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Epidemiological and clinical characteristics of 99 Wuhan nCoV cases - Lancet

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includes 8 new outcomes (5 deaths, 3 discharges). 99 case = 41 in first Lancet report + 58 subsequent cases.  Adds to prior outcomes (6 dead, 28 discharged).  CFR for first 41 likely in 20-25% range.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext#tbl1

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Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Published:January 30, 2020DOI:https://doi.org/10.1016/S0140-6736(20)30211-7
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Summary

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.
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Introduction

Since Dec 8, 2019, several cases of pneumonia of unknown aetiology have been reported in Wuhan, Hubei province, China.
,  
,  
 Most patients worked at or lived around the local Huanan seafood wholesale market, where live animals were also on sale. In the early stages of this pneumonia, severe acute respiratory infection symptoms occurred, with some patients rapidly developing acute respiratory distress syndrome (ARDS), acute respiratory failure, and other serious complications. On Jan 7, a novel coronavirus was identified by the Chinese Center for Disease Control and Prevention (CDC) from the throat swab sample of a patient, and was subsequently named 2019-nCoV by WHO.
Coronaviruses can cause multiple system infections in various animals and mainly respiratory tract infections in humans, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
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,  
 Most patients have mild symptoms and good prognosis. So far, a few patients with 2019-nCoV have developed severe pneumonia, pulmonary oedema, ARDS, or multiple organ failure and have died. All costs of 2019-nCoV treatment are covered by medical insurance in China.
At present, information regarding the epidemiology and clinical features of pneumonia caused by 2019-nCoV is scarce.
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,  
 In this study, we did a comprehensive exploration of the epidemiology and clinical features of 99 patients with confirmed 2019-nCoV pneumonia admitted to Jinyintan Hospital, Wuhan, which admitted the first patients with 2019-nCoV to be reported on.
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Methods

 Study design and participants

For this retrospective, single-centre study, we recruited patients from Jan 1 to Jan 20, 2020, at Jinyintan Hospital in Wuhan, China. Jinyintan Hospital is a hospital for adults (ie, aged ≥14 years) specialising in infectious diseases. According to the arrangements put in place by the Chinese Government, adult patients were admitted centrally to the hospital from the whole of Wuhan without selectivity. All patients at Jinyintan Hospital who were diagnosed as having 2019-nCoV pneumonia according to WHO interim guidance were enrolled in this study.
 All the data of included cases have been shared with WHO. The study was approved by Jinyintan Hospital Ethics Committee and written informed consent was obtained from patients involved before enrolment when data were collected retrospectively.
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Research in context

Evidence before this study
We searched PubMed on Jan 25, 2020, for articles that describe the epidemiological and clinical characteristics of the 2019 novel coronavirus (2019-nCoV) in Wuhan, China, using the search terms “novel coronavirus” and “pneumonia” with no language or time restrictions. Previously published research discussed the epidemiological and clinical characteristics of severe acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus, and primary study for the evolution of the novel coronavirus from Wuhan. The only report of clinical features of patients infected with 2019-nCoV was published on Jan 24, 2020, with 41 cases included.
Added value of this study
We have obtained data on 99 patients in Wuhan, China, to further explore the epidemiology and clinical features of 2019-nCoV. This study is, to our knowledge, the largest case series to date of 2019-nCoV infections, with 99 patients who were transferred to Jinyintan Hospital from other hospitals all over Wuhan, and provides further information on the demographic, clinical, epidemiological, and laboratory features of patients. It presents the latest status of 2019-nCoV infection in China and is an extended investigation of the previous report, with 58 extra cases and more details on combined bacterial and fungal infections. In all patients admitted with medical comorbidities of 2019-nCoV, a wide range of clinical manifestations can be seen and are associated with substantial outcomes.
Implications of all the available evidence
The 2019-nCoV infection was of clustering onset, is more likely to affect older men with comorbidities, and could result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. Early identification and timely treatment of critical cases of 2019-nCoV are important. Effective life support and active treatment of complications should be provided to effectively reduce the severity of patients' conditions and prevent the spread of this new coronavirus in China and worldwide.
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Procedures

We obtained epidemiological, demographic, clinical, laboratory, management, and outcome data from patients' medical records. Clinical outcomes were followed up to Jan 25, 2020. If data were missing from the records or clarification was needed, we obtained data by direct communication with attending doctors and other health-care providers. All data were checked by two physicians (XD and YQ).
Laboratory confirmation of 2019-nCoV was done in four different institutions: the Chinese CDC, the Chinese Academy of Medical Science, Academy of Military Medical Sciences, and Wuhan Institute of Virology, Chinese Academy of Sciences. Throat-swab specimens from the upper respiratory tract that were obtained from all patients at admission were maintained in viral-transport medium. 2019-nCoV was confirmed by real-time RT-PCR using the same protocol described previously.
 RT-PCR detection reagents were provided by the four institutions. Other respiratory viruses including influenza A virus (H1N1, H3N2, H7N9), influenza B virus, respiratory syncytial virus, parainfluenza virus, adenovirus, SARS coronavirus (SARS-CoV), and MERS coronavirus (MERS-CoV) were also examined with real-time RT-PCR
Sputum or endotracheal aspirates were obtained at admission for identification of possible causative bacteria or fungi. Additionally, all patients were given chest x-rays or chest CT.

 Outcomes

We describe epidemiological data (ie, short-term [occasional visits] and long-term [worked at or lived near] exposure to Huanan seafood market); demographics; signs and symptoms on admission; comorbidity; laboratory results; co-infection with other respiratory pathogens; chest radiography and CT findings; treatment received for 2019-nCoV; and clinical outcomes.

 Statistical analysis

We present continuous measurements as mean (SD) if they are normally distributed or median (IQR) if they are not, and categorical variables as count (%). For laboratory results, we also assessed whether the measurements were outside the normal range. We used SPSS (version 26.0) for all analyses.

 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.
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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%]).
Figure thumbnail gr1
Figure 1Date of illness onset and age distribution of patients with laboratory-confirmed 2019-nCoV infection
Table 1Demographics and baseline characteristics of patients infected with 2019-nCoV
    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.
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 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).
Figure thumbnail gr2
Figure 2Timeline of 2019-nCoV cases after onset of illness
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.
Table 2Laboratory findings of patients infected with 2019-nCoV on admission to hospital
    All patients (n=41) ICU care (n=13) No ICU care (n=28) p value
White blood cell count, × 109/L 6·2 (4·1–10·5) 11·3 (5·8–12·1) 5·7 (3·1–7·6) 0·011
  <4 10/40 (25%) 1/13 (8%) 9/27 (33%) 0·041
  4–10 18/40 (45%) 5/13 (38%) 13/27 (48%) ..
  >10 12/40 (30%) 7/13 (54%) 5/27 (19%) ..
Neutrophil count, × 109/L 5·0 (3·3–8·9) 10·6 (5·0–11·8) 4·4 (2·0–6·1) 0·00069
Lymphocyte count, × 109/L 0·8 (0·6–1·1) 0·4 (0·2–0·8) 1·0 (0·7–1·1) 0·0041
  <1·0 26/41 (63%) 11/13 (85%) 15/28 (54%) 0·045
  ≥1·0 15/41 (37%) 2/13 (15%) 13/28 (46%) ..
Haemoglobin, g/L 126·0 (118·0–140·0) 122·0 (111·0–128·0) 130·5 (120·0–140·0) 0·20
Platelet count, × 109/L 164·5 (131·5–263·0) 196·0 (165·0–263·0) 149·0 (131·0–263·0) 0·45
  <100 2/40 (5%) 1/13 (8%) 1/27 (4%) 0·45
  ≥100 38/40 (95%) 12/13 (92%) 26/27 (96%) ..
Prothrombin time, s 11·1 (10·1–12·4) 12·2 (11·2–13·4) 10·7 (9·8–12·1) 0·012
Activated partial thromboplastin time, s 27·0 (24·2–34·1) 26·2 (22·5–33·9) 27·7 (24·8–34·1) 0·57
D-dimer, mg/L 0·5 (0·3–1·3) 2·4 (0·6–14·4) 0·5 (0·3–0·8) 0·0042
Albumin, g/L 31·4 (28·9–36·0) 27·9 (26·3–30·9) 34·7 (30·2–36·5) 0·00066
Alanine aminotransferase, U/L 32·0 (21·0–50·0) 49·0 (29·0–115·0) 27·0 (19·5–40·0) 0·038
Aspartate aminotransferase, U/L 34·0 (26·0–48·0) 44·0 (30·0–70·0) 34·0 (24·0–40·5) 0·10
  ≤40 26/41 (63%) 5/13 (38%) 21/28 (75%) 0·025
  >40 15/41 (37%) 8/13 (62%) 7/28 (25%) ..
Total bilirubin, mmol/L 11·7 (9·5–13·9) 14·0 (11·9–32·9) 10·8 (9·4–12·3) 0·011
Potassium, mmol/L 4·2 (3·8–4·8) 4·6 (4·0–5·0) 4·1 (3·8–4·6) 0·27
Sodium, mmol/L 139·0 (137·0–140·0) 138·0 (137·0–139·0) 139·0 (137·5–140·5) 0·26
Creatinine, μmol/L 74·2 (57·5–85·7) 79·0 (53·1–92·7) 73·3 (57·5–84·7) 0·84
  ≤133 37/41 (90%) 11/13 (85%) 26/28 (93%) 0·42
  >133 4/41 (10%) 2/13 (15%) 2/28 (7%) ..
Creatine kinase, U/L 132·5 (62·0–219·0) 132·0 (82·0–493·0) 133·0 (61·0–189·0) 0·31
  ≤185 27/40 (68%) 7/13 (54%) 20/27 (74%) 0·21
  >185 13/40 (33%) 6/13 (46%) 7/27 (26%) ..
Lactate dehydrogenase, U/L 286·0 (242·0–408·0) 400·0 (323·0–578·0) 281·0 (233·0–357·0) 0·0044
  ≤245 11/40 (28%) 1/13 (8%) 10/27 (37%) 0·036
  >245 29/40 (73%) 12/13 (92%) 17/27 (63%) ..
Hypersensitive troponin I, pg/mL 3·4 (1·1–9·1) 3·3 (3·0–163·0) 3·5 (0·7–5·4) 0·075
  >28 (99th percentile) 5/41 (12%) 4/13 (31%) 1/28 (4%) 0·017
Procalcitonin, ng/mL 0·1 (0·1–0·1) 0·1 (0·1–0·4) 0·1 (0·1–0·1) 0·031
  <0·1 27/39 (69%) 6/12 (50%) 21/27 (78%) 0·029
  ≥0·1 to <0·25 7/39 (18%) 3/12 (25%) 4/27 (15%) ..
  ≥0·25 to <0·5 2/39 (5%) 0/12 2/27 (7%) ..
  ≥0·5 3/39 (8%) 3/12 (25%)
0/27 ..
Bilateral involvement of chest radiographs 40/41 (98%) 13/13 (100%) 27/28 (96%) 0·68
Cycle threshold of respiratory tract 32·2 (31·0–34·5) 31·1 (30·0–33·5) 32·2 (31·1–34·7) 0·39
Data are median (IQR) 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, Fisher's exact test, or Mann-Whitney U test. 2019-nCoV=2019 novel coronavirus. ICU=intensive care unit.
* Complicated typical secondary infection during the first hospitalisation.
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 ground-glass 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).
Table 3Treatments and outcomes of patients infected with 2019-nCoV
    All patients (n=41) ICU care (n=13) No ICU care (n=28) p value
Duration from illness onset to first admission 7·0 (4·0–8·0) 7·0 (4·0–8·0) 7·0 (4·0–8·5) 0·87
Complications
  Acute respiratory distress syndrome 12 (29%) 11 (85%) 1 (4%) <0·0001
  RNAaemia 6 (15%) 2 (15%) 4 (14%) 0·93
  Cycle threshold of RNAaemia 35·1 (34·7–35·1) 35·1 (35·1–35·1) 34·8 (34·1–35·4) 0·35
  Acute cardiac injury
5 (12%) 4 (31%) 1 (4%) 0·017
  Acute kidney injury 3 (7%) 3 (23%) 0 0·027
  Secondary infection 4 (10%) 4 (31%) 0 0·0014
  Shock 3 (7%) 3 (23%) 0 0·027
Treatment
  Antiviral therapy 38 (93%) 12 (92%) 26 (93%) 0·46
  Antibiotic therapy 41 (100%) 13 (100%) 28 (100%) NA
  Use of corticosteroid 9 (22%) 6 (46%) 3 (11%) 0·013
Continuous renal replacement therapy 3 (7%) 3 (23%) 0 0·027
Oxygen support .. .. .. <0·0001
  Nasal cannula 27 (66%) 1 (8%) 26 (93%) ..
  Non-invasive ventilation or high-flow nasal cannula 10 (24%) 8 (62%) 2 (7%) ..
  Invasive mechanical ventilation 2 (5%) 2 (15%) 0 ..
  Invasive mechanical ventilation and ECMO 2 (5%) 2 (15%) 0 ..
Prognosis .. .. .. 0·014
  Hospitalisation 7 (17%) 1 (8%) 6 (21%) ..
  Discharge 28 (68%) 7 (54%) 21 (75%) ..
  Death 6 (15%) 5 (38%) 1 (4%) ..
Data are median (IQR) or n (%). p values are comparing ICU care and no ICU care. 2019-nCoV=2019 novel coronavirus. ICU=intensive care unit. NA=not applicable. ECMO=extracorporeal membrane oxygenation.
* Defined as blood levels of hypersensitive troponin I above the 99th percentile upper reference limit (>28 pg/mL) or new abnormalities shown on electrocardiography and echocardiography.
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.
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Discussion

We report here a cohort of 41 patients with laboratory-confirmed 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; some health-care workers have also been infected in Wuhan. Taken together, evidence so far indicates human transmission for 2019-nCoV. We are concerned that 2019-nCoV could have acquired the ability for efficient human transmission.
 Airborne precautions, such as a fit-tested N95 respirator, and other personal protective equipment are strongly recommended. To prevent further spread of the disease in health-care settings that are caring for patients infected with 2019-nCoV, onset of fever and respiratory symptoms should be closely monitored among health-care workers. Testing of respiratory specimens should be done immediately once a diagnosis is suspected. Serum antibodies should be tested among health-care workers before and after their exposure to 2019-nCoV for identification of asymptomatic infections.
Similarities of clinical features between 2019-nCoV and previous betacoronavirus infections have been noted. In this cohort, most patients presented with fever, dry cough, dyspnoea, and bilateral ground-glass opacities on chest CT scans. These features of 2019-nCoV infection bear some resemblance to SARS-CoV and MERS-CoV infections.
,  
 However, few patients with 2019-nCoV infection had prominent upper respiratory tract signs and symptoms (eg, rhinorrhoea, sneezing, or sore throat), indicating that the target cells might be located in the lower airway. Furthermore, 2019-nCoV patients rarely developed intestinal signs and symptoms (eg, diarrhoea), whereas about 20–25% of patients with MERS-CoV or SARS-CoV infection had diarrhoea.
 Faecal and urine samples should be tested to exclude a potential alternative route of transmission that is unknown at this stage.
The pathophysiology of unusually high pathogenicity for SARS-CoV or MERS-CoV has not been completely understood. Early studies have shown that increased amounts of proinflammatory cytokines in serum (eg, IL1B, IL6, IL12, IFNγ, IP10, and MCP1) were associated with pulmonary inflammation and extensive lung damage in SARS patients.
 MERS-CoV infection was also reported to induce increased concentrations of proinflammatory cytokines (IFNγ, TNFα, IL15, and IL17).
 We noted that patients infected with 2019-nCoV also had high amounts of IL1B, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (Th1) cell responses. Moreover, patients requiring ICU admission had higher concentrations of GCSF, IP10, MCP1, MIP1A, and TNFα than did those not requiring ICU admission, suggesting that the cytokine storm was associated with disease severity. However, 2019-nCoV infection also initiated increased secretion of T-helper-2 (Th2) cytokines (eg, IL4 and IL10) that suppress inflammation, which differs from SARS-CoV infection.
 Further studies are necessary to characterise the Th1 and Th2 responses in 2019-nCoV infection and to elucidate the pathogenesis. Autopsy or biopsy studies would be the key to understand the disease.
In view of the high amount of cytokines induced by SARS-CoV,
,  
 MERS-CoV,
,  
 and 2019-nCoV infections, corticosteroids were used frequently for treatment of patients with severe illness, for possible benefit by reducing inflammatory-induced lung injury. However, current evidence in patients with SARS and MERS suggests that receiving corticosteroids did not have an effect on mortality, but rather delayed viral clearance.
,  
,  
 Therefore, corticosteroids should not be routinely given systemically, according to WHO interim guidance.
 Among our cohort of 41 laboratory-confirmed patients with 2019-nCoV infection, corticosteroids were given to very few non-ICU cases, and low-to-moderate dose of corticosteroids were given to less than half of severely ill patients with ARDS. Further evidence is urgently needed to assess whether systematic corticosteroid treatment is beneficial or harmful for patients infected with 2019-nCoV.
No antiviral treatment for coronavirus infection has been proven to be effective. In a historical control study,
 the combination of lopinavir and ritonavir among SARS-CoV patients was associated with substantial clinical benefit (fewer adverse clinical outcomes). Arabi and colleagues initiated a placebo-controlled trial of interferon beta-1b, lopinavir, and ritonavir among patients with MERS infection in Saudi Arabia.
 Preclinical evidence showed the potent efficacy of remdesivir (a broad-spectrum antiviral nucleotide prodrug) to treat MERS-CoV and SARS-CoV infections.
,  
 As 2019-nCoV is an emerging virus, an effective treatment has not been developed for disease resulting from this virus. Since the combination of lopinavir and ritonavir was already available in the designated hospital, a randomised controlled trial has been initiated quickly to assess the efficacy and safety of combined use of lopinavir and ritonavir in patients hospitalised with 2019-nCoV infection.
Our study has some limitations. First, for most of the 41 patients, the diagnosis was confirmed with lower respiratory tract specimens and no paired nasopharyngeal swabs were obtained to investigate the difference in the viral RNA detection rate between upper and lower respiratory tract specimens. Serological detection was not done to look for 2019-nCoV antibody rises in 18 patients with undetectable viral RNA. Second, with the limited number of cases, it is difficult to assess host risk factors for disease severity and mortality with multivariable-adjusted methods. This is a modest-sized case series of patients admitted to hospital; collection of standardised data for a larger cohort would help to further define the clinical presentation, natural history, and risk factors. Further studies in outpatient, primary care, or community settings are needed to get a full picture of the spectrum of clinical severity. At the same time, finding of statistical tests and p values should be interpreted with caution, and non-significant p values do not necessarily rule out difference between ICU and non-ICU patients. Third, since the causative pathogen has just been identified, kinetics of viral load and antibody titres were not available. Finally, the potential exposure bias in our study might account for why no paediatric or adolescent patients were reported in this cohort. More effort should be made to answer these questions in future studies.
Both SARS-CoV and MERS-CoV were believed to originate in bats, and these infections were transmitted directly to humans from market civets and dromedary camels, respectively.
 Extensive research on SARS-CoV and MERS-CoV has driven the discovery of many SARS-like and MERS-like coronaviruses in bats. In 2013, Ge and colleagues
 reported the whole genome sequence of a SARS-like coronavirus in bats with that ability to use human ACE2 as a receptor, thus having replication potentials in human cells.
 2019-nCoV still needs to be studied deeply in case it becomes a global health threat. Reliable quick pathogen tests and feasible differential diagnosis based on clinical description are crucial for clinicians in their first contact with suspected patients. Because of the pandemic potential of 2019-nCoV, careful surveillance is essential to monitor its future host adaption, viral evolution, infectivity, transmissibility, and pathogenicity.
This online publication has been corrected. The corrected version first appeared at thelancet.com on January 30, 2020
Contributors
BC and JW had the idea for and designed the study and had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. YWa, GF, XG, JiXu, HL, and BC contributed to writing of the report. BC contributed to critical revision of the report. YWa, GF, XG, JiXu, and HL contributed to the statistical analysis. All authors contributed to data acquisition, data analysis, or data interpretation, and reviewed and approved the final version.
Declaration of interests
All authors declare no competing interests.

Data sharing

The data that support the findings of this study are available from the corresponding author on reasonable request. Participant data without names and identifiers will be made available after approval from the corresponding author and National Health Commission. After publication of study findings, the data will be available for others to request. The research team will provide an email address for communication once the data are approved to be shared with others. The proposal with detailed description of study objectives and statistical analysis plan will be needed for evaluation of the reasonability to request for our data. The corresponding author and National Health Commission will make a decision based on these materials. Additional materials may also be required during the process.
Acknowledgments
This work is funded by the Special Project for Emergency of the Ministry of Science and Technology (2020YFC0841300) Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS 2018-I2M-1-003), a National Science Grant for Distinguished Young Scholars (81425001/H0104), the National Key Research and Development Program of China (2018YFC1200102), The Beijing Science and Technology Project (Z19110700660000), CAMS Innovation Fund for Medical Sciences (2016-I2M-1-014), and National Mega-projects for Infectious Diseases in China (2017ZX10103004 and 2018ZX10305409). We acknowledge all health-care workers involved in the diagnosis and treatment of patients in Wuhan; we thank the Chinese National Health Commission for coordinating data collection for patients with 2019-nCoV infection; we thank WHO and the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) for sharing data collection templates publicly on the website; and we thank Prof Chen Wang and Prof George F Gao for guidance in study design and interpretation of results.
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