《内科学》课程教学资源（新冠文献）Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.pdf

Articles www.thelancet.com Vol 395 February 15, 2020 497 Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Chaolin Huang*, Yeming Wang*, Xingwang Li*, Lili Ren*, Jianping Zhao*, Yi Hu*, Li Zhang, Guohui Fan, Jiuyang Xu, Xiaoying Gu, Zhenshun Cheng, Ting Yu, Jiaan Xia, Yuan Wei, Wenjuan Wu, Xuelei Xie, Wen Yin, Hui Li, Min Liu, Yan Xiao, Hong Gao, Li Guo, Jungang Xie, Guangfa Wang, Rongmeng Jiang, Zhancheng Gao, Qi Jin, Jianwei Wang†, Bin Cao† Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission. Copyright © 2020 Elsevier Ltd. All rights reserved. Introduction Coronaviruses are enveloped non-segmented positivesense RNA viruses belonging to the family Coronaviridae and the order Nidovirales and broadly distributed in humans and other mammals.1 Although most human coronavirus infections are mild, the epidemics of the two betacoronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) 2–4 and Middle East respiratory syndrome coronavirus (MERS-CoV),5,6 have caused more than 10 000 cumulative cases in the past two decades, with mortality rates of 10% for SARS-CoV and 37% for MERS-CoV.7,8 The coronaviruses already identified might only be the tip of the iceberg, with potentially more novel and severe zoonotic events to be revealed. In December, 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China, with clinical presentations greatly resembling viral pneumonia.9 Deep sequencing analysis from lower respiratory tract samples indicated a novel coronavirus, which was named 2019 novel coronavirus (2019-nCoV). Thus far, more than 800 confirmed cases, including in health-care workers, have been identified in Wuhan, and several exported cases have been confirmed in other provinces in China, and in Thailand, Japan, South Korea, and the USA.10–13 Lancet 2020; 395: 497–506 Published Online January 24, 2020 https://doi.org/10.1016/ S0140-6736(20)30183-5 This online publication has been corrected. The corrected version first appeared at thelancet.com on January 30, 2020 See Comment pages 469 and 470 *Contributed equally †Joint corresponding authors Jin Yin-tan Hospital, Wuhan, China (Prof C Huang MD, Prof L Zhang MD, T Yu MD, J Xia MD, Y Wei MD, Prof W Wu MD, Prof X Xie MD); Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases (Y Wang MD, G Fan MS, X Gu PhD, H Li MD, Prof B Cao MD), Institute of Clinical Medical Sciences (G Fan, X Gu), and Department of Radiology (M Liu MD), China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China (Y Wang, G Fan, X Gu, H Li, Prof B Cao); Department of Respiratory Medicine, Capital Medical University, Beijing, China (Y Wang, H Li, Prof B Cao); Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China (Prof X Li MD, Prof R Jiang MD); NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology (Prof L Ren PhD, Y Xiao MS, Prof L Guo PhD, Q Jin PhD, Prof J Wang PhD), and Institute of Laboratory Animal Science (Prof H Gao PhD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Tongji Hospital (Prof J Zhao MD, Prof J Xie MD), and Department

Articles 498 www.thelancet.com Vol 395 February 15, 2020 of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan (Y Hu MD, W Yin MD), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Tsinghua University School of Medicine, Beijing, China (J Xu MDc); Department of Respiratory medicine, Zhongnan Hospital of Wuhan University, Wuhan, China (Prof Z Cheng MD); Department of Pulmonary and Critical Care Medicine, Peking University First Hospital, Beijing, China (Prof G Wang MD); Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, China (Prof Z Gao MD); and Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China (Prof B Cao) Correspondence to: Prof Bin Cao, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China caobin_ben@163.com or Prof Jianwei Wang, NHC Key Laboratory of Systems Biology of Pathogens and Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China wangjw28@163.com We aim to describe epidemiological, clinical, laboratory, and radiological characteristics, treatment, and outcomes of patients confirmed to have 2019-nCoV infection, and to compare the clinical features between intensive care unit (ICU) and non-ICU patients. We hope our study findings will inform the global community of the emergence of this novel coronavirus and its clinical features. Methods Patients Following the pneumonia cases of unknown cause reported in Wuhan and considering the shared history of exposure to Huanan seafood market across the patients, an epidemiological alert was released by the local health authority on Dec 31, 2019, and the market was shut down on Jan 1, 2020. Meanwhile, 59 suspected cases with fever and dry cough were transferred to a designated hospital starting from Dec 31, 2019. An expert team of physicians, epidemiologists, virologists, and government officials was soon formed after the alert. Since the cause was unknown at the onset of these emerging infections, the diagnosis of pneumonia of unknown cause in Wuhan was based on clinical characteristics, chest imaging, and the ruling out of common bacterial and viral pathogens that cause pneumonia. Suspected patients were isolated using airborne precautions in the designated hospital, Jin Yintan Hospital (Wuhan, China), and fit-tested N95 masks and airborne precautions for aerosol-generating procedures were taken. This study was approved by the National Health Commission of China and Ethics Commission of Jin Yin-tan Hospital (KY-2020-01.01). Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases. Procedures Local centres for disease control and prevention collected respiratory, blood, and faeces specimens, then shipped them to designated authoritative laboratories to detect the pathogen (NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Beijing, China). A novel coronavirus, which was named 2019-nCoV, was isolated then from lower respiratory tract specimen and a diagnostic test for this virus was developed soon after that.14 Of 59 suspected cases, 41 patients were confirmed to be infected with 2019-nCoV. The presence of 2019-nCoV in respiratory specimens was detected by nextgeneration sequencing or real-time RT-PCR methods. The primers and probe target to envelope gene of CoV were used and the sequences were as follows: forward primer 5′-ACTTCTTTTTCTTGCTTTCGTGGT-3′; reverse primer 5′-GCAGCAGTACGCACACAATC-3′; and the probe 5′CY5-CTAGTTACACTAGCCATCCTTACTGC-3′BHQ1. Conditions for the amplifications were 50°C for 15 min, 95°C for 3 min, followed by 45 cycles of 95°C for 15 s and 60°C for 30 s. Initial investigations included a complete blood count, coagulation profile, and serum biochemical test (including renal and liver function, creatine kinase, lactate dehydrogenase, and electrolytes). Respiratory specimens, including nasal and pharyngeal swabs, bronchoalveolar lavage fluid, sputum, or bronchial aspirates were tested for common viruses, including influenza, avian influenza, respiratory syncytial virus, adenovirus, parainfluenza virus, SARS-CoV and MERS-CoV using real-time RT-PCR assays approved by the China Food and Drug Administration. Routine bacterial and fungal examinations were also performed. Given the emergence of the 2019-nCoV pneumonia cases during the influenza season, antibiotics (orally and intravenously) and oseltamivir (orally 75 mg twice daily) were empirically administered. Corticosteroid therapy Research in context Evidence before this study Human coronaviruses, including hCoV-229E, OC43, NL63, and HKU1, cause mild respiratory diseases. Fatal coronavirus infections that have emerged in the past two decades are severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus. We searched PubMed and the China National Knowledge Infrastructure database for articles published up to Jan 11, 2020, using the keywords “novel coronovirus”, “2019 novel coronavirus”, or “2019-nCoV”. No published work about the human infection caused by the 2019 novel coronavirus (2019-nCoV) could be identified. Added value of this study We report the epidemiological, clinical, laboratory, and radiological characteristics, treatment, and clinical outcomes of 41 laboratory-confirmed cases infected with 2019-nCoV. 27 (66%) of 41 patients had a history of direct exposure to the Huanan seafood market. The median age of patients was 49·0 years (IQR 41·0–58·0), and 13 (32%) patients had underlying disease. All patients had pneumonia. A third of patients were admitted to intensive care units, and six died. High concentrations of cytokines were recorded in plasma of critically ill patients infected with 2019-nCoV. Implications of all the available evidence 2019-nCoV caused clusters of fatal pneumonia with clinical presentation greatly resembling SARS-CoV. Patients infected with 2019-nCoV might develop acute respiratory distress syndrome, have a high likelihood of admission to intensive care, and might die. The cytokine storm could be associated with disease severity. More efforts should be made to know the whole spectrum and pathophysiology of the new disease

Articles www.thelancet.com Vol 395 February 15, 2020 499 (methylprednisolone 40–120 mg per day) was given as a combined regimen if severe community-acquired pneumonia was diagnosed by physicians at the designated hospital. Oxygen support (eg, nasal cannula and invasive mechanical ventilation) was administered to patients according to the severity of hypoxaemia. Repeated tests for 2019-nCoV were done in patients confirmed to have 2019-nCoV infection to show viral clearance before hospital discharge or discontinuation of isolation. Data collection We reviewed clinical charts, nursing records, laboratory findings, and chest x-rays for all patients with laboratoryconfirmed 2019-nCoV infection who were reported by the local health authority. The admission data of these patients was from Dec 16, 2019, to Jan 2, 2020. Epidemiological, clinical, laboratory, and radiological characteristics and treatment and outcomes data were obtained with standardised data collection forms (modified case record form for severe acute respiratory infection clinical characterisation shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium) from electronic medical records. Two researchers also independently reviewed the data collection forms to double check the data collected. To ascertain the epidemiological and symptom data, which were not available from electronic medical records, the researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Cytokine and chemokine measurement To characterise the effect of coronavirus on the production of cytokines or chemokines in the acute phase of the illness, plasma cytokines and chemokines (IL1B, IL1RA, IL2, IL4, IL5, IL6, IL7, IL8 (also known as CXCL8), IL9, IL10, IL12p70, IL13, IL15, IL17A, Eotaxin (also known as CCL11), basic FGF2, GCSF (CSF3), GMCSF (CSF2), IFNγ, IP10 (CXCL10), MCP1 (CCL2), MIP1A (CCL3), MIP1B (CCL4), PDGFB, RANTES (CCL5), TNFα, and VEGFA were measured using Human Cytokine Standard 27-Plex Assays panel and the Bio-Plex 200 system (Bio-Rad, Hercules, CA, USA) for all patients according to the manufacturer’s instructions. The plasma samples from four healthy adults were used as controls for crosscomparison. The median time from being transferred to a designated hospital to the blood sample collection was 4 days (IQR 2–5). Detection of coronavirus in plasma Each 80 µL plasma sample from the patients and contacts was added into 240 µL of Trizol LS (10296028; Thermo Fisher Scientific, Carlsbad, CA, USA) in the Biosafety Level 3 laboratory. Total RNA was extracted by Direct-zol RNA Miniprep kit (R2050; Zymo research, Irvine, CA, USA) according to the manufacturer’s instructions and 50 µL elution was obtained for each sample. 5 µL RNA was used for real-time RT-PCR, which targeted the NP gene using AgPath-ID One-Step RT-PCR Reagent (AM1005; Thermo Fisher Scientific). The final reaction mix concentration of the primers was 500 nM and probe was 200 nM. Real-time RT-PCR was performed using the following conditions: 50°C for 15 min and 95°C for 3 min, 50 cycles of amplification at 95°C for 10 s and 60°C for 45 s. Since we did not perform tests for detecting infectious virus in blood, we avoided the term viraemia and used RNAaemia instead. RNAaemia was defined as a positive result for real-time RT-PCR in the plasma sample. Definitions Acute respiratory distress syndrome (ARDS) and shock were defined according to the interim guidance of WHO For the International Severe Acute Respiratory and Emerging Infection Consortium–WHO case record form for severe acute respiratory infections see https://isaric.tghn.org/protocols/ severe-acute-respiratoryinfection-data-tools/ Figure 1: Date of illness onset and age distribution of patients with laboratory-confirmed 2019-nCoV infection (A) Number of hospital admissions by age group. (B) Distribution of symptom onset date for laboratory-confirmed cases. The Wuhan local health authority issued an epidemiological alert on Dec 30, 2019, and closed the Huanan seafood market 2 days later. 0 <18 18–24 25–49 50–64 ≥65 5 10 15 20 Number of cases Age (years) A General ward Intensive care unit Dec 1, 2019 Dec 10, 2019 Dec 11, 2019 Dec 12, 2019 Dec 13, 2019 Dec 14, 2019 Dec 15, 2019 Dec 16, 2019 Dec 17, 2019 Dec 18, 2019 Dec 19, 2019 Dec 20, 2019 Dec 21, 2019 Dec 22, 2019 Dec 23, 2019 Dec 24, 2019 Dec 25, 2019 Dec 26, 2019 Dec 27, 2019 Dec 28, 2019 Dec 29, 2019 Dec 30, 2019 Dec 31, 2019 Jan 1, 2020 Jan 2, 2020 0 2 4 6 8 Number of cases Onset date B No Yes Huanan seafood market exposure Epidemiological alert Market closed

Articles 500 www.thelancet.com Vol 395 February 15, 2020 for novel coronavirus.9 Hypoxaemia was defined as arterial oxygen tension (PaO₂) over inspiratory oxygen fraction (FIO₂) of less than 300 mm Hg.15 Acute kidney injury was identified and classified on the basis of the highest serum creatinine level or urine output criteria according to the kidney disease improving global outcomes classification.16 Secondary infection was diagnosed if the patients had clinical symptoms or signs of nosocomial pneumonia or bacteraemia, and was combined with a positive culture of a new pathogen from a lower respiratory tract specimen (including the sputum, transtracheal aspirates, or bronchoalveolar lavage fluid, or from blood samples taken ≥48 h after admission).17 Cardiac injury followed the definition used in our previous study in H7N9 patients.18 In brief, cardiac injury was diagnosed if serum levels of cardiac biomarkers (eg, troponin I) were above the 99th percentile upper reference limit, or new abnormalities were shown in electrocardiography and echocardiography. Statistical analysis Continuous variables were expressed as median (IQR) and compared with the Mann-Whitney U test; categorical variables were expressed as number (%) and compared by χ² test or Fisher’s exact test between ICU care and no ICU care groups. Boxplots were drawn to describe plasma cytokine and chemokine concentrations. A two-sided α of less than 0·05 was considered statistically significant. Statistical analyses were done using the SAS software, version 9.4, unless otherwise indicated. Role of the funding source The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Results By Jan 2, 2020, 41 admitted hospital patients were identified as laboratory-confirmed 2019-nCoV infection in Wuhan. 20 [49%]) of the 2019-nCoV-infected patients were aged 25–49 years, and 14 (34%) were aged 50–64 years (figure 1A). The median age of the patients was 49·0 years (IQR 41·0–58·0; table 1). In our cohort of the first 41 patients as of Jan 2, no children or adolescents were infected. Of the 41 patients, 13 (32%) were admitted to the ICU because they required high-flow nasal cannula or higher-level oxygen support measures to correct hypoxaemia. Most of the infected patients were men (30 [73%]); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). 27 (66%) patients had direct exposure to Huanan seafood market (figure 1B). Market exposure was similar between the patients with ICU care (nine [69%]) and those with non-ICU care (18 [64%]). The symptom onset date of the first patient identified was Dec 1, 2019. None of his family members developed fever or any respiratory symptoms. No epidemiological link was found between the first patient and later cases. The first fatal case, who had continuous exposure to the market, was admitted to hospital because of a 7-day history of fever, cough, and dyspnoea. 5 days after illness onset, his wife, a 53-year-old woman who had no known history of exposure to the market, also presented with pneumonia and was hospitalised in the isolation ward. The most common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms All patients (n=41) ICU care (n=13) No ICU care (n=28) p value Characteristics Age, years 49·0 (41·0–58·0) 49·0 (41·0–61·0) 49·0 (41·0–57·5) 0·60 Sex ·· ·· ·· 0·24 Men 30 (73%) 11 (85%) 19 (68%) ·· Women 11 (27%) 2 (15%) 9 (32%) ·· Huanan seafood market exposure 27 (66%) 9 (69%) 18 (64%) 0·75 Current smoking 3 (7%) 0 3 (11%) 0·31 Any comorbidity 13 (32%) 5 (38%) 8 (29%) 0·53 Diabetes 8 (20%) 1 (8%) 7 (25%) 0·16 Hypertension 6 (15%) 2 (15%) 4 (14%) 0·93 Cardiovascular disease 6 (15%) 3 (23%) 3 (11%) 0·32 Chronic obstructive pulmonary disease 1 (2%) 1 (8%) 0 0·14 Malignancy 1 (2%) 0 1 (4%) 0·49 Chronic liver disease 1 (2%) 0 1 (4%) 0·68 Signs and symptoms Fever 40 (98%) 13 (100%) 27 (96%) 0·68 Highest temperature, °C ·· ·· ·· 0·037 <37·3 1 (2%) 0 1 (4%) ·· 37·3–38·0 8 (20%) 3 (23%) 5 (18%) ·· 38·1–39·0 18 (44%) 7 (54%) 11 (39%) ·· >39·0 14 (34%) 3 (23%) 11 (39%) ·· Cough 31 (76%) 11 (85%) 20 (71%) 0·35 Myalgia or fatigue 18 (44%) 7 (54%) 11 (39%) 0·38 Sputum production 11/39 (28%) 5 (38%) 6/26 (23%) 0·32 Headache 3/38 (8%) 0 3/25 (12%) 0·10 Haemoptysis 2/39 (5%) 1 (8%) 1/26 (4%) 0·46 Diarrhoea 1/38 (3%) 0 1/25 (4%) 0·66 Dyspnoea 22/40 (55%) 12 (92%) 10/27 (37%) 0·0010 Days from illness onset to dyspnoea 8·0 (5·0–13·0) 8·0 (6·0–17·0) 6·5 (2·0–10·0) 0·22 Days from first admission to transfer 5·0 (1·0–8·0) 8·0 (5·0–14·0) 1·0 (1·0–6·5) 0·0023 Systolic pressure, mm Hg 125·0 (119·0–135·0) 145·0 (123·0–167·0) 122·0 (118·5–129·5) 0·018 Respiratory rate >24 breaths per min 12 (29%) 8 (62%) 4 (14%) 0·0023 Data are median (IQR), n (%), or n/N (%), where N is the total number of patients with available data. p values comparing ICU care and no ICU care are from χ² test, Fisher’s exact test, or Mann-Whitney U test. 2019-nCoV=2019 novel coronavirus. ICU=intensive care unit. Table 1: Demographics and baseline characteristics of patients infected with 2019-nCoV

Articles www.thelancet.com Vol 395 February 15, 2020 501 were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38; table 1). More than half of patients (22 [55%] of 40) developed dyspnoea. The median duration from illness onset to dyspnoea was 8·0 days (IQR 5·0–13·0). The median time from onset of symptoms to first hospital admission was 7·0 days (4·0–8·0), to shortness of breath was 8·0 days (5·0–13·0), to ARDS was 9·0 days (8·0–14·0), to mechanical ventilation was 10·5 days (7·0–14·0), and to ICU admission was 10·5 days (8·0–17·0; figure 2). The blood counts of patients on admission showed leucopenia (white blood cell count less than 4 × 10⁹/L; ten [25%] of 40 patients) and lymphopenia (lymphocyte count <1·0 × 10⁹/L; 26 [63%] patients; table 2). Prothrombin time and D-dimer level on admission were higher in ICU patients (median prothrombin time 12·2 s [IQR 11·2–13·4]; median D-dimer level 2·4 mg/L [0·6–14·4]) than non-ICU patients (median prothrombin time 10·7 s [9·8–12·1], p=0·012; median D-dimer level 0·5 mg/L [0·3–0·8], p=0·0042). Levels of aspartate aminotransferase were increased in 15 (37%) of 41 patients, including eight (62%) of 13 ICU patients and seven (25%) of 28 non-ICU patients. Hypersensitive troponin I (hs-cTnI) was increased substantially in five patients, in whom the diagnosis of virus-related cardiac injury was made. Most patients had normal serum levels of procalcitonin on admission (procalcitonin <0·1 ng/mL; 27 [69%] patients; table 2). Four ICU patients developed secondary infections. Three of the four patients with secondary infection had procalcitonin greater than 0·5 ng/mL (0·69 ng/mL, 1·46 ng/mL, and 6·48 ng/mL). On admission, abnormalities in chest CT images were detected among all patients. Of the 41 patients, 40 (98%) had bilateral involvement (table 2). The typical findings of chest CT images of ICU patients on admission were bilateral multiple lobular and subsegmental areas of consolidation (figure 3A). The representative chest CT findings of non-ICU patients showed bilateral groundglass opacity and subsegmental areas of consolidation (figure 3B). Later chest CT images showed bilateral ground-glass opacity, whereas the consolidation had been resolved (figure 3C). Initial plasma IL1B, IL1RA, IL7, IL8, IL9, IL10, basic FGF, GCSF, GMCSF, IFNγ, IP10, MCP1, MIP1A, MIP1B, PDGF, TNFα, and VEGF concentrations were higher in both ICU patients and non-ICU patients than in healthy adults (appendix pp 6–7). Plasma levels of IL5, IL12p70, IL15, Eotaxin, and RANTES were similar between healthy adults and patients infected with 2019-nCoV. Further comparison between ICU and non-ICU patients showed that plasma concentrations of IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A, and TNFα were higher in ICU patients than non-ICU patients. All patients had pneumonia. Common complications included ARDS (12 [29%] of 41 patients), followed by RNAaemia (six [15%] patients), acute cardiac injury (five [12%] patients), and secondary infection (four [10%] patients; table 3). Invasive mechanical ventilation was required in four (10%) patients, with two of them (5%) had refractory hypoxaemia and received extracorporeal membrane oxygenation as salvage therapy. All patients were administered with empirical antibiotic treatment, and 38 (93%) patients received antiviral therapy (oseltamivir). Additionally, nine (22%) patients were given systematic corticosteroids. A comparison of clinical features between patients who received and did not receive systematic corticosteroids is in the appendix (pp 1–5). As of Jan 22, 2020, 28 (68%) of 41 patients have been discharged and six (15%) patients have died. Fitness for discharge was based on abatement of fever for at least 10 days, with improvement of chest radiographic evidence and viral clearance in respiratory samples from upper respiratory tract. Discussion We report here a cohort of 41 patients with laboratoryconfirmed 2019-nCoV infection. Patients had serious, sometimes fatal, pneumonia and were admitted to the designated hospital in Wuhan, China, by Jan 2, 2020. Clinical presentations greatly resemble SARS-CoV. Patients with severe illness developed ARDS and required ICU admission and oxygen therapy. The time between hospital admission and ARDS was as short as 2 days. At this stage, the mortality rate is high for 2019-nCoV, because six (15%) of 41 patients in this cohort died. The number of deaths is rising quickly. As of Jan 24, 2020, 835 laboratory-confirmed 2019-nCoV infections were reported in China, with 25 fatal cases. Reports have been released of exported cases in many provinces in China, and in other countries; Figure 2: Timeline of 2019-nCoV cases after onset of illness Onset Admission Dyspnoea Acute respiratory distress syndrome Intensive care unit admission 7 8 9 10·5 Median time Number of cases Days 41 (100%) 41 (100%) 21 (51%) 11 (27%) 16 (39%) See Online for appendix