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Clinical characteristics of 2019 novel coronavirus infection in China

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Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.
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Original article
Clinical characteristics of 2019 novel coronavirus infection in China
Wei-jie Guan 1*, Ph.D., Zheng-yi Ni 2*, M.D., Yu Hu 3*, M.D., Wen-hua Liang 1,4*, Ph. D.,
Chun-quan Ou 5*, MSc., Jian-xing He 1,6*, M.D., Lei Liu 7,8*, M.D., Hong Shan 9*, M.D.,
Chun-liang Lei 10*, M.D., David S.C. Hui 11*, M.D., Bin Du 12*, M.D., Lan-juan Li 13*, M.D.,
Guang Zeng 14*, MSc., Kwok-Yung Yuen 15*, Ph.D., Ru-chong Chen 1, M.D., Chun-li Tang 1,
M.D., Tao Wang 1, M.D., Ping-yan Chen 4, M.D., Jie Xiang 2, M.D., Shi-yue Li 1, M.D., Jin-lin
Wang 1, M.D., Zi-jing Liang 16, M.D., Yi-xiang Peng 17, M.D., Li Wei 18, M.D., Yong Liu 19,
M.D., Ya-hua Hu 20, M.D., Peng Peng 21, M.D., Jian-ming Wang 22, M.D., Ji-yang Liu 23, M.D.,
Zhong Chen 24, M.D., Gang Li 25, M.D., Zhi-jian Zheng 26, M.D., Shao-qin Qiu 27, M.D., Jie Luo
28, M.D., Chang-jiang Ye 29, M.D., Shao-yong Zhu 30, M.D., Nan-shan Zhong 1, M.D., on behalf
of China Medical Treatment Expert Group for 2019-nCoV
1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory
Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou
Medical University, Guangzhou Medical University, Guangzhou, China
2. Wuhan Jin-yintan Hospital, Wuhan, Hubei, China
3. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, Hubei 430022, China
4. Department of Thoracic Oncology, The First Affiliated Hospital of Guangzhou Medical
University, Guangzhou, China
5. State Key Laboratory of Organ Failure Research, Department of Biostatistics, Guangdong
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Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern
Medical University, Guangzhou, China
6. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou
Medical University, Guangzhou, China
7. Shenzhen Third People’s Hospital, Shenzhen, China
8. The Second Affiliated Hospital of Southern University of Science and Technology, National
Clinical Research Center for Infectious Diseases, Shenzhen, China
9. The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
10. Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong,
China
11. Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong
SAR, China
12. Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and
Chinese Academy of Medical Sciences, Peking, China
13. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical
Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine,
Zhejiang University, Hangzhou, Zhejiang, China
14. Chinese Center for Disease Control and Prevention, Beijing, China
15. Department of Clinical Microbiology and Infection Control, The University of Hong
Kong-Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China; Department of
Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong
Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty
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of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative
Region, China
16. Department of Emergency Room, The First Affiliated Hospital of Guangzhou Medical University,
Guangzhou 510120, China
17. The Central Hospital of Wuhan, Wuhan, Hubei, China
18. Wuhan No.1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan,
Hubei, China
19. Chengdu Public Health Clinical Medical Center, Chengdu, Sichuan, China
20. Huangshi Central Hospital of Edong Healthcare Group, Affiliated Hospital of Hubei Polytechnic
University, Huangshi, Hubei, China
21. Wuhan Pulmonary Hospital, Wuhan, 430030, Hubei, China
22. Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei
430065, China
23. The First Hospital of Changsha, Changsha 410005, Hunan, China
24. The Third People's Hospital of Hainan Province, Sanya, 572000, Hainan, China
25. Huanggang Central Hospital, Huanggang, Hubei, China
26. Wenling First People's Hospital, Wenling, Zhejiang, China
27. The Third People's Hospital of Yichang, Yichang, 443000, Hubei Province, China
28. Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, China
29. Xiantao First People's Hospital, Xiantao, China
30. The People's Hospital of Huangpi District, Wuhan, China
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* Drs. Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng and Yuen contributed
equally to the article.
Corresponding author: Nan-Shan Zhong. State Key Laboratory of Respiratory Disease, National
Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The
First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou,
Guangdong, China. Tel.: +86-20-83062729; Fax: +86-20-83062729; E-mail: nanshan@vip.163.com
Abstract
Background: Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus
(2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate
the clinical characteristics of these cases.
Methods: We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from
552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020.
Results: The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a
direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with
people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea
is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission,
ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%).
Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase
polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs.
5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were
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admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently
associated with either the admission to intensive care unit, mechanical ventilation, or death in
multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval,
4.06 to 23.67).
Conclusions: The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal
radiologic findings are present among some patients with 2019-nCoV infection. The disease severity
(including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT
manifestations) predict poor clinical outcomes.
Key words: 2019 novel coronavirus; acute respiratory disease; transmission; mortality; risk factor
Abstract: 249 words; main text: 2677 words
Funding: Supported by Ministry of Science and Technology, National Health Commission, National
Natural Science Foundation, Department of Science and Technology of Guangdong Province.
Author’s contribution: W. J. G., J. X. H., W. H. L., C. Q. O., P. Y. C., L. J. L., G. Z., K. Y. Y., B. D.,
and N. S. Z. participated in study design; C. Q. O., P. Y. C., W. J. G., and W. H. L. performed data
analysis; Z. Y. N., L. L., H. S., C. L. L., L. J. L., G. Z., K. Y. Y., B. D., R. C. C., C. L. T., T. W., J. X.,
S. Y. L., J. L. W., Z. J. L., Y. H., Y. X. P., L. W., Y. L., Y. H. H., P. P., J. M. W., J. Y. L., Z. C., G. L., Z.
J. Z., S. Q. Q., J. L., C. J. Y., S. Y. Z., and N. S. Z. recruited patients; W. J. G., J. X. H., W. H. L., D. S.
C. H., and N. S. Z. drafted the manuscript; W. J. G., J. X. H., W. H. L., C. Q. O., Z. Y. N., L. L., H. S.,
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C. L. L., D. S. C. H., L. J. L., G. Z., K. Y. Y., B. D., and N. S. Z. were responsible for study
conception; all authors provided critical review of the manuscript and approved the final draft for
publication.
Conflict of interest: None declared.
Running head: 2019-nCoV in China
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Introduction
In early December 2019, the first pneumonia cases of unknown origins were identified in Wuhan city,
Hubei province, China [1]. High-throughput sequencing has revealed a novel betacoronavirus that is
currently named 2019 novel coronavirus (2019-nCoV) [2], which resembled severe acute respiratory
syndrome coronavirus (SARS-CoV) [3]. The 2019-nCoV is the seventh member of enveloped RNA
coronavirus (subgenus sarbecovirus, Orthocoronavirinae subfamily) [3]. Evidence pointing to the
person-to-person transmission in hospital and family settings has been accumulating [4-8].
The World Health Organization has recently declared the 2019-nCoV a public health emergency
of international concern [9]. As of February 5th, 2020, 24,554 laboratory-confirmed cases have been
documented globally (i.e., the USA, Vietnam, Germany) [5,6,9,10]. 28,018 laboratory-confirmed
cases and 563 death cases in China as of February 6th, 2020 [11]. Despite the rapid spread worldwide,
the clinical characteristics of 2019-nCoV acute respiratory disease (ARD) remain largely unclear. In
two recent studies documenting the clinical manifestations of 41 and 99 patients respectively with
laboratory-confirmed 2019-nCoV ARD who were admitted to Wuhan, the severity of some cases
with 2019-nCoV ARD mimicked that of SARS-CoV [1,12]. Given the rapid spread of 2019-nCoV,
an updated analysis with significantly larger sample sizes by incorporating cases throughout China is
urgently warranted. This will not only identify the defining epidemiological and clinical
characteristics with greater precision, but also unravel the risk factors associated with mortality. Here,
by collecting the data from 1,099 laboratory-confirmed cases, we sought to provide an up-to-date
delineation of the epidemiological and clinical characteristics of patients with 2019-nCoV ARD
throughout mainland China.
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Methods
Data sources
We performed a retrospective study on the clinical characteristics of laboratory-confirmed cases with
2019-nCoV ARD. The initial cases were diagnosed as having ‘pneumonia of unknown etiology’,
based on the clinical manifestations and chest radiology after exclusion of the common bacteria or
viruses associated with community-acquired pneumonia. Suspected cases were identified as having
fever or respiratory symptoms, and a history of exposure to wildlife in Wuhan seafood market, a
travel history or contact with people from Wuhan within 2 weeks [13]. Cases were diagnosed based
on the WHO interim guidance [14]. A confirmed case with 2019-nCoV ARD was defined as a
positive result to high-throughput sequencing or real-time reverse-transcriptase
polymerase-chain-reaction (RT-PCR) assay for nasal and pharyngeal swab specimens [1]. Only the
laboratory-confirmed cases were included the analysis. The incubation period was defined as the
duration from the contact of the transmission source to the onset of symptoms. The study was
approved by the National Health Commission and the institutional board of each participating site.
Written informed consent was waived in light of the urgent need to collect clinical data.
The epidemiological characteristics (including recent exposure history), clinical symptoms and
signs and laboratory findings were extracted from electronic medical records. Radiologic
assessments included chest X-ray or computed tomography. Laboratory assessments consisted of
complete blood count, blood chemistry, coagulation test, liver and renal function, electrolytes,
C-reactive protein, procalcitonin, lactate dehydrogenase and creatine kinase. The severity of
2019-nCoV ARD was defined based on the international guidelines for community-acquired
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pneumonia [15].
The primary composite endpoint was the admission to intensive care unit (ICU), or mechanical
ventilation, or death. Secondary endpoints comprised mortality rate, the time from symptom onset to
the composite endpoint and each of its component. Because clinical observations were still ongoing,
fixed time frame (i.e. within 28 days) was not applied to these endpoints.
All medical records were copied and sent to the data processing center in Guangzhou, under the
coordination of the National Health Commission. A team of experienced respiratory clinicians
reviewed and abstracted the data. Data were entered into a computerized database and cross-checked.
If the core data were missing, requests of clarification were immediately sent to the coordinators who
subsequently contacted the attending clinicians. The definition of exposure to wildlife, acute
respiratory distress syndrome (ARDS), pneumonia, acute kidney failure, acute heart failure and
rhabdomyolysis are provided in the Supplementary Appendix.
Laboratory confirmation
Laboratory confirmation of the 2019-nCoV was achieved through the concerted efforts of the
Chinese Center for Disease Prevention and Control (CDC), the Chinese Academy of Medical
Science, Academy of Military Medical Sciences, and Wuhan Institute of Virology. The RT-PCR
assay was conducted in accordance with the protocol established by the World Health Organization
[16]. Further details are available in the Supplementary Appendix.
Statistical analysis
Continuous variables were expressed as the means and standard deviations or medians and
interquartile ranges (IQR) as appropriate. Categorical variables were summarized as the counts and
percentages in each category. We grouped patients into severe and non-severe 2019-nCoV ARD
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according to the American Thoracic Society guideline on admission [15]. Wilcoxon rank-sum tests
were applied to continuous variables, chi-square tests and Fisher’s exact tests were used for
categorical variables as appropriate. The risk of composite endpoints among hospitalized cases and
the potential risk factors were analyzed using Fine-Gray competing-risk models in which recovery is
a competing risk. The proportional hazard Cox model was used in sensitivity analyses. The candidate
risk factors included an exposure history, greater age, abnormal radiologic and laboratory findings,
and the development of complications. We fitted univariate models with a single candidate variable
once at a time. The statistically significant risk factors, sex, and smoking status were included into
the final models. The sub-distribution hazards ratio (SDHR) along with the 95% confidence interval
(95%CI) were reported. All analyses were conducted with R software version 3.6.2 (R Foundation
for Statistical Computing). Distribution map was plotted using ArcGis version 10.2.2.
Results
Demographic and clinical characteristics
Of all 1,324 patients recruited as of January 29th, 222 (16.8%) had a suspected diagnosis and were
therefore excluded. The core data sets (including clinical outcomes and symptoms) of 3 patients were
lacking due to the incompleteness of original reports, hence this report delineates 1,099 patients with
2019-nCoV ARD from 552 hospitals in 31 provinces/province-level municipalities (Fig. 1).
The demographic and clinical characteristics are shown in Table 1. 2.09% were healthcare
workers. A history of contact with wildlife, recent travel to Wuhan, and contact with people from
Wuhan was documented in 1.18%, 31.30% and 71.80% of patients, respectively. 483 (43.95%)
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patients were local residents of Wuhan. 26.0% of patients outside of Wuhan did not have a recent
travel to Wuhan or contact with people from Wuhan. The median incubation period was 3.0 days
(range, 0 to 24.0).
The median age was 47.0 years (IQR, 35.0 to 58.0), and 41.9% were females. 2019-nCoV ARD
was diagnosed throughout the whole spectrum of age. 0.9% of patients were aged below 15 years.
Fever (87.9%) and cough (67.7%) were the most common symptoms, whereas diarrhea (3.7%) and
vomiting (5.0%) were rare. 25.2% of patients had at least one underlying disorder (i.e., hypertension,
chronic obstructive pulmonary disease). On admission, 926 and 173 patients were categorized into
non-severe and severe subgroups, respectively. The age differed significantly between the two groups
(mean difference, 7.0, 95%CI, 4.4 to 9.6). Moreover, any underlying disorder was significantly more
common in severe cases as compared with non-severe cases (38.2% vs. 22.5%, P<0.001). There
were, however, no marked differences in the exposure history between the two groups (all P>0.05).
Radiologic and laboratory findings at presentation
Table 2 shows the radiologic and laboratory findings on admission. Of 840 patients who underwent
chest computed tomography on admission, 76.4% manifested as pneumonia. The most common
patterns on chest computed tomography were ground-glass opacity (50.0%) and bilateral patchy
shadowing (46.0%). Figure E1 in the Supplementary Appendix demonstrates the representative
radiologic findings of two patients with non-severe 2019-nCoV ARD and another two patients with
severe 2019-nCoV ARD. Despite these predominant manifestations, 221 out of 926 (23.87%) in
severe cases compared with 9 out of 173 non-severe cases (5.20%) who had no abnormal
radiological findings were diagnosed by symptoms plus RT-PCR positive findings (P<0.001). Severe
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cases yielded more prominent radiologic abnormalities on chest X-ray and computed tomography
than non-severe cases (all P<0.05).
On admission, 82.1% and 36.2% of patients had lymphopenia and thrombocytopenia,
respectively. Overall, leukopenia was observed in 33.7% of patients. Most patients demonstrated
elevated levels of C-reactive protein, but elevated levels of alanine aminotransferase, aspartate
aminotransferase, creatine kinase and D-dimer were less common. Severe cases had more prominent
laboratory abnormalities (i.e., leukopenia, lymphopenia, thrombocytopenia, elevated C-reactive
protein levels) as compared with non-severe cases (all P<0.05).
Treatment and complications
Overall, oxygen therapy, mechanical ventilation, intravenous antibiotics and oseltamivir therapy
were initiated in 38.0%, 6.1%, 57.5% and 35.8% of patients, respectively. All these therapies were
initiated in significantly higher percentages of severe cases (all P<0.05). Significantly more severe
cases received mechanical ventilation (non-invasive: 32.37% vs. 0%, P<0.001; invasive: 13.87% vs.
0%, P<0.001) as compared with non-severe cases. Systemic corticosteroid was given to 18.6% of
cases and more so in the severe group than the non-severe patients (44.5% vs 13.7%, p<0.001).
Moreover, extracorporeal membrane oxygenation was adopted in 5 severe cases but none in
non-severe cases (P<0.001).
During hospital admission, the most common complication was pneumonia (79.1%), followed by
ARDS (3.37%) and shock (1.00%). Severe cases yielded significantly higher rates of any
complication as compared with non-severe cases (94.8% vs. 72.2%, P<0.001) (Table 3).
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Clinical outcomes
The percentages of patients being admitted to the ICU, requiring invasive ventilation and death were
5.00%, 2.18% and 1.36%, respectively. This corresponded to 67 (6.10%) of patients having reached
to the composite endpoint (Table 3).
Results of the univariate competing risk model are shown in Table E1 in Supplementary
Appendix. Severe pneumonia cases (SDHR, 9.803; 95%CI, 4.06 to 23.67), leukocyte count greater
than 4,000/mm3 (SDHR, 4.01; 95%CI, 1.53 to 10.55) and interstitial abnormality on chest X-ray
(SDHR, 4.31; 95%CI, 1.73 to 10.75) were associated with the composite endpoint (Fig. 2, see Ta ble
E2 in Supplementary Appendix). Sensitivity analyses are shown in Figure E2 in Supplementary
Appendix.
Discussion
This study has shown that fever occurred in only 43.8% of patients with 2019-nCoV ARD on
presentation but developed in 87.9% following hospitalization. Severe pneumonia occurred in 15.7%
of cases. No radiologic abnormality was noted on initial presentation in 23.9% and 5.2% of severe
and non-severe cases respectively while diarrhea was uncommon. The median incubation period of
2019-nCoV ARD was 3.0 days and it had a relatively lower fatality rate than SARS-CoV and
MERS-CoV. Disease severity independently predicted the composite endpoint.
Our study provided further evidence of human-to-human transmission. Around only 1% of
patients had a direct contact with wildlife, while more than three quarters were local residents of
Wuhan, or had contacted with people from Wuhan. Most cases were recruited after January 1st, 2020.
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These findings echoed the latest reports, including the outbreak of a family cluster [4], transmission
from an asymptomatic individual [6] and the three-phase outbreak patterns [8]. Our study cannot
preclude the presence of ‘super-spreaders’. The median incubation period was shorter than a recent
report of 425 patients (3.0 days vs. 5.2 days) [8]. Our findings have provided evidence from a much
larger sample size to guide the duration of quarantine for close contacts.
Importantly, the routes of transmission might have contributed considerably to the rapid spread
of 2019-nCoV. Conventional routes of transmission of SARS-CoV, MERS-CoV and highly
pathogenic influenza consisted of the respiratory droplets and direct contact [17-19]. According to
our latest pilot experiment, 4 out of 62 stool specimens (6.5%) tested positive to 2019-nCoV, and
another four patients in a separate cohort who tested positive to rectal swabs had the 2019-nCoV
being detected in the gastrointestinal tract, saliva or urine (see Tables E3-E4 in Supplementary
Appendix). In a case with severe peptic ulcer after symptom onset, 2019-nCoV was directly detected
in the esophageal erosion and bleeding site (Hong Shan and Jin-cun Zhao, personal communication).
Collectively, fomite transmission might have played a role in the rapid transmission of 2019-nCoV,
and hence hygiene protection should take into account the transmission via gastrointestinal secretions.
These findings will, by integrating systemic protection measures, curb the rapid spread worldwide.
We have adopted the term 2019-nCoV ARD which has incorporated the laboratory-confirmed
symptomatic cases without apparent radiologic manifestations. Pneumonia was not mandatory for
inclusion. 20.9% patients have isolated 2019-nCoV infection before or without the development of
viral pneumonia. Our findings advocate shifting the focus to identifying and managing patients at an
earlier stage, before disease progression.
In concert of recent publications [1,8,12], the clinical characteristics of 2019-nCoV ARD
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mimicked those of SARS-CoV. Fever and cough were the dominant symptoms whereas
gastrointestinal symptoms were rare, suggesting the difference in viral tropism as compared with
SARS-CoV, MERS-CoV and influenza [20-22]. Notably, fever occurred in only 43.8% of patients on
initial presentation and developed in 87.9% following hospitalization. Absence of fever in
2019-nCoV ARD is more frequent than in SARS-CoV (1%) and MERS-CoV infection (2%) [19] and
such patients may be missed if the surveillance case definition focused heavily on fever detection
[14]. Consistent with two recent reports [1,12], lymphopenia was common and, in some cases, severe.
However, based on a larger sample size and cases recruited throughout China, we found a markedly
lower case fatality rate (1.4%) as compared with that reportedly recently [1,12]. The fatality rate was
lower (0.88%) when incorporating additional pilot data from Guangdong province (N=603) where
effective prevention has been undertaken (unpublished data). Our findings were consistent with the
national official statistics, reporting the mortality of 2.01% in China out of 28,018 cases as of
February 6th, 2020 [11,23]. Early isolation, early diagnosis and early management might have
collectively contributed to the marked reduction in mortality in Guangdong. Furthermore, dilution of
health workforce as a result of central management (i.e., Wuhan JinYinTan Hospital) might have led
to increased mortality rate. These findings will inform the mass public, clinicians and policy makers
the true transmissability of 2019-nCoV which has resulted in a major social panic.
Our study has stratified patients with 2019-nCoV ARD based on the severity on admission
according to international guidelines [15]. Severe cases had significantly higher risk of reaching the
composite endpoint. The risk factors indicated the importance of taking into account the disease
severity, laboratory findings, chest imaging findings in practice. The applicability of MuLBSTA
score, an early warning model for predicting mortality in viral pneumonia, warrants further
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validation [25].
Despite the markedly high phylogenetic homogeneity as compared with SARS-CoV, there are
some clinical characteristics that differentiated 2019-nCoV from SARS-CoV, MERS-CoV, and
seasonal influenza which have been more common in respiratory out-patient clinics and wards.
Table E5 in Supplementary Appendix highlights the defining characteristics of these viruses,
enabling clinicians to differentiate these diagnoses.
Our study has some notable limitations. First, some cases had incomplete documentation of the
exposure history, symptoms and laboratory testing given the variation in the structure of electronic
database among different participating site and the urgent timeline for data extraction. Some cases
were diagnosed in out-patient settings where medical information was briefly documented and
incomplete laboratory testing was applied. There was a shortage of infrastructure and training of
medical staff in non-specialty hospitals, which has been aggravated by the burn-out of local medical
staff in milieu of a surge of cases. Second, because many patients still remained in the hospital, we
did not compare the 28-day rate of the composite endpoint. To mitigate the potential bias, we have
applied the competing-risk model for analysis. Third, we might have missed asymptomatic or mild
cases managed at home, and hence our cohort might represent the more severe end of 2019-nCoV
ARD. However, there were a minority of patients who had no apparent radiologic manifestations,
suggesting that we had included patients at the early stage of disease. Last, we took reference on the
existing international guideline to define the severity of 2019-nCoV because of its global recognition
[15].
In summary, 2019-nCoV elicits a rapid spread of outbreak with human-to-human transmission,
with a median incubation period of 3 days and a relatively low fatality rate. Absence of fever and
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radiologic abnormality occurs in a substantial proportion of patients on initial presentation while
diarrhea is uncommon. The disease severity is an independent predictor of poor outcome. Stringent
and timely epidemiological measures are crucial to curb the rapid spread. Ongoing efforts are needed
to explore for an effective therapy (i.e., protease inhibitors, remdesivir, interferon) for this
emerging acute respiratory infection.
Acknowledgment: We thank the hospital staff (see Supplementary Appendix for a full list of the
staff) for their efforts in recruiting patients. We are indebted to the coordination of Drs. Zong-jiu
Zhang, Ya-hui Jiao, Bin Du, Xin-qiang Gao and Tao Wei (National Health Commission), Yu-fei
Duan and Zhi-ling Zhao (Health Commission of Guangdong Province), Yi-min Li, Zi-jing Liang,
Nuo-fu Zhang, Shi-yue Li, Qing-hui Huang, Wen-xi Huang and Ming Li (Guangzhou Institute of
Respiratory Health) which greatly facilitate the collection of patient’s data. Special thanks are given
to the statistical team members Prof. Zheng Chen, Drs. Dong Han, Li Li, Zheng Chen, Zhi-ying Zhan,
Jin-jian Chen, Li-jun Xu, Xiao-han Xu (State Key Laboratory of Organ Failure Research,
Department of Biostatistics, Guangdong Provincial Key Laboratory of Tropical Disease Research,
School of Public Health, Southern Medical University). We also thank Li-qiang Wang, Wei-peng Cai,
Zi-sheng Chen, Chang-xing Ou, Xiao-min Peng, Si-ni Cui, Yuan Wang, Mou Zeng, Xin Hao, Qi-hua
He, Jing-pei Li, Xu-kai Li, Wei Wang, Li-min Ou, Ya-lei Zhang, Jing-wei Liu, Xin-guo Xiong,
Wei-juna Shi, San-mei Yu, Run-dong Qin, Si-yang Yao, Bo-meng Zhang, Xiao-hong Xie, Zhan-hong
Xie, Wan-di Wang, Xiao-xian Zhang, Hui-yin Xu, Zi-qing Zhou, Ying Jiang, Ni Liu, Jing-jing Yuan,
Zheng Zhu, Jie-xia Zhang, Hong-hao Li, Wei-hua Huang, Lu-lin Wang, Jie-ying Li, Li-fen Gao,
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Jia-bo Gao, Cai-chen Li, Xue-wei Chen, Jia-bo Gao, Ming-shan Xue, Shou-xie Huang, Jia-man Tang,
Wei-li Gu, Jin-lin Wang (Guangzhou Institute of Respiratory Health) for their dedication to data
entry and verification.
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Tabl es Table 1. Clinical characteristics of 1,099 patients with 2019-nCoV ARD
Clinical characteristics, symptoms or signs All patients
(n=1099)
Disease severity Composite endpoint
Non-severe
(n=926)
Severe
(n=173) P value Yes
(n=67)
No
(n=1032) P value
Age, Median (range) – yrs 47.0 (35.0– 58.0) 45.0 (34.0– 57.0)
52.0 (40.0– 65.0) <0.001 63.0 (53.0–71.0) 46.0 (35.0–57.0) <0.001
Age groups – No., %
0-14 yrs 9/1011 (0.9) 8/848 (0.9) 1/163 (0.6) <0.001 0/65 (0.0) 9/946 (1.0) <0.001
15-49 yrs 557/1011 (55.1) 490/848 (57.8) 67/163 (41.1) - 12/65 (18.5) 545/946 (57.6) -
50-64 yrs 292/1011 (28.9) 241/848 (28.4) 51/163 (31.3) - 21/65 (32.3) 271/946 (28.6) -
65 yrs 153/1011 (15.1) 109/848 (12.9) 44/163 (27.0) - 32/65 (49.2) 121/946 (12.8) -
Female sex – No.,% 459/1099 (41.8) 386/926 (41.7) 73/173 (42.2) 0.967 22/67 (32.8) 437/1032 (42.3) 0.161
Smoking history – No., %
Never smokers 927/1085 (85.4) 793/913 (86.9) 134/172 (77.9) <0.001 44/66 (66.7) 883/1019 (86.7) <0.001
Ex-smokers 21/1085 (1.9) 12/913 (1.3) 9/172 (5.2) - 5/66 (7.6) 16/1019 (1.6) -
Current smokers 137/1085 (12.6) 108/913 (11.8) 29/172 (16.9) - 17/66 (25.8) 120/1019 (11.8) -
Exposure to source of transmission within 14 days – No.,%
Local residents of Wuhan 483/1099 (43.9) 400/926 (43.2) 83/173 (48.0) 0.280 39/67 (58.2) 444/1032 (43.0) 0.021
Wildlife 13/1099 (1.2) 10/926 (1.1) 3/173 (1.7) 0.443 1/67 (1.5) 12/1032 (1.2) 0.560
Non local residents: Recently been to Wuhan 193/616 (31.3) 166/526 (31.6) 27/90 (30.0) 0.864 10/28 (35.7) 183/588 (31.1) 0.762
Non local residents: Contacted with people from Wuhan 442/616 (71.8) 376/526 (71.5) 66/90 (73.3) 0.815 19/28 (67.9) 423/588 (71.9) 0.800
Hospitalization – No., % 905/1099 (82.3) 768/926 (82.9) 137/173 (79.2) 0.281 48/67 (71.6) 857/1032 (83.0) 0.027
Incubation period – days
Median (range) 3.0 (0.0–24.0) 3.0 (0.0–24.0) 2.0 (0.0–24.0) 0.951 1.0 (0.0–24.0) 3.0 (0.0–24.0) 0.127
Symptoms and signs
Respiratory symptoms – No., % - - - - - - -
Fever on admission 473/1099 (43.1) 391/926 (42.2) 82/173 (47.4) 0.239 24/67 (35.8) 449/1032 (43.5) 0.270
Temperature on admission ( ) 37.3 (36.7– 38.0) 37.3 (36.7– 38.0)
37.4 (36.7– 38.1)
0.853 36.8 (36.3– 37.8)
37.3 (36.7– 38.0) 0.013
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<37.5 608/1081 (56.2) 519/910 (57.0) 89/171 (52.0) 0.139 42/66 (63.6) 566/1015 (55.8) 0.351
37.5-38.0 238/1081 (22.0) 201/910 (22.1) 37/171 (21.6) - 10/66 (15.2) 228/1015 (22.5) -
38.1-39.0 197/1081 (18.2) 160/910 (17.6) 37/171 (21.6) - 11/66 (16.7) 186/1015 (18.3) -
> 39.0 38/1081 (3.5) 30/910 (3.3) 8/171 (4.7) - 3/66 (4.5) 35/1015 (3.4) -
Fever during hospital admission 966/1099 (87.9) 808/926 (87.3) 158/173 (91.3) 0.167 58/67 (86.6) 908/1032 (88.0) 0.880
Highest temperature during hospital admission ( ) 38.3 (37.8– 38.9) 38.3 (37.8– 38.9) 38.5 (38.0– 39.0) 0.003 38.5 (38.0– 39.0) 38.3 (37.8– 38.9) 0.208
<37.5 92/926 (9.9) 79/774 (10.2) 13/152 (8.6) 0.008 3/54 (5.6) 89/872 (10.2) 0.565
37.5-38.0 286/926 (30.9) 251/774 (32.4) 35/152 (23.0) - 20/54 (37.0) 266/872 (30.5) -
38.1-39.0 434/926 (46.9) 356/774 (46.0) 78/152 (51.3) - 21/54 (38.9) 413/872 (47.4) -
> 39.0 114/926 (12.3) 88/774 (11.4) 26/152 (17.1) - 10/54 (18.5) 104/872 (11.9) -
Conjunctival congestion 9/1099 (0.8) 5/926 (0.5) 4/173 (2.3) 0.039 0/67 (0.0) 9/1032 (0.9) 1.000
Nasal congestion 53/1099 (4.8) 47/926 (5.1) 6/173 (3.5) 0.476 2/67 (3.0) 51/1032 (4.9) 0.766
Headache 150/1099 (13.6) 124/926 (13.4) 26/173 (15.0) 0.649 8/67 (11.9) 142/1032 (13.8) 0.813
Cough 744/1099 (67.7) 622/926 (67.2) 122/173 (70.5) 0.438 46/67 (68.7) 698/1032 (67.6) 0.969
Sore throat 153/1099 (13.9) 130/926 (14.0) 23/173 (13.3) 0.889 6/67 (9.0) 147/1032 (14.2) 0.303
Sputum production 367/1099 (33.4) 306/926 (33.0) 61/173 (35.3) 0.632 20/67 (29.9) 347/1032 (33.6) 0.616
Fatigue 419/1099 (38.1) 350/926 (37.8) 69/173 (39.9) 0.665 22/67 (32.8) 397/1032 (38.5) 0.429
Hemoptysis 10/1099 (0.9) 6/926 (0.6) 4/173 (2.3) 0.057 2/67 (3.0) 8/1032 (0.8) 0.120
Shortness of breath 204/1099 (18.6) 139/926 (15.0) 65/173 (37.6) <0.001 36/67 (53.7) 168/1032 (16.3) <0.001
Nausea or vomiting 55/1099 (5.0) 43/926 (4.6) 12/173 (6.9) 0.280 3/67 (4.5) 52/1032 (5.0) 1.000
Diarrhea 41/1099 (3.7) 31/926 (3.3) 10/173 (5.8) 0.183 4/67 (6.0) 37/1032 (3.6) 0.309
Mylgia or arthralgia 163/1099 (14.8) 133/926 (14.4) 30/173 (17.3) 0.371 6/67 (9.0) 157/1032 (15.2) 0.223
Chill 125/1099 (11.4) 99/926 (10.7) 26/173 (15.0) 0.129 8/67 (11.9) 117/1032 (11.3) 1.000
Signs – No., % - - - - - - -
Throat congestion 19/1099 (1.7) 17/926 (1.8) 2/173 (1.2) 0.754 0/67 (0.0) 19/1032 (1.8) 0.624
Tonsil swelling 23/1099 (2.1) 17/926 (1.8) 6/173 (3.5) 0.240 1/67 (1.5) 22/1032 (2.1) 1.000
Enlargement of lymph nodes 2/1099 (0.2) 1/926 (0.1) 1/173 (0.6) 0.290 1/67 (1.5) 1/1032 (0.1) 0.118
Rash 2/1099 (0.2) 0/926 (0.0) 2/173 (1.2) 0.025 0/67 (0.0) 2/1032 (0.2) 1.000
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Coexisting disorders – No., % - - - - - - -
Any 255/1099 (23.2) 190/926 (20.5) 65/173 (37.6) <0.001 39/67 (58.2) 216/1032 (20.9) <0.001
Chronic obstructive pulmonary disease 12/1099 (1.1) 6/926 (0.6) 6/173 (3.5) 0.006 7/67 (10.4) 5/1032 (0.5) <0.001
Diabetes 81/1099 (7.4) 53/926 (5.7) 28/173 (16.2) <0.001 18/67 (26.9) 63/1032 (6.1) <0.001
Hypertension 164/1099 (14.9) 123/926 (13.3) 41/173 (23.7) <0.001 24/67 (35.8) 140/1032 (13.6) <0.001
Coronary heart disease 27/1099 (2.5) 17/926 (1.8) 10/173 (5.8) 0.005 6/67 (9.0) 21/1032 (2.0) 0.004
Cerebrovascular diseases 15/1099 (1.4) 11/926 (1.2) 4/173 (2.3) 0.275 4/67 (6.0) 11/1032 (1.1) 0.010
Hepatitis B infection * 23/1099 (2.1) 22/926 (2.4) 1/173 (0.6) 0.157 1/67 (1.5) 22/1032 (2.1) 1.000
Cancer † 10/1099 (0.9) 7/926 (0.8) 3/173 (1.7) 0.199 1/67 (1.5) 9/1032 (0.9) 0.468
Chronic renal diseases 8/1099 (0.7) 5/926 (0.5) 3/173 (1.7) 0.117 2/67 (3.0) 6/1032 (0.6) 0.081
Immunodeficiency 2/1099 (0.2) 2/926 (0.2) 0/173 (0.0) 1.000 0/67 (0.0) 2/1032 (0.2) 1.000
Data are presented as medians (interquartile ranges, IQR) and n/N (%).
* Hepatitis B infection denoted hepatitis B surface antigen tested positive, with or without elevated alanine or aspartate aminotransferase levels.
† Cancers referred to any malignancy. All cases were stable disease.
P values denoted the comparison between non-severe cases and severe cases.
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Table 2. Radiographic and laboratory findings of 1,099 patients with 2019-nCoV ARD
Radiologic and laboratory findings All patients
(n=1099)
Disease severity Composite endpoint
Non-severe
(n=926)
Severe
(n=173) P value Yes
(n=67)
No
(n=1032)
P
value
Radiologic findings
Abnormalities on chest X-ray – No./total No. (%) 162/1099 (14.7) 116/926 (12.5) 46/173 (26.6) <0.001 30/67 (44.8) 132/1032 (12.8) <0.001
Ground-glass opacity 55/1099 (5.0) 37/926 (4.0) 18/173 (10.4) <0.001 9/67 (13.4) 46/1032 (4.5) 0.005
Local patchy shadowing 77/1099 (7.0) 56/926 (6.0) 21/173 (12.1) 0.007 13/67 (19.4) 64/1032 (6.2) <0.001
Bilateral patchy shadowing 100/1099 (9.1) 65/926 (7.0) 35/173 (20.2) <0.001 27/67 (40.3) 73/1032 (7.1) <0.001
Interstitial abnormalities 12/1099 (1.1) 7/926 (0.8) 5/173 (2.9) 0.028 6/67 (9.0) 6/1032 (0.6) <0.001
Abnormalities on chest CT – No./total No. (%) 840/1099 (76.4) 682/926 (73.7) 158/173 (91.3) <0.001 50/67 (74.6) 790/1032 (76.6) 0.833
Ground-glass opacity 550/1099 (50.0) 449/926 (48.5) 101/173 (58.4) 0.021 30/67 (44.8) 520/1032 (50.4) 0.445
Local patchy shadowing 409/1099 (37.2) 317/926 (34.2) 92/173 (53.2) <0.001 22/67 (32.8) 387/1032 (37.5) 0.525
Bilateral patchy shadowing 505/1099 (46.0) 368/926 (39.7) 137/173 (79.2) <0.001 40/67 (59.7) 465/1032 (45.1) 0.028
Interstitial abnormalities 143/1099 (13.0) 99/926 (10.7) 44/173 (25.4) <0.001 15/67 (22.4) 128/1032 (12.4) 0.030
Laboratory findings
Median PaO2: FiO2 (interquartile range) 3.9 (2.9–4.7) 3.9 (2.9–4.5) 4.0 (2.8–5.2) 0.386 2.9 (2.2– 5.4) 4.0 (3.1– 4.6) 0.150
Blood leukocyte count 4.7 (3.5– 6.0) 4.9 (3.8–6.0) 3.7 (3.0–6.2) <0.001 6.1 (4.911.1) 4.7 (3.5– 5.9) <0.001
>10 * 10^9/L 58/978 (5.9) 39/811 (4.8) 19/167 (11.4) 0.002 15/58 (25.9) 43/920 (4.7) <0.001
<4 * 10^9/L 330/978 (33.7) 228/811 (28.1) 102/167 (61.1) <0.001 8/58 (13.8) 322/920 (35.0) 0.002
Lymphocyte count 1.0 (0.7– 1.3) 1.0 (0.8–1.4) 0.8 (0.6–1.0) <0.001 0.7 (0.6– 0.9) 1.0 (0.7– 1.4) <0.001
< 1.5*10^9/L 731/890 (82.1) 584/736 (79.3) 147/154 (95.5) <0.001 50/54 (92.6) 684/836 (81.5) 0..059
Platelet count 168.0 (132.0–207.0) 172.0 (139.0–212.0) 137.5 (99.0–179.5) <0.001 156.5 (114.2–195.0) 169.0 (133.0–207.0) 0.067
<150 * 10^9/L 315/869 (36.2) 225/713 (31.6) 90/156 (57.7) <0.001 27/58 (46.6) 288/811 (35.5) 0.122
Haemoglobin level – g/dl 134.0 (119.0–148.0) 135.0 (120.0–148.0) 128.0 (111.8–141.0) <0.001 125.0 (105.0–140.0)
134.0 (120.0–148.0) 0.012
C-reactive protein level 10 mg/liter – No./total No. (%) 481/793 (60.7) 371/658 (56.4) 110/135 (81.5) <0.001 41/45 (91.1) 440/748 (58.8) <0.001
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Procalcitonin level 0.5 ng/ml – No./total No. (%) 35/633 (5.5) 19/516 (3.7) 16/117 (13.7) <0.001 12/50 (24.0) 23/583 (3.9) <0.001
Lactose dehydrogenase 250 U/liter – No./total No. (%) 277/675 (41.0) 205/551 (37.2) 72/124 (58.1) <0.001 31/44 (70.5) 246/631 (39.0) <0.001
Aspartate aminotransferase >40 U/liter – No./total No. (%) 168/757 (22.2) 112/615 (18.2) 56/142 (39.4) <0.001 26/52 (50.0) 142/705 (20.1) <0.001
Alanine aminotransferase >40 U/liter – No./total No. (%) 158/741 (21.3) 120/606 (19.8) 38/135 (28.1) 0.043 20/49 (40.8) 138/692 (19.9) 0.001
Total bilirubin 17.1 mol/liter – No./total No. (%) 76/722 (10.5) 59/594 (9.9) 17/128 (13.3) 0.337 10/48 (20.8) 66/674 (9.8) 0.030
Creatinine kinase 200 U/liter – No./total No. (%) 90/657 (13.7) 67/536 (12.5) 23/121 (19.0) 0.083 12/46 (26.1) 78/611 (12.8) 0.021
Creatinine 133 mol/liter – No./total No. (%) 12/752 (1.6) 6/614 (1.0) 6/138 (4.3) 0.012 5/52 (9.6) 7/700 (1.0) <0.001
D-dimer 0.5 mg/liter – No./total No. (%) 260/560 (46.4) 195/451 (43.2) 65/109 (59.6) 0.003 34/49 (69.4) 226/511 (44.2) 0.001
Sodium – mmol/liter 138.2 (136.1–140.3) 138.4 (136.6–140.4)
138.0 (136.0–140.0)
0.090 138.3 (135.0–141.2) 138.2 (136.1–140.2) 0.997
Potassium – mmol/liter 3.8 (3.5– 4.2) 3.9 (3.6–4.2) 3.8 (3.5–4.1) 0.044 3.9 (3.64.1) 3.8 (3.5– 4.2) 0.854
Chloride – mmol/liter 102.9 (99.7–105.6) 102.7 (99.7–105.3) 103.1 (99.8–106.0) 0.206 103.8 (100.8–107.0)
102.8 (99.6–105.3) 0.092
Plus–minus values are means ± SD. Lymphopenia denoted the lymphocyte count of less than 1,500 per cubic millimeter. Thrombocytopenia
denoted the platelet count of less than 150,000 per cubic millimeter. PaO2:FiO2 was defined as the ratio of the partial pressure of arterial oxygen
to the fraction of inspired oxygen.
P values denoted the comparison between mild-moderate cases and severe cases.
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Table 3. Complications, treatment and outcomes of 1,099 patients with 2019-nCoV ARD
Characteristics All patients
(n=1099)
Disease severity Composite endpoint
Non-severe
(n=926)
Severe
(n=173) P value Yes
(n=67)
No
(n=1032) P value
Complications – No., %
Septic shock 11/1099 (1.0) 0/926 (0.0) 11/173 (6.4) <0.001 9/67 (13.4) 2/1032 (0.2) <0.001
Acute respiratory distress syndrome 37/1099 (3.4) 10/926 (1.1) 27/173 (15.6) <0.001 27/67 (40.3) 10/1032 (1.0) <0.001
Acute kidney injury 6/1099 (0.5) 1/926 (0.1) 5/173 (2.9) <0.001 4/67 (6.0) 2/1032 (0.2) <0.001
Disseminated intravascular coagulation 1/1099 (0.1) 0/926 (0.0) 1/173 (0.6) 0.157 1/67 (1.5) 0/1032 (0.0) 0.061
Rhabdomyolysis 1/1099 (0.1) 1/926 (0.1) 0/173 (0.0) 1.000 0/67 (0.0) 1/1032 (0.1) 1.000
Pneumonia 869/1099 (79.1) 705/926 (76.1) 164/173 (94.8) <0.001 59/67 (88.1) 810/1032 (78.5) 0.087
Time from the initial diagnosis to developing pneumonia (days)
Median, interquartile range 0.0 (0.0–2.0) 0.0 (0.0–2.0) 1.0 (0.0–3.0) <0.001 1.0 (0.0–5.0) 0.0 (0.0–2.0) 0.001
Range 0.0 (0.0–60.0) 0.0 (0.0–47.0) 1.0 (0.0–60.0) <0.001 1.0 (0.0–60.0) 0.0 (0.0–47.0) 0.001
Time from symptom onset to developing pneumonia (days)
Median, interquartile range 4.0 (2.0–7.0) 4.0 (2.0–6.0) 5.0 (3.0–8.0) <0.001 5.5 (3.0–10.0) 4.0 (2.0–7.0) 0.015
Range 4.0 (0.0–46.0) 4.0 (0.0–43.0) 5.0 (0.0–46.0) <0.001 5.5 (0.0–46.0) 4.0 (0.0–43.0) 0.015
Supportive treatment – No., %
Administration of intravenous antibiotics – No., % 632/1099 (57.5) 493/926 (53.2) 139/173 (80.3) <0.001 60/67 (89.6) 572/1032 (55.4) <0.001
Administration of oseltamivir – No., % 393/1099 (35.8) 313/926 (33.8) 80/173 (46.2) 0.002 36/67 (53.7) 357/1032 (34.6) 0.002
Administration of antifungal medications – No., % 30/1099 (2.7) 17/926 (1.8) 13/173 (7.5) <0.001 8/67 (11.9) 22/1032 (2.1) <0.001
Administration of systemic corticosteroids – No., % 204/1099 (18.6) 127/926 (13.7) 77/173 (44.5) <0.001 35/67 (52.2) 169/1032 (16.4) <0.001
Maximal daily dose of corticosteroids (mg/kg) 1.5 (0.7–40.0) 1.0 (0.6–40.0) 30.0 (1.0–40.0) 0.014 1.6 (1.0–35.0) 1.5 (0.6–40.0) 0.505
Oxygen therapy – No., % 418/1099 (38.0) 304/926 (32.8) 114/173 (65.9) <0.001 58/67 (86.6) 360/1032 (34.9) <0.001
Mechanical ventilation – No., % 67/1099 (6.1) 0/926 (0.0) 67/173 (38.7) <0.001 40/67 (59.7) 27/1032 (2.6) <0.001
Invasive 24/1099 (2.2) 0/926 (0.0) 24/173 (13.9) <0.001 24/67 (35.8) 0/1032 (0.0) <0.001
Non-invasive 56/1099 (5.1) 0/926 (0.0) 56/173 (32.4) <0.001 29/67 (43.3) 27/1032 (2.6) <0.001
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Use of extracorporeal membrane oxygenation – No., % 5/1099 (0.5) 0/926 (0.0) 5/173 (2.9) <0.001 5/67 (7.5) 0/1032 (0.0) <0.001
Use of continuous renal replacement therapy – No., % 9/1099 (0.8) 0/926 (0.0) 9/173 (5.2) <0.001 8/67 (11.9) 1/1032 (0.1) <0.001
Use of intravenous immunoglobin – No., % 143/1099 (13.0) 86/926 (9.3) 57/173 (32.9) <0.001 27/67 (40.3) 116/1032 (11.2) <0.001
Intensive care unit admission – No., % 55/1099 (5.0) 22/926 (2.4) 33/173 (19.1) <0.001 55/67 (82.1) 0/1032 (0.0) <0.001
Clinical outcomes
Discharge from hospital 55/1099(5.0) 50/926(5.4) 5/173 (2.9) 0.230 1/67(1.5) 54/1032 (5.2) 0.249
Death 15/1099 (1.4) 1/926 (0.1) 14/173 (8.1) <0.001 15/67 (22.4) 0/1032 (0.0) <0.001
Recovered 9/1099 (0.8) 7/926 (0.8) 2/173 (1.2) 0.639 0/67 (0.0) 9/1032 (0.9) 1.000
Staying in hospital 1029/1099 (93.6) 875/926 (94.5) 154/173 (89.0) 0.011 51/67 (76.1) 978/1032 (94.8) <0.001
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Figure legends
Figure 1. Patient recruitment flowchart and the distribution of patients across China
Figure 1-A. Patient recruitment flowchart
Figure 1-B. The distribution of laboratory-confirmed cases throughout China
Shown are the official statistics of all documented laboratory-confirmed cases throughout China
according to the National Health Commission (as of February 4th, 2020).
Figure 2. The risk and the percentage of patients with 2019-nCoV ARD who reached to the
composite endpoint
Figure 2-A. The risk of reaching to the composite endpoint for all patients with 2019-nCoV ARD
Figure 2-B. The risk of reaching to the composite endpoint for non-severe cases
Figure 2-C. The risk of reaching to the composite endpoint for severe cases
Figure 2- D. Shown are the stratification by age, Sex, disease severity, smoking status, underlying
disease, alanine or aspartate aminotransferase levels, blood leukocyte count, blood lymphocyte count,
blood platelet count, ground-glass opacity on chest X-ray on admission, local patchy shadowing on
chest X-ray on admission, diffuse patchy shadowing on chest X-ray on admission, interstitial
abnormality on chest X-ray on admission, interstitial abnormality on chest computed tomography on
admission.
2019-nCoV ARD: 2019 novel coronavirus acute respiratory disease
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Background: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
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In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
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An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
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Background: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.