was subject to the capability of Wuhan for adding beds dedicated to COVID patients. Thus, we are not going to use the daily incremental hospitalization for the R estimation, since it could likely produce an underestimate. II.II. Estimate of incidence in Wuhan based on the SEIR model
Susceptible–exposed–infectious–removed (SEIR) model is applied to estimate the incidences. The following epidemiologic parameters are assumed in the estimation [13]. 1.
December 1, 2019 as the initial outbreak time, January 23, 2020 is the 54 th day. 2.
2% case fatality rate (Chinese official figure of the early stage in Wuhan)
14 million population in Wuhan before lockdown [27] With the estimated 3.12 R based on the PCR results and the SEIR model, it is estimated that by January 23, 2020, Wuhan had 239,875 infected people, among them 149,170 were in the stage of incubation and were infectious. The new daily latent and infectious cases are estimated to be 23,774, 7,148 respectively on January 23, 2020. [Figures 3A] II.III. Hospital admission rate: government official report vs estimation
The Chinese official report for Wuhan suggested a 100% admission rate for COVID patients diagnosed in Wuhan, China [28]. However, it was very hard to secure a bed around the lockdown period in Wuhan, and many residents were told to go back home and self-quarantine [29]. By December 31, 2019, the officially reported admitted number is 46, our analysis estimates a total of 333 (105, 1,219) infectious cases by then, which implies 13% admission rate (46/333). On January 20, 2020, it was reported the 2,000 beds dedicated to COVID were all occupied, we estimated 14,804 (2,485,104,298) infectious cases cumulated, and a 13.5% admission rate. The above hospital admission ratio was based on the estimates of infectious cases, many infected but no longer infectious cases needed medical care as well.
III. Estimation of Impacts of the Delay of the Three Weeks
The period of the three weeks before the lockdown was a crucial time in the early stage of the epidemic. If countermeasures would have been taken on January 2, 2020, immediately after the authorities were informed about the human-to-human transmission, the epidemic development would have taken a completely different trajectory. If we assume the intervention reduces the daily contacts of the infectious by 2/3, our study estimated that there would have been 10,989 total infected cases, vs 239,875 cases when lockdown was taken place on Jan 23, Discussion
Potential impact of the delay of the critical three weeks
Some other scholars have done hypothetical studies of countermeasures. As Yang et al. suggested, using a modified SEIR and AI prediction of the epidemic trend of COVID-19 in China, “If the introduction of interventions was delayed by five days, the transmission coefficient would have been much greater due to the increase in the average number of contacts with an infected person daily.” They also pointed out that a five-day delay in implementation would have increased the epidemic size in mainland China three-fold [30]. Lai S and associates pointed out that if interventions in China could have been conducted one week, two weeks, or three weeks earlier, cases could have been dramatically reduced by 66% (IQR 50% - 82%), 86% (81% - 90%), or 95% (93% - 97%), respectively [31]. Our study has demonstrated that the delay was real, there is 21 day interval between December 31 and January 20 when China acknowledged the human to human transmission, and 24 days to January 23 when lockdown took place. The experience of Hong Kong and Taiwan has shown that the infection can be contained if actions are taken promptly [32,33]. Based on our media report screening, we did not identify any public quarantine measure taken by the government in Wuhan before January 23, 2020. Instead, communities were encouraged to continue hosting large scale gatherings to celebrate the lunar New Year. On January 18, 2020, over 40 thousand families attended the Ten Thousand Families Banquet at the Baibuting Community, none of the attendees wore masks. Three days before this event, some organizers asked to cancel the banquet, but the request was not approved [34]. In the meantime, the authorities took steps to underreport the incidence and infectivity of COVID-19 to China and the world. Emigration and estimation
In this study, we did not incorporate the dynamics of the population in Wuhan. About five million people left Wuhan before the lockdown, with a large portion happening during the week before Chinese New Year’s Day (January 25, 2020). The infected among this emigrant group got in contact with population outside Wuhan, making the susceptible number larger. Also, the higher frequency of interpersonal contacts of these emigrants before the Chinese New Year’s Day will result in a higher R . Hence, the estimation of the infected presented in this paper is likely to be an underestimate. The start date of the outbreak
In this study, we assumed the outbreak first took place on December 1, 2019. Some studies suggest an earlier date. However, Ma J reported that according to China’s internal government’s data, the first case of COVID-19 confirmed case could be traced back to November 17, 2019 [35]. The Epidemiology Working Group for NCIP Epidemic Response and Chinese Center for Disease Control and Prevention, retrospectively reported 104 cases by December31, 2019 based on data extracted from China's Infectious Disease Information System [36]. On September 18, 2019, Chinese media reported a drill by Wuhan Customs, including a case scenario of “novel coronavirus infection” [37]. The above information suggests possibilities that are not known to public. R estimation and modeling The epidemiological parameters are important for estimating the potential impact of the at least three-weeks delay in response by Chinese government. R for Wuhan has been studied by other groups. Li Q et al. from the Chinese CDC and other institutions studied the Wuhan epidemic curve up to January 4, 2020, with estimation of R0 as 2.2 [13]. Zhao S et al. applied an exponential growth model, adjusted report rate of the Chinese official data, and estimated the R0 to be between 2.24 to 3.58 [38]. A study by Sanche S and associates looked into Wuhan travelers who were confirmed infected in other provinces and estimated the Wuhan outbreak had a R0 of 5.7 (3.8–8.9) [26]. Hou J et al estimated the R0 in Wuhan to be 4.90 during the local epidemic period from December 1, 2019 to January 9, 2020, and 3.00 during the long-distance spread period due to the Spring Festival travel rush from January 10 to 22 [39]. Read JM et a.l estimated that only 5.1% of infections in Wuhan's early outbreak were identified, and R0 as 3.11 between January 1 to January 21 [40]. Wu JT et al studied cases exported from Wuhan to other cities outside of Mainland China using modelling and estimated R0 to be 2.68 [41]. Despite our efforts to extract clinical operation-related data from various types of reports, the data we have collected are still fragmented and largely incomplete due to the lack of transparency in China. Nevertheless, our PCR based R estimate 3.12 with 95% C.I (2.69, 3.64) is compatible with the previous studies. As shown in table 5, if the actual R is higher than 3.12, the case reduction brought by intervention will be more significant; if the actual R is lower, the epidemic would have been contained by January 23, 2020. Wuhan is not a homogenous city, the SEIR model at most can be used to give a crude oversimplified mathematical modelling of real-life events and estimates of the magnitude of infection. Given the nature of MCMC methods, the samples/incidences generated in our case best serve as a rough estimate of the size of the Wuhan epidemic and indicator of discrepancy from official figures. We thus acknowledge the limitations to the accuracy of our measures. Conclusion
We investigate the COVID-19 outbreak related clinical operations in Wuhan by drawing a timeline of the COVID-19 outbreak before lockdown, focusing on “human to human transmission.” This timeline demonstrates that the Chinese government did not provide critical information it possessed of human to human transmission for at least three weeks, while intervening in the case reporting. Without the three-week delay, the largest public health crisis of this century could have been avoided or controlled to a much greater degree. References:
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34. 29. “ 封城 ” 二十日里的武 汉百步 亭 Acknowledgements:
To Chinese physicians and all health care professionals, among them are my classmates, and to media reporters, for their courage and professionalism. We thank Professor Lucia Dunn at the Ohio State University for her help on data analysis and language editing of this manuscript.
Funding:
None
Declaration of interest:
The authors declare no conflict of interest. Figures legends:
Figure 1. Brief timeline of COVID-19 outbreak in Wuhan, China, before lockdown on January 23, 2020, emphasizing events related “human to human transmission” . Figure 2. Calculation of R0 based on dataset A up to January 8, 2020. Figure 3A: Estimation of COVID-19 Infection with Intervention Taken on Jan 23, 2020. Figure 3B: Estimation of Infection with Intervention Taken on Jan 2, 2020. Table 1. Evidence of “human to human” transmission in Wuhan, China, by December-31, 2019 [20,21] Hospital Case Dates Xinhua Hospital The case of family of 3 Dec 27 and 28, 2019 Central Hospital Sequencing result of “Bat SARS like” novel coronavirus reported by Guang Zhou (Vision Medical) from patient A (Dec-18-2019) Admitted on Dec 18, 2019; Sampled on Dec 24, 2019; Sequencing result reported on December 30, 2019 Central Hospital The case of mother-son pair December 29, 2019 Central Hospital Beijing (CapitalBio MedLab) reported sequencing results of patient Chen 2 as “highly suspicious for SARS”. Admitted on December 27, 2019; Reported on December 30, 2019 Xinhua Hospital One physician in Xinhua Hospital reported symptoms. This was confirmed on Jan 11, 2020 and she is the 2nd case of medical staff infection in Xinhua Hospital. December 30, 2019 Table 2: R estimation Dataset A: PCR Incidence (December 1, 2019 - January 21, 2020) 1.62 (1.53, 1.72) Dataset A: PCR Incidence (December 1, 2019 – January 8, 2020) 3.12 (2.69, 3.64) Dataset B: Hospitalized (December 1, 2019 – January 21, 2020) 2.28 ( 2.16, 2.41) Dataset C: CT (January 1, 2020 – January 21, 2020) 3.70 (3.36, 4.06) Table 3: Infection of COVID-19 from Wuhan on January 23, 2020
R0 Intervention Latent (incubation) Infectious Infected but no longer infectious Recovered Died Total infected Total infected staying Wuhan Total infected out of Wuhan 3.12 (2.69, 3.64) January 23, 2020 114,823 (15,935, 900,700) 34,347 (5,021, 272,953) 71,193 (12,423, 501,280) 19,101 (3,796, 129,551) 411 (81, 2,608) 239,875 (37,256, 1,807,092) 154,205 (23,950, 1,161,702) 85,670 (13,306, 645,390) 3.12 (2.69, 3.64) January 2, 2020 1,333 (258, 8,421) 583 (118, 3,508) 5,807 (1,536, 26,879) 3,199 (910, 13,639) 67 (19, 286) 10,989 (2,841, 52,724) 7,064 (1,826, 33,894) 3,925 (1,015, 18,830) Figure 1. Brief timeline of COVID-19 outbreak in Wuhan, China, before lockdown on January 23, 2020, emphasizing events related “human to human transmission.” Figure 2. Calculation of R0 based on dataset A up to January 8, 2020. Note: calculation was done with the epidemic calculator. http://gabgoh.github.io/COVID/index.html
Figure 3A: Estimation of COVID-19 Infection with Intervention Taken on Jan 23, 2020. Note: calculation was done with the epidemic calculator. http://gabgoh.github.io/COVID/index.html
Figure 3B: Estimation of Infection with Intervention Taken on Jan 2, 2020. Supplementary materials Table of Contents
Item Page Appendix A. Data 2 Appendix B. Timeline of COVID-19 Outbreak in Wuhan, before Lockdown on Jan 23, 2020 5 Appendix B. Tables Table 1. 20 Table 2. 21 Table 3. 22 Table 4. 23 References. 26 Appendix A. Data
A B C D E F G H I
Date New Confirmed Incidence by PCR [13,14] Hospitalized( new incidence) Inferred to be positive cases [15-19] Hospitalization (new incidence) [including confirmed and inferred] Symptomatic cases at Clinic (inferred to be positive for COVID) Total Confirmed by PCR (total of Column B by date)
Dataset A
Total Hospitalized (total of column D by date)
Dataset B
CT Clinical diagnosis daily Incidence
Dataset C
Total Symptomatic cases at Clinic (inferred to be positive for COVID) Appendix B. Timeline of COVID-19 Outbreak in Wuhan, before Lockdown on Jan 23, 2020 *Executive Summary* This timeline attempts to be comprehensive, with the main focus on “human-to-human” transmission By January 1, 2020, there had been convincing evidence of “human-to-human” transmission On January 20, 2020, Chinese communist party (CCP) government admitted “human-to-human” transmission including infection of medical staff Between January 1 and January 20, CCP government had been hiding the epidemic related information, suppressing the spread of epidemic related information and denying “human-to-human” transmission The delay of sharing with the world the true information related to the COVID-19 outbreak in Wuhan, leading to the largest public health and humanity crisis of this century Classification A : Category A described how different layers of the Chinese Communist Party (CCP) government system use various strategies to hide the truth about Wuhan COVID-19 outbreak, including all measures and policies to suppress the right moves from the first line medical staff in Wuhan. B : Category B described how the front line medical staff and other health care related professionals reacted and found out about the truth, and how they tried to manage the outbreak while blowing whistles. Basically, the “human to human transmission” and “viral genome” are the key clues that we focus this timeline on. Timeline
September 18, 2019 (09/18/2019) A: Chinese media reported a drill in Wuhan Customs. One case scenario was a case of patient with acute respiratory distress in Wuhan Airport, from a flight entering China. The patient was later diagnosed as “novel coronavirus infection”. http://k.sina.com.cn/article_2000016880_7735d5f002000krlq.html 11/17/2019 八点健 闻) 广州微 远 基因科技有限公司 ) at Guangzhou for (NGS/mNGS) sequencing. Patient A was transferred to Wuhan Tongji Hospital on Dec 25. 12/26/2019 B: Patient Chen1 visited Wuhan Central Hospital. Alveolar lavage sample was sent to Shanghai Public Health Clinical Center affiliated to Fudan University. 12/26/2019 B: Prof. Zhang Yongzhen’s team in Shanghai Public Health Clinical Center received one sample each from Wuhan Central Hospital and Wuhan CDC, respectively. [[[ From Wuhan Xinhua Hospital to Jinyintan Hospital: Series of events from 12/26-29, 2019 (for the purpose of coherence, a few day’s actions are put together): 12/26/2019 B: One patient from the Wet Market presented to Wuhan Xinhua Hospital. His symptoms included fever, cough, short of breath and “patchy ground glass” like lesions in the lungs. 12/27/2019 B: An elderly couple presented with Fever and dyspnea was admitted to Wuhan Xinhua Hospital ICU. ICU chief, Dr. Zhang Jixian reported these 3 similar cases to hospital leadership, hospital subsequently reported to local CDC in the morning. On 12/28/2019, the next day, son of the above elderly couple was called to Xinhua Hospital. The CT imaging of all three showed similar findings. This family cluster demonstrated an obvious clue of “human to human transmission”.
Dr. Xia reported to the City and Provincial Health Commissions and CDCs. He asked for starting emergency protocol activation.
A: In the same afternoon, Health commissions and CDCs from Wuhan City and Hubei Province organized an expert team to Xinhua Hospital. B. 6/7 patients in Xinhua Hospital were transferred to Wuhan Jinyintan Hospital. Patient A (the first one with sample submitted to NGS testing) from the Central also was transferred to Jinyintan Hospital. ]]] 北京博奥医学 检验所有限公司 ) for NGS testing. 12/27/2019 B: The NGS sequencing results of patient A were orally reported back to Central Hospital by Vision Medicals by phone, it was claimed to be a coronavirus that is “Bat SARS like”. , there was a pair of mother-son, another example of human-to-human transmission. B: Beijing CapitalBio MedLab ( 北京博奥医学 检验所 ) reported sequencing results of patient chen 2 as “highly suspicious for SARS”, to the Central Hospital. (华中科技大学同济医学院附属)协和医院肿瘤中心主治医师谢琳 卡 ]. 12/30/2019 B: One physician in Xinhua Hospital reported symptoms. This was confirmed on Jan 11 and she is the 2nd case of medical staff infection in Xinhua Hospital . 12/30/2019 A: Wuhan City Health Commission issued 2 emergency policies, the 2nd one stated that “ no one or institution is allowed to disclose information about the pneumonia without authorization .” 12/30/2019 A: Wuhan City Health Commission broadcasted to major hospitals internally that “1, this pneumonia is not SARS, , 3 does not cause death; 4 no medical staff infection”. (see above right) 12/30/2019 B: Wuhan Central Hospital clinical departments shared the message/instruction from Wuhan City Health Commission not to “casually announce the current situation to public or outsider, otherwise they would be seriously punished”. 12/30/2019 A: Leadership in Wuhan Central Hospital informed all division chiefs to inform their staff that they were not allowed to leak any virus related news and not allowed to wear facial masks. so far no obvious findings of “human to human transmission” and no infection of medical staff. Note: For comparison (or see Table 3). 12/31/2019 A: China reported to WHO about a series of “Pneumonia with unknown etiology” in Wuhan. A : An anonymous person in Sequencing Company reported that he received a phone call from Wuhan Health Commission on 1/1/2020 that he had to stop testing all samples from Wuhan; destroy all existing samples; should not disclose information regarding samples to public; should not publish any research or data based on the samples from Wuhan. He was told to report to the Health Commission should the company receive any sample in the future. 1/1/2020 A:
Wuhan police department announced that Wuhan Health Commission has conveyed information about Wuhan pneumonia to the general public. However, some people spread false information online, 8 of them have been summoned and proper actions taken.
BGI group (Huada Gene) reported sequencing results of 3 cases of pneumonia which harboured a viral sequencing showing 80% similarity to SARS virus to Wuhan City Health Commission. : Dr. Ai Fen, ER chief in Wuhan Central Hospital, was seriously criticized by her superior at Central hospital for her “making rumors”, she needed to verbally tell all her 200 staff not to disclose anything about this pneumonia. She was also told she can not use Wechat or text but only by face to face or phone call. Dr. Ai raised the issue of “human to human transmission” and she received no response. CCTV13 aired the news that eight people in Wuhan were punished by “making and spreading rumors”.
No evidence of “human to human transmission”, no infection of medical staff. Chinese National Health Commission published “Document on 3” (or Prohibition on 3rd) on 1/3/2020 to prohibit any organization from publishing information about pathogen detection and test results, asking all organizations to destroy virus samples or transfer to designated institutions. Any organization of individuals that did not follow this policy will be legally punished. Zhang notified Shanghai Health Commission and National Health Commission to warn them that the new virus is in the same origin with SARS and spread from the respiratory tract and recommended disease control measures in public.
One physician in the Pulmonary Medicine department has abnormal findings in his lungs in Wuhan Xinhua hospital . The hospital held an internal meeting which stressed that it was not allowed to leak this information out especially “can not tell the media”. 1/6/2020 A: Wuhan “Two sessions” started. No public media updated the public about the outbreak. 1/6/2020 A:
Chinese National CDC started 2nd degree emergency response internally.
Chinese President Xi asked that the anti-epidemic measures should not affect normal life. direct reporting system to Chinese National CDC and had system confirmation of successful submission.
However, they found that the submission on 1/9/2020 was deleted . Wuhan CDC staff confirmed with Caixin Media that the Health Commission and CDC on district, city and province levels can see submission of cases from local hospitals in the system but district and city level do not have the authorization to delete them. 1/9/2020 In Hong Kong, experts assumed that the epidemic could have “human to human transmission”. 1/10/2020: A: Wuhan “Two sessions“ ended, no information of the epidemic was discussed at the conference. A: Wuhan Health Commission announced its 1st epidemic report. It mentioned that no new cases were identified since 1/3/2020. No evidence for human to human transmission and no medical staff was infected. A: Dr. Wang Guangfa, expert team member for the National Health Commission, said that the outbreak is controllable when interviewed. 1/10/2020 B: Radiologist, Dr. Li at Wuhan Xinhua hospital identified 3 cases from CT reports with ground-glass opacity. Similar cases increase daily with an exponential manner. There were 30 cases on 1/10/2020. Dr. Li believed that situation was severe since he had never seen any virus that grows this fast and multiplied every few days. Dr.Li stopped believing official reports and contacted his peers from other radiology departments, the situations are not optimistic across hospitals. 1/11/2020 B Prof. Zhang Yongzhen's team from the lab of Shanghai Public Health Clinical Center published the genetic sequence of COVID-19 to GISAID and used GISAID 、 virological.org and GenBank to share with the world at 9am on 1/11/2020. Chinese National Health Commission announced that China will share the virus genetic sequence with WHO that evening. 1/11/2020 A : to close down and subject to disciplinary actions , as the consequence of violating the “3rd Document” (or Prohibition on 3rd) issued on 1/3/2020. 1/12/2020 A: Wuhan CCP secretary, Ma Guoqiang stated on CCTV interview on 1/31/2020 that Wuhan had an increase in pneumonia cases on 1/12 and 1/13. Thus Wuhan started to measure passenger temperatures at airports and high-speed train stations. 1/12/2020 A: The reporting for pneumonia cannot be submitted without approval from Hubei Health Commission, thus reporting was artificially stopped from local hospitals for 5 days. 1/14/202 A: Director of Chinese National Health Commission had video conference with provincial directors. 1/15/2020 A: Chinese National Health Commission held video conferences on prevention and control of the epidemic. Exposed internal confidential documents (see below link) revealed that the meeting conveyed five messages : 1). Alarm of the epidemics. 2). Policy is “keep tension internally and keep a relaxed appearance to public”. 3). Prepare for the epidemic. 4). Ensure the strict procedure for diagnosis of first case to be followed, i.e., the first case can only be made by the national level and announced by the province level. 5). Reduce the fatality rate since death would lead to public panic. asked Guangdong CDC to prepare for human to human transmissions. Chief of Zhongnan hospital ICU protested to the expert panel that “the diagnostic criteria were too strict and will omit true patients. ” 1/18/2020 A: Wuhan Health Commission reported 4 new cases. However, it reported no new cases from 1/12-1/17. Multiple hospitals had the same experience of not being able to report during this period. 1/18/2020 B: Wuhan community organized group dinner event - “Ten-thousand families dinner” in which forty-thousand families participated. 1/19/2020 A: Wuhan CDC and government stated to the media that Wuhan novel coronavirus had low infectivity and can be controlled and prevented. 1/19/2020 B : Dr. Li observed in the reading room that “in the beginning there were 2-3 cases daily, 4-5 cases on day 2, 7-8 cases on day 3, there was no obvious growth in the first 3 days. Then it entered an exponential growth phase, about 30 cases on 1/10 then doubled every 3-4 days, 86 cases on 1/18 then above 100 everyday afterwards. 1/20/2020 B: Jinyintan, Hankou and Wuhan Pulmonary hospital became 3 designated hospitals for pneumonia with a total of 800 beds created. Other hospitals provided 1,200 beds, however the 2,000 beds were soon all occupied. A: Dr. Zhong Nanshan confirmed “human – to – human” transmission and infection of health care professionals at the press conference. 1/21/2020
Wuhan Health Commission announced the infection of 15 medical staff.
Chinese National Health Commission reported that there was human to human transmission and infection of medical staff , source of virus and how virus spread was not identified. 1/22/2020 A: Gao Fu, director of Chinese CDC, commented in press conference that the origin of the epidemic was wild animals. 1/22/2020 B: Fever clinic visits for Red Cross hospital reached 1,700 on 1/22/2020 given the majority of hospitals closed their fever clinics on that day . Visits reached 2,400 the day after at that hospital. 1/23/2020 A: Lockdown of Wuhan was announced. Five million Wuhan residents left Wuhan before lockdown. Appendix B.
Table 1. Summary: Evidence of “human to human transmission by 1/1/2020 Hospital Case Dates Action Reference /media reports Xinhua Hospital The case of family of 3 Dec 27 and 28, 2019, in addition to the 4 cases from the Wet Market (total 7) Hospital reported to District CDC 12/27/19; [1] Central Hospital Sequencing result of “Bat SARS like” novel coronavirus reported by Guang Zhou (Vision Medical) from patient A (Dec-18-2019) Admitted on Dec 18, 2019; Sampled on Dec 24, 2019; Sequencing result reported on December 30, 2019 [2] Central Hospital The case of mother-son pair December 29, 2019 [2] Central Hospital Beijing (CapitalBio MedLab) reported sequencing results of patient Chen 2 as “highly suspicious for SARS”. Admitted on December 27, 2019; Reported on December 30, 2019 [3], [4] Xinhua Hospital One physician in Xinhua Hospital reported symptoms. December 30, 2019 Xinhua Hospital This was confirmed on Jan 11, 2020 and she is the 2nd case of medical staff infection in Xinhua Hospital. Central Hospital A patient who was the owner of a family clinic at the Wet Market Jan 1, 2020 [2] Summary of sequencing results By December 30, 2019, samples were taken from no less than 9 patients of “pneumonia of unknown etiology” in Wuhan, including 6 from the Xinhua Hospital. Sequencing results suggested that the pathogen is a SARS-like coronavirus. These results were reported back to hospitals and reported to Health Commission and CDC. [4] Note: [1]. 应述辉 , 毛旭 . 健康 报】张继先:最早发现了这不㇐样的肺炎 . 2020-02-06. http://wjw.hubei.gov.cn/bmdt/ztzl/fkxxgzbdgrfyyq/yxdx/202002/t20200206_2020334.shtml [2]. 杜 玮 中国新 闻周 刊 : 武 汉 市中心医院医 护 人 员 被感染始末 . FEB 17. https://medium.com/coronavirus19/%E4%B8%AD%E5%9B%BD%E6%96%B0%E9%97%BB%E5%91%A8%E5%88%8A-%E6%AD%A6%E6%B1%89%E5%B8%82%E4%B8%AD%E5%BF%83%E5%8C%BB%E9%99%A2%E5%8C%BB%E6%8A%A4%E4%BA%BA%E5%91%98%E8%A2%AB%E6%84%9F%E6%9F%93%E5%A7%8B%E6%9C%AB-106e63008271 [3]. 武 汉肺炎为何大爆发?财新网踢爆 " 最高密令 " http://news.creaders.net/china/2020/02/29/2196390.html [4]. 高昱等 . 新冠病毒基因测序溯源:警报是 何 时拉响的 》《 财 新网》 月 日 . Article deleted. Appendix B
Table 2. Wuhan epidemiological data by 1/1/2020 according to different resources Presenter Nov-17-19 Dec-1-19 Dec-8-19 Dec-31-19 Jan-1-20
Methods
Note
Wuhan Health Commission Frist case as announced on Jan-11-20. 27 Official announcement Huang et al, Lancet 1 41 [1] Epidemiology Working Group for NCIP Epidemic Response, Chinese Center for 104 Extracted from China's Infectious Disease Information System. [2] South China Morning Post First case of COVID-19 confirmed case can be traced back to this day. 27 by Dec-15, 60 by Dec-20, 180 by Dec-27, 2019. 266 381 Internal data from Chinese government [3] Li Q et al 47 “pneumonia of unknown etiology” surveillance mechanism [4] Table 3. Early sequencing of viral genomes by different labs Sequencing lab Patient Hospital Note Vision Medical, ( 广州微 远基因科技有限公司 ) Guang Zhou; Collaborator is Chinese Medical Science Academy Institute of Virology [1] Patient A Wuhan Central Hospital. Admitted on Dec 18, 2019; Sampled on Dec 24, 2019; Sequencing result reported on December 30, 2019 “Bat SARS like” novel coronavirus. Collaborator is Chinese Medical Science Academy Institute of Virology which submitted the sequence to GISAID in the evening on 1/11/20. Beijing (CapitalBio MedLab) [2] Patient Chen 2 Wuhan Central Hospital. Admitted on December 27, 2019; Reported on December 30, 2019 reported sequencing results of as “highly suspicious for SARS”. Shanghai Public Health Clinical Center affiliated to Fudan University [3] Patient Chen 1 Wuhan Central Hospital. Sequencing finished on 1/5/20. First lab submitted COVID-19 sequence to GISAID at 9 am on 1/11/20. Lab was suspended on 1/12/20. Wuhan Institute of Virology, Chinese Science Academy [4] Sampled on December 30, 2019, Jinyintan Hospital Finished viral genome sequencing on 1/2/20; submitted to GISAID on 1/11/20 and made public on 2/4/20. BGI groups [5] 3 positive samples from 30 samples from Wuhan in December, 2019 Multiple hospitals 3 positive samples received on 12/16, 12/29 and 12/30 3 positive cases showing high similarity to SARS (> 80%); SARS testing kit negative; reported to Wuhan Health Commission on 1/1/2020; whole genome sequencing on 1/3/2020. Chinese CDC [6] Finished sequencing on 1/3/20. Received 4 samples from Wuhan on 1/2/2020. Viral genome sequence submitted to GISAID on 1/12/20. References: 新冠(
SARS-II 型病毒)中国疫情 简史(㇐) https://club.6parkbbs.com/nz/index.php?app=forum&act=threadview&tid=212851 新冠(
SARS-II 型病毒)中国疫情 简史(二) https://club.6parkbbs.com/nz/index.php?app=forum&act=threadview&tid=220012 新冠(
SARS-II 型病毒)中国疫情 简史(三) 上 https://club.6parkbbs.com/bolun/index.php?app=forum&act=threadview&tid=15697937 新冠( SARS-II 型病毒)中国疫情 简 史(三)中 https://club.6parkbbs.com/bolun/index.php?app=forum&act=threadview&tid=15699225 新冠( SARS-II 型病毒)中国疫情 简 史(三)下 https://club.6parkbbs.com/bolun/index.php?app=forum&act=threadview&tid=15700586 2). 武 汉疫情时间线 . https://wuhanmemo.com/ 3). 马晓华 责编:刘展 超 . “ 从 “ 未 见明显人传人 ” 到 “ 人 传人 ” ,复 盘武汉疫情二十天 .” 第㇐财经 •2020-01-21 14:45 https://m.yicai.com/news/100476157.html 4). 韩 挺 . 武 汉时间:从专家组抵达到封城的谜之 天 - 经济观察 网 武 汉疫情最早期的几个关键时间点 武汉疫情最早期的几个关键时间点武汉疫情最早期的几个关键时间点