Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

Abstract

Importance
In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.

Objective
To describe the epidemiological and clinical characteristics of NCIP.

Design, Setting, and Participants
Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.

Exposures
Documented NCIP.

Main Outcomes and Measures
Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.

Results
Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).

Conclusions and Relevance
In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

Full text

Clinical Characteristics of 138 Hospitalized Patients
With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China
Dawei Wang, MD; Bo Hu, MD; Chang Hu, MD; Fangfang Zhu, MD; Xing Liu, MD; Jing Zhang, MD; Binbin Wang, MD; Hui Xiang, MD;
Zhenshun Cheng, MD; Yong Xiong, MD; Yan Zhao, MD; Yirong Li, MD; Xinghuan Wang, MD; Zhiyong Peng, MD
IMPORTANCE In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP)
occurred in Wuhan, China. The number of cases has increased rapidly but information on the
clinical characteristics of affected patients is limited.
OBJECTIVE To describe the epidemiological and clinical characteristics of NCIP.
DESIGN, SETTING, AND PARTICIPANTS Retrospective, single-center case series of the 138
consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan
University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was
February 3, 2020.
EXPOSURES Documented NCIP.
MAIN OUTCOMES AND MEASURES Epidemiological, demographic, clinical, laboratory,
radiological, and treatment data were collected and analyzed. Outcomes of critically ill
patients and noncritically ill patients were compared. Presumed hospital-related transmission
was suspected if a cluster of health professionals or hospitalized patients in the same wards
became infected and a possible source of infection could be tracked.
RESULTS Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile
range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated
transmission was suspected as the presumed mechanism of infection for affected health
professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms
included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]).
Lymphopenia (lymphocyte count, 0.8 × 10
9
/L [interquartile range {IQR}, 0.6-1.1]) occurred in
97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80
patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients
(39.9%). Chest computed tomographic scans showed bilateral patchy shadows or
ground glass opacity in the lungs of all patients. Most patients received antiviral therapy
(oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89
[64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy
(62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU)
because of complications, including acute respiratory distress syndrome (22 [61.1%]),
arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to
dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days.
Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102),
were older (median age, 66 years vs 51 years), were more likely to have underlying
comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%]
vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%)
received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17
(47.2%) received invasive ventilation (4 were switched to extracorporeal membrane
oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall
mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged
alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).
CONCLUSIONS AND RELEVANCE In this single-center case series of 138 hospitalized patients
with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV
was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
JAMA. doi:10.1001/jama.2020.1585
Published online February 7, 2020.
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Author Affiliations: Author
affiliations are listed at the end of this
article.
Corresponding Author: Zhiyong
Peng, MD, Department of
Critical Care Medicine, Zhongnan
Hospital of Wuhan University,
Wuhan 430071, Hubei, China
(Pengzy5@hotmail.com).
Section Editor: Derek C. Angus, MD,
MPH, Associate Editor,JAMA
(angusdc@upmc.edu).
Research
JAMA | Original Investigation |CARING FOR THE CRITICALLY ILL PATIENT
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In December 2019, a cluster of acute respiratory illness, now
known as novel coronavirus–infected pneumonia (NCIP),
occurred in Wuhan, Hubei Province, China.
1-5
The disease
has rapidly spread from Wuhan to other areas. As of January
31, 2020, a total of 9692 NCIP cases in China have been
confirmed. Internationally, cases have been reported in 24
countries and 5 continents.
6
On January 3, 2020, the 2019 novel
coronavirus (2019-nCoV) was identified in samples of bron-
choalveolar lavage fluid from a patient in Wuhan and was con-
firmed as the cause of the NCIP.
7
Full-genome sequencing and
phylogenic analysis indicated that 2019-nCoV is a distinct clade
from the betacoronaviruses associated with human severe
acute respiratory syndrome (SARS) and Middle East respira-
tory syndrome (MERS).
7
The 2019-nCoV has features typical
of the coronavirus family and was classified in the betacoro-
navirus 2b lineage. The 2019-nCoV has close similarity to bat
coronaviruses, and it has been postulated that bats are the pri-
mary source. While the origin of the 2019-nCoV is still being
investigated, current evidence suggests spread to humans oc-
curred via transmission from wild animals illegally sold in the
Huanan Seafood Wholesale Market.
8
Huangetal
9
first reported 41 cases of NCIP in which most
patients had a history of exposure to Huanan Seafood Whole-
sale Market. Patients’ clinical manifestations included fever,
nonproductive cough, dyspnea, myalgia, fatigue, normal or de-
creased leukocyte counts, and radiographic evidence of pneu-
monia. Organ dysfunction (eg, shock, acute respiratory dis-
tress syndrome [ARDS], acute cardiac injury, and acute kidney
injury) and death can occur in severe cases.
9
Subsequently,
Chen et al
8
reported findings from 99 cases of NCIP from the
same hospital and the results suggested that the 2019-nCoV
infection clustered within groups of humans in close contact,
was more likely to affect older men with comorbidities, and
could result in ARDS. However, the difference in clinical char-
acteristics between severe and nonsevere cases was not re-
ported. Case reports confirmed human-to-human transmis-
sion of NCIP.
10,11
At present, there are no effective therapies
or vaccines for NCIP. The objective of this case series was to
describe the clinical characteristics of 138 hospitalized pa-
tients with NCIP and to compare severe cases who received in-
tensive care unit (ICU) care with nonsevere cases who did not
receive ICU care.
Methods
Study Design and Participants
This case series was approved by the institutional ethics board
of Zhongnan Hospital of Wuhan University (No. 2020020). All
consecutive patients with confirmed NCIP admitted to
Zhongnan Hospital of Wuhan University from January 1 to
January 28, 2020, were enrolled. Oral consent was obtained
from patients. Zhongnan Hospital, located in Wuhan, Hubei
Province, the endemic areas of NCIP, is one of the major ter-
tiary teaching hospitals and is responsible for the treatments
for NCIP assigned by the government. All patients with
NCIP enrolled in this study were diagnosed according to
World Health Organization interim guidance.
12
The clinical
outcomes (ie, discharges, mortality, length of stay) were moni-
tored up to February 3, 2020, the final date of follow-up.
Data Collection
The medical records of patients were analyzed by the re-
search team of the Department of Critical Care Medicine,
Zhongnan Hospital of WuhanUniversity.Epidemiologic al, clini-
cal, laboratory,and radiologic al characteristics and treatment
and outcomes data were obtained with data collection forms
from electronic medical records. The data were reviewed by a
trained team of physicians. Information recorded included
demographic data, medical history, exposure history, under-
lying comorbidities, symptoms, signs, laboratory findings, chest
computed tomographic (CT) scans, and treatment measures
(ie, antiviral therapy, corticosteroid therapy, respiratory sup-
port, kidney replacement therapy). The date of disease onset
was defined as the day when the symptom was noticed. Symp-
toms, signs, laboratory values, chest CT scan, and treatment
measures during the hospital stay were collected. ARDS was
defined according to the Berlin definition.
13
Acute kidney in-
jury was identified according to the Kidney Disease: Improv-
ing Global Outcomes definition.
14
Cardiac injury was defined
if the 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.
9
For patients admitted to the ICU, the
Glasgow Coma Scale, Sequential Organ Failure Assessment, and
Acute Physiology and Chronic Health Evaluation II scores were
determined on the day of ICU admission. The durations from
onset of disease to hospital admission, dyspnea, ARDS, and ICU
admission were recorded.
Presumed hospital-related transmission was suspected if
a cluster of medical professionals or hospitalized patients in
the same wards became infected in a certain time period and
a possible source of infection could be tracked.
Real-Time Reverse Transcription Polymerase Chain Reaction
Assay for nCoV
Throat swab samples were collected for extracting 2019-nCoV
RNA from patients suspected of having 2019-nCoV infection. Af-
ter collection, the throat swabs were placed into a collection tube
with 150 μL of virus preservation solution, and total RNA was
Key Points
Question What are the clinical characteristics of hospitalized
patients with 2019 novel coronavirus (2019-nCoV)–infected
pneumonia (NCIP) in Wuhan, China?
Findings In this single-center case series involving 138 patients
with NCIP, 26% of patients required admission to the intensive
care unit and 4.3% died. Presumed human-to-human
hospital-associated transmission of 2019-nCoV was suspected
in 41% of patients.
Meaning In this case series in Wuhan, China, NCIP was frequently
associatedwithpresumed hospital-related transmission,26%of patients
required intensive care unit treatment, and mortality was 4.3%.
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extracted within 2 hours using the respiratory sample RNA iso-
lation kit (Zhongzhi, Wuhan, China). In brief, 40 μL of cell ly-
sates were transferred into a collection tube followed by vortex
for 10 seconds. After standing at room temperature for 10 min-
utes, the collection tube was centrifugated at 1000 rpm/min for
5 minutes. The suspension was used for real-time reverse tran-
scription polymerase chain reaction (RT-PCR) assay of 2019-
nCoV RNA. Two target genes, including open reading frame 1ab
(ORF1ab) and nucleocapsid protein (N), were simultaneously am-
plified and tested during the real-time RT-PCR assay. Target 1
(ORF1ab): forward primer CCCTGTGGGTTTTACACTTAA;
reverse primer ACGATTGTGCATCAGCTGA; and the probe
5′-VIC-CCGTCTGCGGTATGTGGAAAGGTTATGG-BHQ1-3′.
Target 2 (N): forward primer GGGGAACTTCTCCTGCTAGAAT;
reverse primer CAGACATTTTGCTCTCAAGCTG; and the probe
5′-FAM- TTGCTGCTGCTTGACAGATT-TAMRA-3′. The real-
time RT-PCR assay was performed using a 2019-nCoV nucleic
acid detection kit according to the manufacturer’s protocol
(Shanghai bio-germ Medical Technology Co Ltd). Reaction mix-
ture contains 12 μL of reaction buffer, 4 μL of enzyme solution,
4 μL of Probe primers solution, 3 μL of diethyl pyrocarbonate–
treated water, and 2 μL of RNA template. RT-PCR assay was
Table 1. Baseline Characteristics of PatientsInfected With 2019-nCoV
No. (%)
PValue
a
Total (N = 138) ICU (n = 36) Non-ICU (n = 102)
Age, median (IQR), y 56 (42-68) 66 (57-78) 51 (37-62) <.001
Sex
Female 63 (45.7) 14 (38.9) 51 (37-62)
.34
Male 75 (54.3) 22 (61.1) 53 (52.0)
Huanan Seafood Wholesale Market exposure 12 (8.7) 5 (13.9) 7 (6.9) .30
Infected
Hospitalized patients 17 (12.3) 9 (25.0) 8 (7.8) .02
Medical staff 40 (29) 1 (2.8) 39 (38.2) <.001
Comorbidities 64 (46.4) 26 (72.2) 38 (37.3) <.001
Hypertension 43 (31.2) 21 (58.3) 22 (21.6) <.001
Cardiovascular disease 20 (14.5) 9 (25.0) 11 (10.8) .04
Diabetes 14 (10.1) 8 (22.2) 6 (5.9) .009
Malignancy 10 (7.2) 4 (11.1) 6 (5.9) .29
Cerebrovascular disease 7 (5.1) 6 (16.7) 1 (1.0) .001
COPD 4 (2.9) 3 (8.3) 1 (1.0) .054
Chronic kidney disease 4 (2.9) 2 (5.6) 2 (2.0) .28
Chronic liver disease 4 (2.9) 0 4 (3.9) .57
HIV infection 2 (1.4) 0 2 (2.0) >.99
Signs and symptoms
Fever 136 (98.6) 36 (100) 100 (98.0) >.99
Fatigue 96 (69.6) 29 (80.6) 67 (65.7) .10
Dry cough 82 (59.4) 21 (58.3) 61 (59.8) .88
Anorexia 55 (39.9) 24 (66.7) 31 (30.4) <.001
Myalgia 48 (34.8) 12 (33.3) 36 (35.3) .83
Dyspnea 43 (31.2) 23 (63.9) 20 (19.6) <.001
Expectoration 37 (26.8) 8 (22.2) 29 (28.4) .35
Pharyngalgia 24 (17.4) 12 (33.3) 12 (11.8) .003
Diarrhea 14 (10.1) 6 (16.7) 8 (7.8) .20
Nausea 14 (10.1) 4 (11.1) 10 (9.8) >.99
Dizziness 13 (9.4) 8 (22.2) 5 (4.9) .007
Headache 9 (6.5) 3 (8.3) 6 (5.9) .70
Vomiting 5 (3.6) 3 (8.3) 2 (2.0) .13
Abdominal pain 3 (2.2) 3 (8.3) 0 (0) .02
Onset of symptom to, median (IQR), d
Hospital admission 7.0 (4.0-8.0) 8.0 (4.5-10.0) 6.0 (3.0-7.0) .009
Dyspnea 5.0 (1.0-10.0) 6.5 (3.0-10.8) 2.5 (0.0-7.3) .02
ARDS 8.0 (6.0-12.0) 8.0 (6.0-12.0) 8.0 (6.3-11.3) .97
Heart rate, median (IQR), bpm 88 (78-97) 89 (81-101) 86 (77-96) .14
Respiratory rate, median (IQR) 20 (19-21) 20 (16-25) 20 (19-21) .57
Mean arterial pressure, median (IQR), mm Hg 90 (84-97) 91 (78-96) 90 (85-98) .33
Abbreviations: ARDS, acute
respiratory distress syndrome;
bpm, beats per minute; COPD,
chronic obstructive pulmonary
disease; ICU, intensive care unit;
IQR, interquartile range;
2019-nCoV,2019 novel coronavirus.
a
Pvalues indicate differences
between ICU and non-ICU patients.
P< .05 was considered statistically
significant.
Clinical Characteristics of Patients With 2019 Novel Coronavirus (2019-nCoV)–Infected Pneumonia in Wuhan, China Original Investigation Research
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performed under the following conditions: incubation at 50 °C
for 15 minutes and 95 °C for 5 minutes, 40 cycles of denatur-
ation at 94 °C for 15 seconds, and extending and collecting fluo-
rescence signal at 55 °C for 45 seconds. A cycle threshold value
(Ct-value) less than 37 was defined as a positive test result, and
a Ct-value of 40 or more was defined as a negative test. These
diagnostic criteria were based on the recommendation by the
National Institute for ViralDisease Control and Prevention (China)
(http://ivdc.chinacdc.cn/kyjz/202001/t20200121_211337.
html). A medium load, defined as a Ct-value of 37 to less than
40, required confirmation by retesting.
Statistical Analysis
Categorical variables were described as frequency rates and
percentages, and continuous variables were described using
mean, median, and interquartile range (IQR) values. Meansfor
continuous variables were compared using independent group
ttests when the data were normally distributed; otherwise, the
Mann-Whitney test was used. Data (nonnormal distribution)
from repeated measures were compared using the general-
ized linear mixed model. Proportions for categorical vari-
ables were compared using the χ
2
test, although the Fisher ex-
act test was used when the data were limited. All statistical
analyses were performed using SPSS (Statistical Package for
the Social Sciences) version 13.0 software (SPSS Inc). For un-
adjusted comparisons, a 2-sided α of less than .05 was con-
sidered statistically significant. The analyses have not been ad-
justed for multiple comparisons and, given the potential for
type I error, the findings should be interpreted as exploratory
and descriptive.
Results
Presenting Characteristics
The study population included 138 hospitalized patients with
confirmed NCIP. The median age was 56 years (IQR, 42-68;
range, 22-92 years), and 75 (54.3%) were men. Of these pa-
tients, 102 (73.9%) were admitted to isolation wards, and 36
(26.1%) were admitted and transferred to the ICU because of
the development of organ dysfunction (Table 1). The median
durations from first symptoms to dyspnea, hospital admis-
sion, and ARDS were 5 days (IQR, 1-10), 7 days (IQR, 4-8), and
8 days (IQR, 6-12), respectively (Table 1). Of the 138 patients,
64 (46.4%) had 1 or more coexisting medical conditions.
Hypertension (43 [31.2%]), diabetes (14 [10.1%]), cardiovascu-
lar disease (20 [14.5%]), and malignancy (10 [7.2%]) were the
most common coexisting conditions.
Table 2. Laboratory Findings of PatientsInfected With 2019-nCoV on Admission to Hospital
Normal Range
Median (IQR)
PValue
a
Total (N = 138) ICU (n = 36) Non-ICU (n = 102)
White blood
cell count, ×10
9
/L
3.5-9.5 4.5 (3.3-6.2) 6.6 (3.6-9.8) 4.3 (3.3-5.4) .003
Neutrophil
count, ×10
9
/L
1.8-6.3 3.0 (2.0-4.9) 4.6 (2.6-7.9) 2.7 (1.9-3.9) <.001
Lymphocyte
count, ×10
9
/L
1.1-3.2 0.8 (0.6-1.1) 0.8 (0.5-0.9) 0.9 (0.6-1.2) .03
Monocyte
count, ×10
9
/L
0.1-0.6 0.4 (0.3-0.5) 0.4 (0.3-0.5) 0.4 (0.3-0.5) .96
Platelet
count, ×10
9
/L
125-350 163 (123-191) 142 (119-202) 165 (125-188) .78
Prothrombin time, s 9.4-12.5 13.0 (12.3-13.7) 13.2 (12.3-14.5) 12.9 (12.3-13.4) .37
Activated partial
thromboplastin time, s
25.1-36.5 31.4 (29.4-33.5) 30.4 (28.0-33.5) 31.7 (29.6-33.5) .09
D-dimer, mg/L 0-500 203 (121-403) 414 (191-1324) 166 (101-285) <.001
Creatine kinase, U/L <171 92 (56-130) 102 (62-252) 87 (54-121) .08
Creatine
kinase–MB, U/L
<25 14 (10-18) 18 (12-35) 13 (10-14) <.001
Lactate
dehydrogenase, U/L
125-243 261 (182-403) 435 (302-596) 212 (171-291) <.001
Alanine
aminotransferase, U/L
9-50 24 (16-40) 35 (19-57) 23 (15-36) .007
Aspartate
aminotransferase, U/L
15-40 31 (24-51) 52 (30-70) 29 (21-38) <.001
Total bilirubin, mmol/L 5-21 9.8 (8.4-14.1) 11.5 (9.6-18.6) 9.3 (8.2-12.8) .02
Blood urea nitrogen,
mmol/L
2.8-7.6 4.4 (3.4-5.8) 5.9 (4.3-9.6) 4.0 (3.1-5.1) <.001
Creatinine, mol/L 64-104 72 (60-87) 80 (66-106) 71 (58-84) .04
Hypersensitive
troponin I, pg/mL
<26.2 6.4 (2.8-18.5) 11.0 (5.6-26.4) 5.1 (2.1-9.8) .004
Procalcitonin, ng/mL
≥0.05, No. (%) <0.05 49 (35.5) 27 (75.0) 22 (21.6) <.001
Bilateral distribution
of patchy shadows
or ground glass opacity,
No. (%)
NA 138 (100) 36 (100) 102 (100) >.99
Abbreviations: ICU, intensive care
unit; IQR, interquartile range;
MB, muscle and brain type; NA, not
available; 2019-nCoV, 2019 novel
coronavirus.
SI conversion factors: Toconvert
alanine aminotransferase to μkat/L,
multiply by 0.0167; aspartate
aminotransferase to μkat/L, multiply
by 0.0167; creatine kinase to μkat/L,
multiply by 0.0167; and lactate
dehydrogenase to μkat/L, multiply
by 0.016 7.
a
Pvalues indicate differences
between ICU and non-ICU patients.
P< .05 was considered statistically
significant.
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The most common symptoms at onset of illness were fe-
ver (136 [98.6%]), fatigue(96 [69.6%]), dry cough (82 [59.4%]),
myalgia (48 [34.8%]), and dyspnea (43 [31.2%]). Less com-
mon symptoms were headache, dizziness, abdominal pain,
diarrhea, nausea, and vomiting (Table 1). A total of 14 pa-
tients (10.1%) initiallypresented with diarrhea and nausea 1 to
2 days prior to development of fever and dyspnea.
Compared with patients who did not receive ICU care
(n = 102), patients who required ICU care (n = 36) were signifi-
cantly older (median age, 66 years [IQR, 57-78] vs 51 years
[IQR, 37-62]; P< .001) and were more likely to have underly-
ing comorbidities, including hypertension (21 [58.3%] vs 22
[21.6%], diabetes (8 [22.2%] vs 6 [5.9%]), cardiovascular dis-
ease (9 [25.0%] vs 11 [10.8%]), and cerebrovascular disease
(6 [16.7%] vs 1 [1.0%]). Compared with the non-ICU patients,
patients admitted to the ICU were morelikely to report pharyn-
geal pain, dyspnea, dizziness, abdominal pain, and anorexia.
Vital Signs and Laboratory Parameters
in ICU and Non-ICU Patients
Heart rate, respiratory rate, and mean arterial pressure did
not differ between patients who received ICU care and
patients who did not receive ICU care. These measures were
recorded on day of hospital admission for all patients, then
divided into those who were later admitted to the ICU or not.
There were numerous differences in laboratory findings
between patients admitted to the ICU and those not admit-
ted to the ICU (Table 2), including higher white blood cell
and neutrophil counts, as well as higher levels of D-dimer,
creatine kinase, and creatine. All of the 138 enrolled patients
showed bilateral involvement of chest CT scan (Figure 1).
The median time from onset of symptoms to ICU admission
was 10 days (IQR, 6-12) (Table 3). On the day of ICU admis-
sion, the median Glasgow Coma Scale; Acute Physiology and
Chronic Health Evaluation II; and Sequential Organ Failure
Assessment scores were 15 (IQR, 9-15), 17 (IQR, 10-22), and 5
(IQR, 3-6), respectively (Table 3). The median partial pressure
Table 3. Severity of Illness Scores and Blood Gas Analysis of Patients
Infected With 2019-nCoV in the ICU
Normal Range Median (IQR)
No. of patients 36
Onset of symptom to ICU admission, d NA 10 (6-12)
Time from hospital admission
to ICU admission, d
NA 1 (0-3)
Glasgow Coma Scale score NA 15 (9-15)
APACHE II NA 17 (10-22)
SOFA NA 5 (3-6)
PH 7.35-7.45 7.43 (7.39-7.47)
Lactate, mmol/L 0.5-1.6 1.3 (0.7-2.0)
PaO
2
, mm Hg 83-108 68 (56-89)
PaO
2
:FIO
2
, mm Hg 400-500 136 (103-234)
PaCO
2
, mm Hg 35-48 34 (30-38)
Abbreviations: APACHE II, Acute Physiology and Chronic Health Evaluation II;
FIO
2
, fraction of inspired oxygen; ICU, intensive care unit; IQR, interquartile
range; NA, not available; 2019-nCoV, 2019 novel coronavirus; PaCO
2
, partial
pressure of carbon dioxide; PaO
2
, partial pressure of oxygen; SOFA, Sequential
Organ Failure Assessment.
Figure 1. Chest Computed Tomographic Images of a 52-Year-OldPatient Infected With 2019 Novel Coronavirus (2019-nCoV)
A
Computed tomography images on day 5 after symptom onset
B
Computed tomography images after treatment on day 19 after symptom onset
A, Chest computed tomographic images obtained on January 7,2020, show
ground glass opacity in both lungs on day 5 after symptom onset. B, Images
taken on January 21, 2020,show the absorption of bilateral ground glass
opacity after the treatment of extracorporeal membrane oxygenation from
January 7 to 12 in the intensive care unit.
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of oxygen level was 68 mm Hg (IQR, 56-89) and the median
of partial pressure of oxygen to fraction of inspired oxygen
ratio was 136 mm Hg (IQR, 103-234).
Organ Dysfunctions and Main Interventions
The organ dysfunction and treatment of the 138 patients are
shown in Table 4. As of February 3, 2020, 85 patients (61.6%)
were still hospitalized. A total of 47 patients (34.1%) had been
discharged, and 6 patients (4.3%) had died. Of the 36 patients
admitted to the ICU, 11 were still in the ICU, 9 had been dis-
charged to home, 10 had been transferred to the general wards,
and 6 had died. Of the 11 patients who remained in the ICU,
6 received invasive ventilation (1 switched to extracorporeal
membrane oxygenation) and 5 to noninvasive ventilations).
Common complications among the 138 patients included shock
(12 [8.7%]), ARDS (27 [19.6%]), arrhythmia (23 [16.7%]), and
acute cardiac injury (10 [7.2%]). Patients who received care in
the ICU were more likely to have one of these complications
than non-ICU patients.
Most patients received antiviral therapy (oseltamivir,
124 [89.9%]), and many received antibacterial therapy
(moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithro-
mycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]).
In the ICU, 4 patients (11.1%) received high-flow oxygen
and 15 (44.4%) received noninvasive ventilation. Invasive
mechanical ventilation was required in 17 patients (47.2%), 4
of whom received extracorporeal membrane oxygenation as
rescue therapy. A total of 13 patients received vasopressors,
and 2 patients received kidney replacement therapy.
Dynamic Profile of Laboratory Findings in Patients
With NCIP
To determine the major clinical features that appeared
during NCIP progression, the dynamic changes in 6 clini-
cal laboratory parameters, including hematological and
biochemical parameters, were tracked from day 1 to day 19
after the onset of the disease at 2-day intervals. At the end of
January 28, 2020, data from 33 patients with complete clini-
cal course were analyzed (Figure 2). During hospitalization,
most patients had marked lymphopenia, and nonsurvi-
vors developed more severe lymphopenia over time. White
blood cell counts and neutrophil counts were higher in non-
survivors than those in survivors. The level of D-dimer was
higher in nonsurvivors than in survivors. Similarly, as the
disease progressed and clinical status deteriorated, the lev-
els of blood urea and creatinine progressively increased
before death.
Presumed Hospital-Related Transmission and Infection
Of the 138 patients, 57 (41.3%) were presumed to have been
infected in hospital, including 17 patients (12.3%) who were
already hospitalized for other reasons and 40 health care work-
ers (29%). Of the hospitalized patients, 7 patients were from
the surgical department, 5 were from internal medicine, and
5 were from the oncology department. Of the infected health
care workers, 31 (77.5%) worked on general wards, 7 (17.5%)
in the emergency department, and 2 (5%) in the ICU. One pa-
tient in the current study presented with abdominal symp-
toms and was admitted to the surgical department. More than
10 health care workers in this department were presumed to
have been infected by this patient. Patient-to-patient trans-
mission also was presumed to have occurred, and at least
4 hospitalized patients in the same ward were infected, and
all presented with atypical abdominal symptoms. One of the
4 patients had fever and was diagnosed as having nCoV infec-
tion during hospitalization. Then, the patient was isolated.
Subsequently, the other 3 patients in the same ward had
fever, presented with abdominal symptoms, and were diag-
nosed as having nCoV infection.
Discussion
This report, to our knowledge, is the largest case series to
date of hospitalized patients with NCIP. As of February 3,
2020, of the 138 patients included in this study, 26% required
Table 4.Complications and Treatments of Patients Infected With 2019-nCoV
No. (%)
PValue
a
Total (N = 138) ICU (n = 36) Non-ICU (n = 102)
Complications
Shock 12 (8.7) 11 (30.6) 1 (1.0) <.001
Acute cardiac injury 10 (7.2) 8 (22.2) 2 (2.0) <.001
Arrhythmia 23 (16.7) 16 (44.4) 7 (6.9) <.001
ARDS 27 (19.6) 22 (61.1) 5 (4.9) <.001
AKI 5 (3.6) 3 (8.3) 2 (2.0) .11
Treatment
Antiviral therapy 124 (89.9) 34 (94.4) 90 (88.2) .36
Glucocorticoid therapy 62 (44.9) 26 (72.2) 36 (35.3) <.001
CKRT 2 (1.45) 2 (5.56) 0 >.99
Oxygen inhalation 106 (76.81) 4 (11.11) 102 (100) <.001
NIV 15 (10.9) 15 (41.7) 0 <.001
IMV 17 (12.32) 17 (47.22) 0 <.001
ECMO 4 (2.9) 4 (11.1) 0 .004
Abbreviations: AKI, acute kidney
injury; ARDS, acute respiratory
distress syndrome; CKRT, continuous
kidney replacement therapy;
ECMO, extracorporeal membrane
oxygenation; ICU, intensive care unit;
IMV,invasive mechanical ventilation;
NIV,noninvasive ventilation;
2019-nCoV,2019 novel coronavirus.
a
Pvalues indicate differences
between ICU and non-ICU patients.
P< .05 was considered statistically
significant.
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ICU care, 34.1% were discharged, 6 died (4.3%), and 61.6%
remain hospitalized. For those who were discharged (n = 47),
the hospital stay was 10 days (IQR, 7.0-14.0). The time from
onset to dyspnea was 5.0 days, 7.0 days to hospital admis-
sion, and 8.0 days to ARDS. Common symptoms at onset of
illness were fever, dry cough, myalgia, fatigue, dyspnea, and
anorexia. However, a significant proportion of patients
presented initially with atypical symptoms, such as diarrhea
and nausea. Major complications during hospitalization
included ARDS, arrhythmia, and shock. Bilateral distribution
of patchy shadows and ground glass opacity was a typical
hallmark of CT scan for NCIP. Most critical ill patients were
older and had more underlying conditions than patients not
admitted to the ICU. Most patients required oxygen therapy
Figure 2. Dynamic Profile of Laboratory Parameters in 33 Patients With Novel Coronavirus–InfectedPneumonia (NCIP)
250
200
150
100
50
0
35
20
25
30
15
10
5
0
1500
1000
500
0
–500
1.6
0.8
1.0
1.2
1.4
0.6
0.4
0.2
0
16
8
10
12
14
6
4
2
0
18
8
10
12
14
16
6
4
2
0
White Blood Cell Count, ×109
Days After Disease Onset
White blood cells
A
0 3 5 7 9
a
11
a
13 17
a
15
a
19
Neutrophil Count, ×109/L
Days After Disease Onset
Neutrophil count
B
0 3 5 7 9
a
11
a
13 1715
a
19
Lymphocyte Count, ×109/L
Days After Disease Onset
Lymphocyte count
C
0 3 5 7
a
9 11 13
a
17
a
15 19
D-dimer, mg/L
Days After Disease Onset
D-dimer
D
0 3 5 7 9 11 13
a
Blood Urea Nitrogen, mmol/L
Days After Disease Onset
Blood urea nitrogen
E
0 3 5 7 9 11 13
a
15
a
17
a
Creatinine, µmol/L
Days After Disease Onset
Creatinine
F
0 3 5 7 9 11 13 15 17
a
P <.05 P <.05
P <.05
P <.05
P <.05 P <.05
Nonsurvivors
Nonsurvivors
Nonsurvivors
Nonsurvivors
Nonsurvivors
Nonsurvivors
Survivors
Survivors
Survivors
Survivors
Survivors
Survivors
Timeline charts illustrate the laboratory parameters in 33 patients with NCIP (5 nonsurvivors and 28 survivors) every other day based on the days after the onset
of illness. The solid lines in black show the upper normal limit of each parameter, and the solid line in red shows the lowernormal limit of lymphoc yte count.
a
P< .05 for nonsurvivors vs survivors.
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and a minority of the patients needed invasive ventilation or
even extracorporeal membrane oxygenation.
The data in this study suggest rapid person-to-person
transmission of 2019-nCoV may have occurred. The main rea-
son is derived from the estimation of the basic reproductive
number (R
0
) based on a previous study.
15
R
0
indicates how con-
tagious an infectious disease is. As an infection spreads to new
people, it reproduces itself; R
0
indicates the average number
of additional individuals that one affected case infects during
the course of their illness and specifically applies to a popu-
lation of people who were previously free of infection and have
not been vaccinated. Based on the report, R
0
from nCoV is 2.2,
which estimated that, on average, each patienthas been spread-
ing infection to 2.2 other people.
15
One reason for the rapid
spread may be related to the atypical symptoms in the early
stage in some patients infected with nCoV.
A recent study showed that nCoV was detected in stool
samples of patients with abdominal symptoms.
16
However,
it is difficult to differentiate and screen patients with atypical
symptoms. Nevertheless, the rapid human-to-human trans-
mission among close contacts is an important feature in
nCoV pneumonia.
10,11,15
The patients admitted to the ICU were older and had a
greater number of comorbid conditions than those not ad-
mitted to the ICU. This suggests that age and comorbidity
may be risk factors for poor outcome. However, there was
no difference in the proportion of men and women between
ICU patients and non-ICU patients. These data differ from
the recent report that showed 2019-nCoV infection is more
likely to affect males.
8
The possible explanation is that the
nCoV infection in patients in the previous report was related
to exposure associated with the Huanan Seafood Wholesale
Market, and most of the affected patients were male work-
ers. Compared with symptoms in non-ICU patients, symp-
toms were more common in critically ill patients, including
dyspnea, abdominal pain, and anorexia. The onset of symp-
toms may help physicians identify the patients with poor
prognosis. In this cohort, the overall rates of severe hypoxia
and invasive ventilation were higher than those in the pre-
vious study,
9
likely because the cases in the previous study
were from the early epidemic stage of the NCIP, and the cur-
rent cases are from the stage of outbreak.
The most common laboratory abnormalities observed in
this study were depressed total lymphocytes, prolonged pro-
thrombin time, and elevated lactate dehydrogenase. Com-
pared with non-ICU patients, patients who received ICU care
had numerous laboratory abnormalities. These abnormali-
ties suggest that 2019-nCoV infection may be associated with
cellular immune deficiency, coagulation activation, myocar-
dia injury, hepatic injury, and kidney injury. These laboratory
abnormalities are similar to those previously observed in pa-
tients with MERS-CoV and SARS-CoV infection.
The dynamic profile of laboratory findings was tracked in
33 patients with NCIP (5 nonsurvivors and 28 survivors). In the
nonsurvivors, the neutrophil count, D-dimer, blood urea, and
creatinine levels continued to increase, and the lymphocyte
counts continued to decrease until death occurred. Neutro-
philia may be related to cytokine storm induced by virus in-
vasion, coagulation activation could have been related tosus-
tained inflammatory response, and acute kidney injury could
have been related to direct effects of the virus, hypoxia, and
shock. The 3 pathologic mechanisms may be associated with
the death of patients with NCIP.
Until now, no specific treatment has been recommended
for coronavirus infection except for meticulous supportive
care.
17
Currently, the approach to this disease is to control
the source of infection; use of personal protection precaution
to reduce the risk of transmission; and early diagnosis,
isolation, and supportive treatments for affected patients.
Antibacterial agents are ineffective. In addition, no anti-
viral agents have been found to provide benefit for treating
SARS and MERS. All of the patients in this study received
antibacterial agents, 90% received antiviral therapy, and 45%
received methylprednisolone. The dose of oseltamivir and
methylprednisolone varied depending on disease severity.
However, no effective outcomes were observed.
This study has several limitations. First, respiratory tract
specimens were used to diagnose NCIP through RT-PCR.
The serum of patients was not obtained to evaluate the
viremia. The viral load is a potentially useful marker associ-
ated with disease severity of coronavirus infection, and this
should be determined in NCIP. Second, hospital-related
transmission/infection could not be definitively proven but
was suspected and presumed based on timing and patterns
of exposure to infected patients and subsequent develop-
ment of infection. Third, among the 138 cases, most patients
are still hospitalized at the time of manuscript submission.
Therefore, it is difficult to assess risk factors for poor out-
come, and continued observations of the natural history of
the disease are needed.
Conclusions
In this single-center case series of 138 hospitalized patients with
confirmed NCIP in Wuhan, China, presumed hospital-related
transmission of 2019-nCoV was suspected in 41% of patients,
26% of patients received ICU care, and mortality was 4.3%.
ARTICLE INFORMATION
Accepted for Publication: February 3, 2020.
Published Online: February 7, 2020.
doi:10.1001/jama.2020.1585
Author Affiliations: Department of Critical Care
Medicine, Zhongnan Hospital of Wuhan University,
Wuhan, Hubei, China (D. Wang, B. Hu, C. Hu, Zhu,
Liu, Zhang, B. Wang, Xiang, Peng); Department of
Pulmonary Medicine, Zhongnan Hospital of Wuhan
University,Wuhan, Hubei, China (Cheng );
Department of Infectious Disease, Zhongnan
Hospital of Wuhan University,Wuhan, Hubei, China
(Xiong); Department of Emergency Medicine,
Zhongnan Hospital of Wuhan University, Wuhan,
Hubei, China (Zhao); Department of Laboratory
Medicine, Zhongnan Hospital of Wuhan University,
Wuhan, Hubei, China (Li); Department of Urology,
Zhongnan Hospital of Wuhan University, Wuhan,
Hubei, China (X. Wang).
Author Contributions: Drs D. Wang and Penghad
full access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis. Drs D. Wang
and B. Hu contributed equally and share first
authorship. Drs Peng and X. Wang contributed
equally to this article.
Research Original Investigation Clinical Characteristics of Patients With 2019 Novel Coronavirus (2019-nCoV)–Infected Pneumonia in Wuhan, China
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Concept and design: D. Wang, B. Hu, C. Hu, Xiong,
Zhao, Li, X. Wang, Peng.
Acquisition, analysis, or interpretation of data:
D. Wang, C. Hu, Zhu, Liu, Zhang, B. Wang,Xiang,
Cheng, Xiong, Peng.
Drafting of the manuscript: D. Wang,C. Hu, Xiang,
Xiong, Li, Peng.
Critical revision of the manuscript for important
intellectual content: D. Wang, B. Hu, Zhu, Liu,
Zhang, B. Wang, Cheng, Xiong, Zhao, X. Wang,
Peng.
Statistical analysis: C. Hu, Zhu, Liu, B. Wang, Xiong.
Obtained funding: D. Wang, Peng.
Administrative, technical, or material support: B. Hu,
Xiang, Cheng, Xiong, Li, X. Wang.
Supervision: B. Hu, Xiong, Zhao, X. Wang, Peng.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported
by the National Natural Science Foundation
(grant 81701941 to Dr D. Wang;grants 81772046
and 81971816 to Dr Peng) and the Special Project
for Significant New Drug Research and
Development in the Major National Science and
Technology Projects of China (2020ZX09201007
to Dr Peng).
Role of the Funder/Sponsor:The funders had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
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