The Lancet Infectious Diseases

Deep Learning-Based Quantitative Computed Tomography model in Predicting the

Severity of COVID-19: A Retrospective Study in 196 Patients

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--Manuscript Draft--

Manuscript Number: THELANCETID-D-20-00601

Article Type: Article (Original Research)

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Keywords: Corona Virus Disease 2019, Computed tomography, Deep learning, Multivariate
analysis, Predicting

Corresponding Author: Weiya Shi

CHINA

First Author: Weiya Shi

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Order of Authors: Weiya Shi

Xueqing Peng

Tiefu Liu

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Zenghui Cheng

Hongzhou Lu

Shuyi Yang

Jiulong Zhang

Feng Li
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Mei Wang

Xinlei Zhang

Yaozong Gao

Yuxin Shi
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Zhiyong Zhang

Fei Shan

Manuscript Region of Origin: CHINA

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Abstract: Background

The assessment of the severity of Corona Virus Disease 2019 (COVID-19) by clinical
presentations cannot met the urgently clinical need so far. We aimed to establish a
model of deep learning (DL)-based quantitative computed tomography (CT) and initial
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clinical features in prediction of the severity of COVID-19.

Methods

One hundred and ninety-six hospitalized patients with COVID-19 were enrolled from
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Jan 20 to Feb 10, 2020 in our center, and were divided into the severe and non-severe
group. The clinico-radiological data at admission were compared between the two
groups. A least absolute shrinkage and selection operator (LASSO) logistic regression
model for predicting the severity of COVID-19 was established, and the area under the
receiver operating characteristic (AUC) values of the model, quantitative CT
parameters significantly different in univariate analysis, and pneumonia severity index
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(PSI) were compared.

Findings

In comparison with non-severe group (151 cases), severe patients (45 cases) had
higher PSI (p<0.001). DL-based quantitative CT indicated that the mass of infection

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 (MOI CT ) and the percentage of infection (POI CT ) in the severe group was higher
(p<0.001).The LASSO logistic regression model was based on MOI CT together with
clinical features including age, lactate dehydrogenase (LDH), C-reactive protein (CRP),
CD4 + T cell counts. The AUC value for the model was 0.890, and was significantly

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higher than that for MOI CT , POI CT , or PSI score (all p<0.01).

Interpretation

The DL-based quantitative CT model has more efficiency in predicting the severity of
COVID-19 than quantitative CT parameters and PSI score do.

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Manuscript

Deep Learning-Based Quantitative Computed Tomography model in Predicting

the Severity of COVID-19: A Retrospective Study in 196 Patients

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Weiya Shi1*, Xueqing Peng2*, Tiefu Liu3*, Zenghui Cheng4, Hongzhou Lu1, Shuyi Yang1, Jiulong
Zhang1, Feng Li5, Mei Wang5, Xinlei Zhang1, Yaozong Gao6, Yuxin Shi1, Zhiyong Zhang1†, Fei
Shan1†

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1
Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,
China;

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2
Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;
3
Department of Scientific Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai
201508, China;
4
Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,

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Shanghai 200025, China;
5
Department of Respiration, Shanghai Public Health Clinical Center, Fudan University, Shanghai
201508, China;
6
Department of Research and Development, Shanghai United Imaging Intelligence Inc., Shanghai
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200237, China.

*Contributed equally
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Correspondence to: Fei Shan; Zhiyong Zhang. Department of Radiology, Shanghai Public Health
Clinical Center, Fudan University, Shanghai 201508, China. Email: shanfei@shphc.org.cn (F Shan);
zhangzy@fudan.edu.cn (Z Zhang).
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Abstract
Background: The assessment of the severity of Corona Virus Disease 2019 (COVID-19) by clinical

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presentations cannot met the urgently clinical need so far. We aimed to establish a model of deep learning
(DL)-based quantitative computed tomography (CT) and initial clinical features in prediction of the
severity of COVID-19.
Methods: One hundred and ninety-six hospitalized patients with COVID-19 were enrolled from Jan 20

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to Feb 10, 2020 in our center, and were divided into the severe and non-severe group. The clinico-
radiological data at admission were compared between the two groups. A least absolute shrinkage and
selection operator (LASSO) logistic regression model for predicting the severity of COVID-19 was
established, and the area under the receiver operating characteristic (AUC) values of the model,
quantitative CT parameters significantly different in univariate analysis, and pneumonia severity index

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(PSI) were compared.
Findings: In comparison with non-severe group (151 cases), severe patients (45 cases) had higher PSI
(p<0.001). DL-based quantitative CT indicated that the mass of infection (MOICT) and the percentage of
infection (POICT) in the severe group was higher (p<0.001).The LASSO logistic regression model was

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based on MOICT together with clinical features including age, lactate dehydrogenase (LDH), C-reactive
protein (CRP), CD4+ T cell counts. The AUC value for the model was 0.890, and was significantly higher
than that for MOICT, POICT, or PSI score (all p<0.01).
Interpretation: The DL-based quantitative CT model has more efficiency in predicting the severity of
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COVID-19 than quantitative CT parameters and PSI score do.
Key words: Corona Virus Disease 2019, Computed tomography, Deep learning, Multivariate analysis,
Predicting
Funding: None.
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Introduction
Since December 2019, the outbreak of Corona Virus Disease 2019 (COVID-19) by SARS-CoV-2

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coronavirus infection in China has rapidly spread to many countries around the globe.1 Up to February
24, 79331 cases have been confirmed in world, and 2618 of them have died according to the WHO
statistics.2 With a death toll exceeding that of the SARS-CoV outbreak in 2002 and 2003, COVID-19
has led to a public health emergency of international concern, putting all health organizations on high

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alert.3
The current knowledge deems COVID-19 an acute self-limited disease, however, it can also be lethal
with a case fatality rate of 2%,4 making it the third lethal disease caused by the coronavirus family in
comparison with the fatality rates of 10% in SARS-CoV infection and 37% in MERS-CoV infection.5
Although the fatality rate of COVID-19 is relatively lower, it is such a respiratory disease that can spread

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widely and quickly and transmit from person-to-person.6 In addition, it was reported that 17% to 29% of
patients with COVID-19 could develop into severe or even lethal respiratory diseases such as acute
respiratory distress syndrome (ARDS).7-9 COVID-19 pandemic attracts the world’s attention but there is
still no efficient treatments and control strategies available today. Therefore, in addition to early diagnosis

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and isolation, timely identification of those patients who may develop into critically ill is pivotal for the
subsequently active intervention so as to improve clinic outcomes.
To date, despite several preliminary studies have reported clinical and imaging features of COVID-
19,7-10 the comprehensive prediction of disease severity is limited. Previous studies have demonstrated
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that the extent of air space consolidations or ground-glass opacity (GGO) on chest CT, which was
significantly different between the ARDS and non-ARDS group, may play an important prognostic role
in viral pneumonias such as H1N1, severe acute respiratory syndrome (SARS), and Middle East
respiratory syndrome (MERS).11-13 In recent years, Deep Learning (DL), which is one of the major
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subfields in Artificial Intelligence (AI), has played a central role in image analysis and has been proposed
as a potential method to analyze diffuse lung disease on CT.14,15 Automatic measurement of lesion extent
using DL will certainly show better performance as compared to the traditional visual evaluation on CT.
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Therefore, we hypothesize that DL-based quantitative CT measurement of lesion extent at admission,

together with clinical features, will help in predicting the severity of COVID-19 so as to triage patients,
design treatment protocol and follow-up evaluation in advance. In this retrospective study, we will
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characterize these baseline clinico-radiological features and establish a model to predict prognosis of
COVID-19.

Methods
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Study design and participants

The Institutional Review Board of Shanghai Public Health Clinical Center, Fudan University approved
the study protocol. Informed consent was waived because of the retrospective nature of the study. A total
of 196 patients with confirmed COVID-19 were enrolled from January 20 to February 10, 2020, in our
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center. The patients’ inclusion criteria were: a) patients with a positive new coronavirus nucleic acid
through real-time PCR (RT-PCR) detected by the Center for Disease Control (CDC), Shanghai, and re-
checked by national CDC; b) patients with chest thin-section CT scanning; c) CT images demonstrated
pneumonia. Ten patients with normal chest CT imaging were excluded. One patient with COVID-19 was
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co-infected with influenza B virus.

According to COVID-19 Guidelines (the fifth version) made by National Health Commission of the
People’s Republic of China,16 patients with COVID-19 could divided into four subtypes: mild, common,

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 severe and critically ill subtypes. As the mild subtype with no pneumonia was excluded, we divided the
patients enrolled in this study into two groups: no-severe group (common subtype) and severe group

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(severe and critically ill subtypes). The non-severe group was consisted of 151 patients. The severe group
was consisted of 45 patients, of them 17 patients were critically ill subtype, 28 patients were severe
subtype.
Clinical data collection

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The medical records of these patients were reviewed. Particular attention was paid to the
epidemiological, medical and exposure histories, co-comorbidities, symptoms, signs, laboratory findings,
treatment and outcomes data. The date of disease onset was defined as the day when the symptom was
noticed. All enrolled patients underwent pneumonia severity index (PSI) score.17 The data were reviewed
and the PSI was evaluated by two respirologists (Mei Wang and Feng Li, with 13 and 19 years of

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experience in respiration medicine, respectively).
CT imaging acquiring
All patients underwent the thoracic CT examinations with a 64-section scanner (Scenaria, HITACHI,
Japan) at full inspiration. Scanning range was from the level of the thoracic inlet to the inferior level of

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the costophrenic angle. The scanning protocols were as follows: detector width, 64 × 0.625 mm; pitch,
1.57; tube voltage, 120Kv; automatic tube current with Advanced Mode (maximum: 400mA, minimum:
150mA); rotation time, 0.35 seconds; matrix, 512 × 512. Reconstruction was kernel used was lung
smooth with a thickness of 1 mm and an interval of 0.8 mm. The following windows were used: a
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mediastinal window with a window width of 350 HU and a window level of 40 HU, and a lung window
with a width of 1200 HU and a level of -600 HU.
Image interpretation
All CT images were evaluated for lesions distribution, pulmonary opacities category, lesion-related
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signs (air bronchogram), focal pulmonary fibrosis (including reticulation and liner opacity), pleural
effusion, mediastinal lymphadenopathy (>1 cm in short-axis diameter). The number of
pulmonary segments involved were also counted. If the number of pulmonary segments involved in
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inferior lobes was more than half of the total pulmonary segments involved, it would been defined as
inferior lobes preference. The location of the lesion was classified as the predominantly central or
predominantly peripheral according to the location at either the inner or outer half of the lung field.
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According to the CT features of COVID-19 in our study, we categorized the pulmonary opacities into
4 types (Figure 1): type I, pure ground-glass opacities (pGGOs), which manifested as a hazy opacity
without obscuring the underlying pulmonary parenchyma; type II, GGOs with consolidation, which was
defined as pGGOs with the area of consolidation obscuring the underlying pulmonary parenchyma; type
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III, GGOs with interlobular septal thickening or reticulation as crazy-paving sign; type IV, the
consolidation, which was defined as the lesions obscuring the underlying pulmonary parenchyma.
All the terms were defined according to the Fleischner Society.18 The CT images were analyzed
independently by two radiologists (Weiya Shi and Fei Shan, with 12 and 19 years of experience in chest
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radiology, respectively), who evaluated images without any previous knowledge of the patients’ clinical
or laboratory findings. In cases of disagreement, the final results were determined by consensus between
the two radiologists.
Quantitative CT analysis
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The volume and mass of infected regions as shown on CT (slice thickness = 1mm) in patients with
COVID-19 were quantified by uAI-Discover-NCP (beta version) developed by Shanghai United Imaging
Intelligence Inc, China. The software utilized the V-Net network architecture (Figure 2), which was one

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 of convolutional neural networks (CNNs),19 and combined it with transfer learning to segment both lung
fields and lung infected regions on chest CT images. The procedure was carried in two steps. In the

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training step, the lung fields and lung infected regions were manually annotated by senior radiologists.
These data served as training data to learn a neural network model. In the application step, the learned
model was used to automatically extract lung and lung infected regions from new chest CT images, and
the volume of infected regions could be calculated. The affected regions were mainly composed of GGO

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and consolidation. A range between -750 HU and -300HU was defined as the region of GGO, and a range
between -300 HU and 50HU was defined as the region of consolidation, as previous report.20
The percentage of infection (POICT) in whole lung was calculated as the infection volume divided by
the whole lung volume. The percentage of consolidation (POCCT) in infected regions was calculated as
the volume of consolidation divided by the whole infection volume. In addition, the mass of infection

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(MOICT) in whole lung was also included in the quantitative analysis. Mass was calculated according to
the following equation, as previously adopted:21 M = V * [(Amean+1000) * 0.001], where M was the mass
in milligrams per millimeter, V was the infection volume, Amean was the mean attenuation in Hounsfield
units.

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Statistical analysis
Statistical analysis was performed by R version 3.6.1 (R Project for Statistical Computing, Vienna,
Austria). Because a majority of the continuous data did not follow a normal distribution, all of the data
were expressed as the median and interquartile range (IQR, 25th and 75th percentiles). Wilcoxon rank-
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sum test was used for quantitative variables, and the Fisher’s exact test and the chi-square test were used
for categoric variables when comparing the severe group with the non-severe group.
A least absolute shrinkage and selection operator (LASSO) logistic regression was used to select the
optimal subset of clinico-radiological features in order to develop the signature score for predicting
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prognosis. Increasing the tuning parameter (λ) made more coefficients set to zero (less variables are

selected), and among the non-zero coefficients, more shrinkage was employed. The area under the
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receiver operating characteristic curve (AUC) was plotted versus log(λ) in order to identify the optimal
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value of log(λ). The optimal value was identified by the minimum criterion and the one standard error of

the minimum criterion.

Receiver operating characteristic (ROC) analyses were conducted for the LASSO logistic regression
model as well as for the continuous variables that were found to show statistically significant differences
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in univariate analysis. The AUC values were used to evaluate the effect of the classifier when comparing
the severe group with the non-severe group. The cutoff values were defined as those for which the
Youden index was maximal. Delong test was employed to figure out the differences between the AUCs
above. A two-tailed α less than 0.05 was considered as statistically significant.
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Results
Clinical and laboratory features
Of the 196 enrolled patients, the median age was 52 years (IQR, 38-65; range, 16-88 years), and 105
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(53.6%) were men (Table 1). The median age of severe group (45 cases) was older than that of the non-
severe group (151 cases) (65 years vs. 46 years, p<0.001). More non-severe patients had the history of
epidemic source area exposure in comparison with the severe group (67.5% vs. 42.2%, p=0.003). Severe

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 group was more frequently with comorbidities as compared with the non-severe group (55.6% vs. 31.1%,
p=0.004), particularly the cardiovascular disease (15.6% vs. 4.0%, p=0.01).

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There were numerous differences in laboratory findings between the two groups (Table 2), including
higher neutrophil counts and higher serum levels of D-dimer, aspartate aminotransferase, lactate
dehydrogenase (LDH), serum troponin I, serum myoglobin, procalcitonin and c-reactive protein (CRP),
as well as lower levels of lymphocyte counts, CD4+ T cell counts and albumin (all p<0.001).

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The severe group had higher PSI than the non-severe group (66 [IQR, 54-82] vs. 48 [IQR, 35-61.5],
p<0.001).
CT morphological features and quantitative CT characteristics
The CT morphological features and quantitative CT characteristics of the 196 patients were shown in
Table 3. The most common types of pulmonary opacities were type III (71.4%) and Type II (70.9%). The

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lesions distributed more peripherally (88.3%), usually with inferior lobes predominance (61.7%). Neither
frequency of each type of the lesions nor distribution preference in inferior lobes and in the peripheral
part of lung were significantly different between the two groups. The number of pulmonary segments
involved in the severe group was more than that in the non-severe group (15 [IQR, 12-18] vs. 7 [IQR, 3-

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13.5], p<0.001). Bilateral lung involvement, air bronchogram and pleural effusion were more frequent
in the severe group than that in the non-severe group (95.6% vs. 80.1%, p=0.01; 86.7% vs. 69.5%, p=0.02;
11.1% vs. 2.6%, p=0.03).
In term of quantitative CT parameters, the POICT and the MOICT in the severe group were higher than
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that in the non-severe group (11.1% [IQR, 5.3%-22.7%] vs. 2.3% [IQR, 0.8%-4.8%], p<0.001;
257052.0mg [IQR, 113596.0-456735.0] vs. 52535.4mg [IQR, 19200.5-106885.5], p<0.001) (Figure 3
and 4). There was no significantly difference in the POCCT between the two groups.
Comparison of capacity for predicting severity of COVID-19
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λ in the LASSO model was selected using 10-fold cross-validation and log(λ) of –2.582 was chosen

for the optimal subset of the clinico-radiological features. At this value, 24 clinico-radiological features
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were reduced to 5 potential predictors with non-zero coefficients in the LASSO logistic regression model

(Figure 5). Figure 5 respectively shows that, as the log(λ) changes from – 10 to 0, the number of variables
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that entered into the model is reduced, and the absolute values of the coefficients of the variables also
shrink toward zero.
Based on the five clinico-radiological features including age, LDH, CRP, CD4+ T cell counts and
MOICT, the signature score was calculated for each patient. The signature score could be calculated
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according to the following equation: y=-3.790 + 1.498e-02 * age (years) + 4.717e-03 * LDH (U/L) +

4.661e-03 * CRP (mg/L) - 8.450e-05 * CD4+ T cell counts (cell/μL) + 2.073e-06 * MOI (mg). The cutoff

value on the ROC curve was -1.238 for predictive probability using the signature score. When the
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signature score value exceeded -1.238, it was predicted to be severe case.

The ability of LASSO logistic regression model, MOICT, POICT and PSI score to predict the severity
of COVID-19 were compared by Delong test (Table 4). The AUC value for the LASSO logistic model
was 0.890 (sensitivity, 82.2%; specificity, 82.8%; accuracy, 82.7%), and the AUC values for the other
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three parameters were 0.813, 0.805, and 0.751, respectively. The cutoff value on the ROC curve was
107720.0mg for predictive probability using MOICT, 5.9% for POICT, and 63.5 points for PSI. The
LASSO logistic regression model had significantly better prediction performance than MOICT, POICT or

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 PSI score (p=0.002, p<0.001, and p<0.001, respectively) (Figure 6).

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Discussion
The outbreak of the COVID-19 began in December 2019 in Wuhan, Hubei province, and rapidly
spread to many provinces in China as well as other countries. Here we reported the epidemiological,
clinical, laboratory, and radiological characteristics of a cohort of 196 patients with confirmed COVID-

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19 admitted to our hospital in Shanghai, China. We evaluated the baseline factors that influence prognosis
of COVID-19 and determined whether DL-based quantitative CT model could predict the severity of this
disease.
In our cohort, older male patients with comorbidities, especially cardiovascular disease, were more
likely to develop to the severe condition. In accordance with the previous reports,7-9 our data indicated

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that aging and co-existing comorbidities are risk factors for predicting the severity of COVID-19. Besides
the clinical symptoms, some laboratory findings also help in predicting disease severity. For example, in
severe group, the decreases in lymphocytes especially CD4+ T cells suggest the inhibition of immune
function by the consumption of a great deal of immune cells, which exacerbates clinical conditions;9,22

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increase in LDH and decrease in albumin hint cardiac and hepatic dysfunction; increases in procalcitonin
and CRP indicates bacteria co-infection. All these abnormal laboratory indexes could be used as
predictors for the severity of the COVID-19.
Glasgow Coma Scale, Sequential Organ Failure Assessment, and Acute Physiology and Chronic
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Health Evaluation II scores are commonly used in clinic to assess severity of diseases in ICU.7 In term
of patients with mild or severe illness, PSI is an important scoring system, which consisted four parts
including demographics, co-morbidity, physical examination, and laboratory, can assess the severity of
community acquired pneumonia and can be also applied to virus pneumonia.17 In our study, the severe
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group had higher PSI score than the non-severe group (p<0.001), suggesting the PSI system can be used
to evaluate the severity of the COVID-19. However, CT findings plays an important role in the diagnosis
of COVID-19, were not assessed in this scale, which may affect its accuracy.
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In our study of CT morphological features, multifocal consolidations and GGOs with interlobular
septal thickening, inferior lobes and peripheral lung distributions, were the main imaging findings in
COVID-19 as previous reports.23,24 Bilateral lung involvement was more common in the severe group
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(p=0.01); It may suggest that the extent of lesions was larger in severe cases. Pleural effusion was more
frequent in the severe group (p=0.03), consistent with previous studies that the presence of pleural
effusion on CT suggests progression of disease.25,26 In the severe group, the probability of air
bronchogram was higher, which may also indicate a larger area of GGO or consolidation.
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Semi-quantitative analysis of CT lesions can also be used to assess the severity of the disease. Kazuya
et al. analyzed pulmonary lesions in 44 patients with ARDS, and found that CT appearance has
prognostic value for prediction of mortality, number of days without mechanical ventilation, and 28-day
risk of barotrauma in patients with a clinically early stage of ARDS developed from diverse causes.27
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This result is consistent with other reports regarding prognoses of viral pneumonias such as H1N1, SARS,
and MERS.11-13 In our sturdy, we found that more pulmonary segments were involved in the severe group
(p<0.001), which indicated the extent of lesions as shown on CT may reflect the severity of lung infection
as previous studies reported.
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In recent years, the rapid development of AI has significantly improved the automatic lung
segmentation technology, making it possible to quantify the lesions automatically. Convolutional neural
networks (CNNs) have been proposed as a potential solution to problems encountered in the automatic

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 organ segmentation, which is hard to identify the lung boundary of patients with pulmonary diseases and
the distinction between lung tissue and surrounding structures.14,15 The POICT in the severe group was

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significantly higher (p<0.001), quantified by an V-Net network architecture-based automatic quantitative
CT software in this study.28 This also proves that the extent of lesions is highly correlated with the
severity of the disease. In addition, the MOICT in the severe group was significantly higher (p<0.001).
This parameter evaluates both the extent and density of the lesions, so it is a more effective assessment

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of infection than POTCT.
In our study, we demonstrated that a parsimonious model containing five features (age, LDH, CRP,
CD4+ T cell counts and MOICT) is an ideal measure to predict severity of COVID-19. This is a popular
method for regression with high dimensional data, which has been extended and broadly applied to the
Cox proportional hazard regression model for survival analysis, and to the logistic regression model for

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predicting outcome. This approach not only works better than the conventional method of choosing
predictors on the basis of the intensity of their univariate association with outcome, but it also allows
researcher to combine the selected features into a single signature. Compared to SARS’ prognostic
factors including advanced age, co-comorbidity, higher LDH levels and neutrophil counts,29 the

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underling pathophysiological mechanism of COVID-19 may be similar to that of SARS.
The LASSO logistic regression model had significantly better prediction performance than MOTCT,
POICT or PSI score (all p<0.01). This is because that the LASSO logistic regression model combines DL-
based CT quantification of lesions and clinical laboratory indicators to comprehensively assess the
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severity of the disease, unlike the other three parameters, which partially judge the patient's condition.
However, our study has several limitations. Firstly, respiratory tract specimens were used to diagnose
COVID-19 through RT-PCR. The serum of patients was not obtained to evaluate the viremia. The viral
load is a potentially useful marker associated with disease severity of coronavirus infection. Secondly,
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the proportion of the severe group was relatively lower, and there was an imbalance between the sizes of
the severe and non-severe group, which may have an impact on the statistical analysis. Thirdly, part of
enrolled patients is still hospitalized at the time of manuscript submission, and the continued follow-up
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of the disease progression is needed. Drug administration during hospitalization was not compared,
which may affect the development of the disease.
In conclusion, quantitative CT parameters and PSI score have a good performance to predict the
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severity of COVID-19. The DL-based quantitative CT model containing five clinico-radiological

features can serve as a more efficient tool in prediction. External data is needed for further validation.

Contributors
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WS and FS 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. WS, ZC, and SY
contributed to writing of the report. TL, FS, ZZ, HL, and YS revised the final manuscript. WS, MW, FL,
and XZ collected the epidemiological and clinical data. WS, XP, JZ, and YG contributed to the statistical
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analysis. All authors contributed to data acquisition, data analysis, or data interpretation, and reviewed
and approved the final version.

Declaration of interests
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We declare no competing interests.

Acknowledgments

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 We thank all our colleagues who helped us during the current study. We are also grateful to the many
front-line medical staff for their dedication in the face of this outbreak, despite the potential threat to

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their own lives and the lives of their families.

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East respiratory syndrome coronavirus. AJR Am J Roentgenol 2015; 204(4): 736-42.
rin

14. Pang T, Guo S, Zhang X, Zhao L. Automatic Lung Segmentation Based on Texture and Deep
Features of HRCT Images with Interstitial Lung Disease. Biomed Res Int 2019; 2019: 2045432.
15. Park B, Park H, Lee SM, Seo JB, Kim N. Lung Segmentation on HRCT and Volumetric CT for
Diffuse Interstitial Lung Disease Using Deep Convolutional Neural Networks. J Digit Imaging 2019;
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32(6): 1019-26.
16. China National Health Commission. Diagnosis and treatment of pneumonitis caused by new
coronavirus (trial version 5). Beijing: China National Health Commission, 2020.
http://www.nhc.gov.cn/yzygi/s7653p/202001/4294563ed35b43209b31739bd0785e67.shtml.
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17. Kao KC, Chang KW, Chan MC, et al. Predictors of survival in patients with influenza pneumonia-
related severe acute respiratory distress syndrome treated with prone positioning. Ann Intensive Care
2018; 8(1): 94.

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 18. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society:
glossary of terms for thoracic imaging. Radiology 2008; 246(3): 697-722.

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19. F Milletari NN, SA Ahmadi. V-net: Fully convolutional neural networks for volumetric medical
image segmentation. 2016 Fourth International Conference on 3D Vision (3DV); 2016. p. 565-71.
20. Jacobs C, van Rikxoort EM, Twellmann T, et al. Automatic detection of subsolid pulmonary
nodules in thoracic computed tomography images. Med Image Anal 2014; 18(2): 374-84.

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21. Song YS, Park CM, Park SJ, Lee SM, Jeon YK, Goo JM. Volume and mass doubling times of
persistent pulmonary subsolid nodules detected in patients without known malignancy. Radiology 2014;
273(1): 276-84.
22. Liu WJ, Zhao M, Liu K, et al. T-cell immunity of SARS-CoV: Implications for vaccine development
against MERS-CoV. Antiviral Res 2017; 137: 82-92.

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23. Chung M, Bernheim A, Mei X, et al. CT Imaging Features of 2019 Novel Coronavirus (2019-
nCoV). Radiology 2020: 200230.
24. Song F, Shi N, Shan F, et al. Emerging Coronavirus 2019-nCoV Pneumonia. Radiology 2020:
200274.

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25. Yuan Y, Tao XF, Shi YX, Liu SY, Chen JQ. Initial HRCT findings of novel influenza A (H1N1)
infection. Influenza Other Respir Viruses 2012; 6(6): e114-9.
26. Qureshi NR, Hien TT, Farrar J, Gleeson FV. The radiologic manifestations of H5N1 avian influenza.
J Thorac Imaging 2006; 21(4): 259-64.
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27. Ichikado K, Suga M, Muranaka H, et al. Prediction of prognosis for acute respiratory distress
syndrome with thin-section CT: validation in 44 cases. Radiology 2006; 238(1): 321-9.
28. Zhao X, Li L, Lu W, Tan S. Tumor co-segmentation in PET/CT using multi-modality fully
convolutional neural network. Phys Med Biol 2018; 64(1): 015011.
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29. Chan KS, Zheng JP, Mok YW, et al. SARS: prognosis, outcome and sequelae. Respirology 2003; 8
Suppl: S36-40.
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Table 1 Demographics and baseline characteristics of patients with COVID-19
ed
Age, years
All patients (n=196)
52 (38-65)
Severe group (n=45)
65 (54-74)

i w
Non-severe group (n=151)

e 46 (36-62)
P value
<0.001

v
Gender
Male 105 (53.6%) 30 (66.7%) 75 (49.7%)

e
0.06
Female 91 (46.4%) 15 (33.3%) 76 (50.3%)
Onset symptom to hospital admission, d
Epidemic source area exposure
Comorbidities
4 (3-8)
121 (61.7%)
72 (36.7%)

r
5 (3-8)
19 (42.2%)
25 (55.6%) r 4 (3-7.5)
102 (67.5%)
47 (31.1%)
0.35
0.003
0.004
Hypertension
Cardiovascular disease
Diabetes
46 (23.5%)
13 (6.6%)
10 (5.1%)

ee 15 (33.3%)
7 (15.6%)
2 (4.4%)
31 (20.5%)
6 (4.0%)
8 (5.3%)
0.11
0.01
1.00
Current smoking
Signs and symptoms
Fever
10 (5.1%)

170 (86.7%)

t p 3 (6.7%)

39 (86.7%)
7 (4.6%)

131 (86.8%)
0.70

1.00
Dry cough
Expectoration

n o
45 (23.0%)
35 (17.9%)
10 (22.2%)
12 (26.7%)
35 (23.2%)
23 (15.2%)
1.00
0.12

Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Table 2 Baseline laboratory findings of patients with COVID-19
ed
White blood cell count, ×10 /L
9
9
Normal range
3.5-9.5
All patients (n=196)
4.6 (3.8-5.7)
Severe group (n=45)
4.5 (3.9-6.2)

i w
Non-severe group (n=151)

e 4.7 (3.8-5.7)
P value
0.27

v
Neutrophil count, ×10 /L 1.8-6.3 2.9 (2.4-3.9) 3.5 (2.8-4.7) 2.8 (2.3-3.7) <0.001
Lymphocyte count, ×109/L 1.1-3.2 1.1 (0.8-1.4) 0.8 (0.6-1.0) 1.2 (0.9-1.5) <0.001

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D-dimer, μg/mL 0-0.5 0.4 (0.3-0.8) 0.8 (0.5-1.2) 0.4 (0.3-0.5) <0.001
Alanine aminotransferase, U/L
Aspartate aminotransferase, U/L
Lactate dehydrogenase, U/L
7-40
13-35
120-250
24 (16-36)
26 (20-35)

r
242 (204-309)
26 (19-36)
31 (26-51)
342 (290-454) r 22 (15-35)
24 (19-33)
228 (199-261)
0.07
<0.001
<0.001
Total bilirubin, μmol/L
Albumin, g/L
Serum creatinine, μmol/L
3.4-20.5
40.0-55.0
Male: 53-106

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8.2 (6.7-10.9)
40.7 (37.9-42.7)
9.0 (7.8-12.4)
37.8 (34.2-39.7)
7.9 (6.6-10.2)
41.2 (39.2-43.4)
0.02
<0.001

Increased
Serum troponin I, ng/mL
Serum myoglobin, ng/mL
Female: 44-97
0-0.040
0-48.8

t p
17 (8.7%)
0.022 (0.012-0.041)
7.3 (3.2-17.5)
6 (13.3%)
0.036 (0.019-0.062)
27.6 (8.4-63.7)
11 (7.3%)
0.019 (0.011-0.035)
5.4 (2.7-11.5)
0.23
<0.001
<0.001
Procalcitonin, ng/mL
PaO2, KPa
0-0.05
10.0-14.0

n o 0.04 (0.02-0.07)
12.2 (10.5-14.6)
0.07 (0.05-0.15)
11.1 (9.3-14.3)
0.03 (0.02-0.06)
12.5 (11.0-14.6)
<0.001
0.02

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SaO2, % 91.9-99.0 97.5 (96.2-98.5) 96.7 (94.3-98.5) 97.6 (96.6-98.5) 0.02
C-reactive protein, mg/L <3.0 15.1 (5.3-33.5) 38.7 (26.8-88.2) 11.0 (4.3-22.2) <0.001

in
CD4 T cell count, cell/μL
+
410-1590 406 (261-592) 216 (137-397) 453 (310-633) <0.001

r
Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019. PaO2 = partial pressure of oxygen. SaO2 = arterial oxygen saturation.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Table 3 Baseline CT morphological features of patients with COVID-19
ed
CT signs
NO. of pulmonary segments involved
All patients (n=196)

10（4-15）
Severe group (n=45)

15（12-18）

i ew
Non-severe group (n=151)

7（3-13.5）
P value
<0.001

v
Distribution
Bilateral lung 164 (83.7%) 43 (95.6%) 121 (80.1%) 0.01

e
Inferior lobes preference 121 (61.7%) 28 (62.2%) 93 (61.6%) 1.00
Peripheral preference
Types of pulmonary opcities
Type I
173 (88.3%)

83 (42.3%)

r
38 (84.4%)

18 (40.0%) r 135 (89.4%)

65 (43.0%)
0.43

0.73
Type II
Type III
Type IV
139 (70.9%)
140 (71.4%)
50 (25.5%)

ee 32 (71.1%)
37 (82.2%)
15 (33.3%)
107 (70.9%)
103 (68.2%)
35 (23.2%)
1.00
0.09
0.18
Internal signs
Air bronchogram
Other signs
144 (73.5%)

t p 39 (86.7%) 105 (69.5%) 0.02

Focal pulmonary fibrosis

Pleural effusion

n o
69 (35.2%)
9 (4.6%)
17 (37.8%)
5 (11.1%)
52 (34.4%)
4 (2.6%)
0.72
0.03

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Mediastinal lymphadenopathy 3 (1.5%) 2 (4.4%) 1 (0.7%) 0.13
Quantitative CT parameters

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POICT, % 3.1 (1.0-8.2) 11.1 (5.3-22.7) 2.3 (0.8-4.8) <0.001

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POCCT, % 29.8 (18.0-40.6) 32.9 (23.4-41.7) 28.9 (16.5-40.1) 0.15
MOICT, mg 64803.5 (23153.5-164271.0) 257052.0 (113596.0-456735.0) 52535.4 (19200.5-106885.5) <0.001

e p
Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019. POICT = the percentage of infection in whole lung; POCCT = the percentage of consolidation in infected regions; MOI CT = the mass of infection in whole

r
lung.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 ed
Table 4 Comparison of AUC values for LASSO regression model, MOTCT, POICT and PSI score in predicting the severity of the patients with COVID-19
Feature Evaluated
LASSO regression model
AUC Value (95% CI)
0.890 (0.833–0.947)
Cutoff Value
−1.238
Sensitivity (%)
82.2
Specificity (%)
82.8
PPV (%)
58.7

i ew
NPV (%)
94.0
Accuracy (%)
82.7
P value

0.002a

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MOTCT 0.813 (0.732–0.894) 107720.0 80.0 75.5 49.3 92.7 76.5
POICT 0.805 (0.724–0.886) 5.9% 73.7 78.8 50.8 90.8 77.6 <0.001b

e
PSI score 0.751 (0.668–0.833) 63.5 60.0 81.5 49.1 87.2 76.5 <0.001c

r r
COVID-19 = Corona Virus Disease 2019. PPV = positive predictive value. NPV = negative predictive value. POICT = the percentage of infection in whole lung. MOICT = the
mass of infection in whole lung. PSI = pneumonia severity index. a, b, and c, The ROC curve for the LASSO logistic regression model showed significant superiority as
compared with MOTCT, POICT and PSI score, respectively.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 ed
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Figure 1: the opacity category of COVID-19 pneumonia
A: type I, pure ground-glass opacities (pGGOs), which manifested as a hazy opacity without obscuring the underlying pulmonary parenchyma; B: type II, GGOs with

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consolidation, which was defined as pGGOs with the area of consolidation obscuring the underlying pulmonary parenchyma; C: GGOs with interlobular septal thickening or
reticulation as crazy-paving sign; type III, D: type IV, the consolidation, which was defined as the lesions obscuring the underlying pulmonary parenchyma.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
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Figure 2: The network is a V-shaped structure with a contracting path that extracts global image features and an expansive path that integrates fine-grained image features，

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which is combined with the bottle-neck structure for improving segmentation speed.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 ed
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Figure 3: A fifty-seven years old female (sever group); the onset symptoms were fever and cough; CT showed GGO, GGO with consolidation and GGO with interlobular septal
thickening were widely distributed (A). The quantitative volume rending CT (B) showed the GGO with large-scale consolidation widely distributed. (The red zone indicated

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consolidation, yellow indicated GGO with consolidation, green indicated GGO, while the blue zone indicated normal pulmonary parenchyma and white indicated trachea.)

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
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Figure 4: A fifty-five years old male (non-sever group); the onset symptoms were fever, dry pharynx and fatigue; CT showed GGO, GGO with consolidation were
distributed peripherally (A). The quantitative volume rending CT (B) showed the GGO-based lesions mainly located in the left upper lobe and right lower lobe. (The

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red zone indicated consolidation, yellow indicated GGO with consolidation, green indicated GGO, while the blue zone indicated normal pulmonary parenchyma and
white indicated trachea.)

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
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Figure 5: The clinico-radiological feature selection using LASSO regression model. A: Optimal feature selection according to AUC value; B: LASSO coefficient profiles of
the 24 clinico-radiological features. Vertical line was drawn at the selected value using 10-fold cross-validation, where optimal λ resulted in 5 non-zero coefficients.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
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Figure 6: The ability of LASSO logistic regression model, MOICT, POICT and PSI score to predict the severity of COVID-19 were compared by Delong test, with the AUC
values of 0.890, 0.813, 0.805, and 0.751, respectively. The LASSO logistic regression model had significantly better prediction performance than other three parameters
(p=0.002, p<0.001, and p<0.001, respectively). POICT = the percentage of infection in whole lung. MOICT = the mass of infection in whole lung. PSI = pneumonia severity
index.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Click here to download Figure Fig 1.tif

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Figure 1 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Click here to download Figure Fig 2.tif

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Figure 2 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Click here to download Figure Fig 3.tif

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Figure 3 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Click here to download Figure Fig 4.tif

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Figure 4 This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Figure 5 Click here to download Figure Fig 5.tif

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Figure 6 Click here to download Figure Fig 6.tif

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
Table

Table 1 Demographics and baseline characteristics of patients with COVID-19

ed
Age, years
All patients (n=196)
52 (38-65)
Severe group (n=45)
65 (54-74)

i w
Non-severe group (n=151)

e 46 (36-62)
P value
<0.001

v
Gender
Male 105 (53.6%) 30 (66.7%) 75 (49.7%)

e
0.06
Female 91 (46.4%) 15 (33.3%) 76 (50.3%)
Onset symptom to hospital admission, d
Epidemic source area exposure
Comorbidities
4 (3-8)
121 (61.7%)
72 (36.7%)

r
5 (3-8)
19 (42.2%)
25 (55.6%) r 4 (3-7.5)
102 (67.5%)
47 (31.1%)
0.35
0.003
0.004
Hypertension
Cardiovascular disease
Diabetes
46 (23.5%)
13 (6.6%)
10 (5.1%)

ee 15 (33.3%)
7 (15.6%)
2 (4.4%)
31 (20.5%)
6 (4.0%)
8 (5.3%)
0.11
0.01
1.00
Current smoking
Signs and symptoms
Fever
10 (5.1%)

170 (86.7%)

t p 3 (6.7%)

39 (86.7%)
7 (4.6%)

131 (86.8%)
0.70

1.00
Dry cough
Expectoration

n o
45 (23.0%)
35 (17.9%)
10 (22.2%)
12 (26.7%)
35 (23.2%)
23 (15.2%)
1.00
0.12

Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Table 2 Baseline laboratory findings of patients with COVID-19
ed
White blood cell count, ×10 /L
9
9
Normal range
3.5-9.5
All patients (n=196)
4.6 (3.8-5.7)
Severe group (n=45)
4.5 (3.9-6.2)

i w
Non-severe group (n=151)

e 4.7 (3.8-5.7)
P value
0.27

v
Neutrophil count, ×10 /L 1.8-6.3 2.9 (2.4-3.9) 3.5 (2.8-4.7) 2.8 (2.3-3.7) <0.001
Lymphocyte count, ×109/L 1.1-3.2 1.1 (0.8-1.4) 0.8 (0.6-1.0) 1.2 (0.9-1.5) <0.001

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D-dimer, μg/mL 0-0.5 0.4 (0.3-0.8) 0.8 (0.5-1.2) 0.4 (0.3-0.5) <0.001
Alanine aminotransferase, U/L
Aspartate aminotransferase, U/L
Lactate dehydrogenase, U/L
7-40
13-35
120-250
24 (16-36)
26 (20-35)

r
242 (204-309)
26 (19-36)
31 (26-51)
342 (290-454) r 22 (15-35)
24 (19-33)
228 (199-261)
0.07
<0.001
<0.001
Total bilirubin, μmol/L
Albumin, g/L
Serum creatinine, μmol/L
3.4-20.5
40.0-55.0
Male: 53-106

ee
8.2 (6.7-10.9)
40.7 (37.9-42.7)
9.0 (7.8-12.4)
37.8 (34.2-39.7)
7.9 (6.6-10.2)
41.2 (39.2-43.4)
0.02
<0.001

Increased
Serum troponin I, ng/mL
Serum myoglobin, ng/mL
Female: 44-97
0-0.040
0-48.8

t p
17 (8.7%)
0.022 (0.012-0.041)
7.3 (3.2-17.5)
6 (13.3%)
0.036 (0.019-0.062)
27.6 (8.4-63.7)
11 (7.3%)
0.019 (0.011-0.035)
5.4 (2.7-11.5)
0.23
<0.001
<0.001
Procalcitonin, ng/mL
PaO2, KPa
0-0.05
10.0-14.0

n o 0.04 (0.02-0.07)
12.2 (10.5-14.6)
0.07 (0.05-0.15)
11.1 (9.3-14.3)
0.03 (0.02-0.06)
12.5 (11.0-14.6)
<0.001
0.02

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SaO2, % 91.9-99.0 97.5 (96.2-98.5) 96.7 (94.3-98.5) 97.6 (96.6-98.5) 0.02
C-reactive protein, mg/L <3.0 15.1 (5.3-33.5) 38.7 (26.8-88.2) 11.0 (4.3-22.2) <0.001

in
CD4 T cell count, cell/μL
+
410-1590 406 (261-592) 216 (137-397) 453 (310-633) <0.001

r
Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019. PaO2 = partial pressure of oxygen. SaO2 = arterial oxygen saturation.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 Table 3 Baseline CT morphological features of patients with COVID-19
ed
CT signs
NO. of pulmonary segments involved
All patients (n=196)

10（4-15）
Severe group (n=45)

15（12-18）

i ew
Non-severe group (n=151)

7（3-13.5）
P value
<0.001

v
Distribution
Bilateral lung 164 (83.7%) 43 (95.6%) 121 (80.1%) 0.01

e
Inferior lobes preference 121 (61.7%) 28 (62.2%) 93 (61.6%) 1.00
Peripheral preference
Types of pulmonary opcities
Type I
173 (88.3%)

83 (42.3%)

r
38 (84.4%)

18 (40.0%) r 135 (89.4%)

65 (43.0%)
0.43

0.73
Type II
Type III
Type IV
139 (70.9%)
140 (71.4%)
50 (25.5%)

ee 32 (71.1%)
37 (82.2%)
15 (33.3%)
107 (70.9%)
103 (68.2%)
35 (23.2%)
1.00
0.09
0.18
Internal signs
Air bronchogram
Other signs
144 (73.5%)

t p 39 (86.7%) 105 (69.5%) 0.02

Focal pulmonary fibrosis

Pleural effusion

n o
69 (35.2%)
9 (4.6%)
17 (37.8%)
5 (11.1%)
52 (34.4%)
4 (2.6%)
0.72
0.03

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Mediastinal lymphadenopathy 3 (1.5%) 2 (4.4%) 1 (0.7%) 0.13
Quantitative CT parameters

in
POICT, % 3.1 (1.0-8.2) 11.1 (5.3-22.7) 2.3 (0.8-4.8) <0.001

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POCCT, % 29.8 (18.0-40.6) 32.9 (23.4-41.7) 28.9 (16.5-40.1) 0.15
MOICT, mg 64803.5 (23153.5-164271.0) 257052.0 (113596.0-456735.0) 52535.4 (19200.5-106885.5) <0.001

e p
Data are median (IQR) or n (%). P values comparing the severe group and non- severe group are from Fisher’s exact test, or Wilcoxon rank-sum test. COVID-19 = Corona
Virus Disease 2019. POICT = the percentage of infection in whole lung; POCCT = the percentage of consolidation in infected regions; MOI CT = the mass of infection in whole

r
lung.

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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089
 ed
Table 4 Comparison of AUC values for LASSO regression model, MOTCT, POICT and PSI score in predicting the severity of the patients with COVID-19
Feature Evaluated
LASSO regression model
AUC Value (95% CI)
0.890 (0.833–0.947)
Cutoff Value
−1.238
Sensitivity (%)
82.2
Specificity (%)
82.8
PPV (%)
58.7

i ew
NPV (%)
94.0
Accuracy (%)
82.7
P value

0.002a

v
MOTCT 0.813 (0.732–0.894) 107720.0 80.0 75.5 49.3 92.7 76.5
POICT 0.805 (0.724–0.886) 5.9% 73.7 78.8 50.8 90.8 77.6 <0.001b

e
PSI score 0.751 (0.668–0.833) 63.5 60.0 81.5 49.1 87.2 76.5 <0.001c

r r
COVID-19 = Corona Virus Disease 2019. PPV = positive predictive value. NPV = negative predictive value. POICT = the percentage of infection in whole lung. MOICT = the
mass of infection in whole lung. PSI = pneumonia severity index. a, b, and c, The ROC curve for the LASSO logistic regression model showed significant superiority as
compared with MOTCT, POICT and PSI score, respectively.

ee
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n o
in t
p r
r e
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This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3546089