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\begin{document}

\title{CT Diagnosis of COVID-19 Based on the Imaging Signs of Secondary
Pulmonary Lobular}



\author[1]{deli zhao}%
\author[1]{guokun wang}%
\author[1]{peng chen}%
\author[1]{Shanshan Yu}%
\author[1]{Haibo Wang}%
\author[1]{Xin Wang}%
\author[2]{jinling zhang}%
\affil[1]{Affiliation not available}%
\affil[2]{Harbin Medical University}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objectives To study the CT diagnosis of COVID-19 that was based on the
imaging features of secondary pulmonary lobular structure. Materials and
methods After institutional review board approval and informed consent,
139 cases with suspected COVID-19 who undergone CT were retrospectively
analyzed. Based on the anatomical structure of pulmonary lobule, the
imaging features of secondary pulmonary lobular structure on CT images
was defined and built simulation diagrams serve as a unified standard.
The imaging performance of confirmed 103 cases was evaluated for
diagnosis of COVID-19. Results Of these 139 cases, 103 cases were
confirmed for COVID-19, 36 cases were confirmed for other diseases.The
sensitivity, specificity and accuracy of CT are 83.33\%, 20.39\%,
80.58\%,Of the 103 COVID-19 cases, 82(79.61\%) cases were typical cases
and 21(20.39\%)cases were atypical cases. 65(63.11\% ) cases were in
the early or advanced stage, 26(25.24\%) cases were in the severe or
recovery stage, and 12(11.65\%)were in multiple stages. The scores of
pulmonary lobular structure in typical COVID-19 (3.42\selectlanguage{ngerman}±1.25) were
significant different compared with atypical COVID-19 (1.51±1.34,
P\textless{}0.001). The inter-observer agreement for the score of
secondary pulmonary lobular structure was excellent (kappa = 0.863,
P\textless{}0.05). Conclusion To recognize the CT common imaging signs
of secondary pulmonary lobular structure in COVID-19 can deepen the
understanding of COVID-19 from the basis of image anatomy, and screen
suspected cases and provide imaging basis for diagnosis and differential
diagnosis.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{INTRODUCTION}

According to the latest guidelines for diagnosis and treatment of
COVID-19(Novel coronavirus pneumonia) by the General Office of the
National Health Commission of China, the use of fluorescent
RT-PCR(reverse transcriptase polymerase chain reaction) to detect
nucleic acids of the coronavirus is the gold standard for molecular
diagnosis of COVID-19(1,2), but nucleic acid detection has several
limitations, including the need for high specificity of primer sets, low
sensitivity, and the length of testing period. In comparison,
CT(Computed tomography) imaging offers a simple, fast, and highly
sensitive means to elucidate the extent and nature of lung tissue in
COVID-19. After analyzing the CT images of confirmed COVID-19, we
noticed that the signs of secondary pulmonary lobular structures were
commonly associated with all stages of COVID-19. Recognizing the
underlying secondary pulmonary lobular structural image signs can enable
us to understand the typical or atypical CT characteristics of COVID-19,
so as to provide reliable imaging diagnosis and differential diagnosis
for clinical early diagnosis and prognosis judgment(3).

\textbf{MATERIALS AND METHODS}

\textbf{Population and CT image data acquisition}

We retrospectively reviewed 139 cases that were collected from January
26 to February 10, 2020.Among them, 103 patients were confirmed as
COVID-19 patients by nose or throat swab sampling. The data
characteristics of all patients are shown in Table 1.Patients were
examined using the conventional CT(16-slice or 64-slice CT) machines.
Scanning parameters and tube voltage were set to automatic mode for
chest. Images were reconstructed using the best electronic voltage
measured, with 5 millimeter slice thickness, and 5 millimeter slice
interval. This study is approved by our Institutional Review Board,
which is waived the requirement for patients' informed consent referring
to the CIOMS guideline.

\textbf{CT images analysis}

\textbf{Classification of secondary pulmonary lobular structural imaging
signs}

To define the imaging features of secondary pulmonary lobular structure
on CT images, then building simulation schematics to strengthen
cognition and serve as a unified standard for evaluation (Fig.1, 2). The
secondary pulmonary lobular structural imaging signs are defined as a
set of CT imaging of pulmonary lobules and its related structures, which
are typified by five major categories: I Lobular size sign, II Fusion
lobular sign, III interlobular septal thickening sign, IV intralobular
interstitial thickening sign, V intralobular vascular thickening sign
(Fig. 2).

\textbf{Definition of typical CT features of COVID-19}

Combined with the typical imaging diagnostic standards of COVID-19 that
were reported by domestic imaging diagnosis guidelines and some
literatures (16-18), We define the cases with the following three CT
features as typical COVID-19 cases and the others as atypical cases in
this study . These three features are as follows: Firstly, density:
Multiple GGOs(Ground glass nodules) or consolidations are present.
Secondly, size: Pulmonary lobular or fusion lobule. Thirdly,
distribution: Subpleural distribution with major axis nearly parallel to
pleura and perpendicular to the bronchovascular bundle.

\textbf{Score standard for evaluation secondary pulmonary lobular
structure}

\textbf{Secondary} pulmonary lobular structure scores for all confirmed
cases which include lobular size sign (1 score), fusion lobular sign (1
score), interlobular septal thickening sign (1 score), intralobular
interstitial thickening sign (1 score) and intralobular vascular
thickening sign (1 score).Two senior radiologists with more than 10
years of experience each independently based on the imaging signs of
secondary pulmonary lobular structure and assessed all the cases which
include confirmed cases of COVID-19 (typical,atypical and multi-stage )
and confirmed cases of non-COVID-19.

\textbf{Statistic analysis}

Statistical analyses were performed with the SPSS software (version
22.0, IBM).Count index was presented as percentage, and all data were
presented as means and standard deviation (mean\selectlanguage{ngerman}±SD). Independent sample
t-test or Chi square test was used. Inter-observer agreement for the
subjective image quality was estimate using kappa statistic. P
\textless{}0.05 was considered statistically significant.

\textbf{RESULTS}

Of these 139 cases, 103 cases were confirmed for COVID-19 and 36cases
were confirmed other diseases(including other pneumonia, pulmonary
hemorrhage, pulmonary edema and traumatic wet lung). The sensitivity,
specificity and accuracy of CT are 83.33\%, 20.39\%, 80.58\%, Of the 103
COVID-19 cases, 82(79.61\%) cases were typical cases and
21(20.39\%\selectlanguage{english})cases were atypical cases. 65(63.11\% ) cases were in the
early or advanced stage, 26(25.24\%) cases were in the severe or
recovery stage, and 12(11.65\%)were in multiple stages. Two radiologists
scored the imaging signs of secondary pulmonary lobular structure of
COVID-19 and other diseases. By comparing the image features of typical
cases and atypical cases, there was statistical difference between the
size \textless{}3cm, the density of GGO and consolidation, but there was
no statistical difference between the size \textgreater{} 3cm and the
density of mixed GGO, there is significant statistical difference
between typical cases and atypical cases of distribution and location.
The scores of secondary pulmonary lobular structure in typical COVID-19
(3.42+-1.25) were significant different compared with atypical COVID-19
(1.51+-1.34, P\textless{}0.001). The inter-observer agreement for the
score of secondary pulmonary lobular structure was excellent (kappa =
0.863, P\textless{}0.05). The diagnosis of typical CT features (Fig. 3)
and atypical CT features (Fig. 4) in COVID-19 are shown in table 2.The
evaluation results of dynamic multi-stage images (Fig. 5) and
differential diagnosis with non- COVID-19(Fig. 6) based on the image
signs of secondary pulmonary lobular structure are shown in and table 3.

\textbf{DISCUSSION}

\textbf{Secondary} pulmonary is the basic unit of pulmonary anatomic
function, which has been playing an important role in
HRCT(High-resolution computed tomography). The imaging features of
secondary pulmonary lobular structure run through all stages of the
image performance of COVID-19. According to the anatomical differences
of pulmonary lobules, Fleischner and Heitzman proposed that the lung can
be divided into peripheral pulmonary cortex and central pulmonary
medulla(4,5). Webb put forward the concept of cortical lobule,
highlighting the anatomical characteristics of pulmonary cortical
lobule. The characteristics of the pulmonary cortical lobule also lay
the anatomical basis for the distribution of COVID-19 under the pleura
(6,7).Therefore, it is critical to discern the characteristics of
lobules and their distribution for accurate diagnosis of COVID-19.

The CT features of viral pneumonia, such as lobular size, fusion lobule,
thickening of intralobular interstitium and interlobular septum, that
have been respectively reported in the related literatures of influenza
and SARS(Severe acute respiratory syndrome)\selectlanguage{english}(8-12\selectlanguage{english}). In particular,
COVID-19 has a virus homology with SARS. The image of COVID-19 is highly
similar to the lobular image feature reported by SARS\selectlanguage{english}(13-16\selectlanguage{english}).
Therefore, the evaluation method and scoring standard of five categories
of secondary pulmonary lobular structure image based on the anatomical
structure of secondary pulmonary lobule were proposed for the first time
in this study. The lobular size sign in COVID-19 often shows GGO or
consolidation of 1-3centimeters, which is consistent with the results of
the lobular size of SARS by Wong. (13). The fusion lobular sign is
defined as the shape of wedge-shaped, fan-shaped, irregular or bat wing
with the size between 3 centimeters and lung lobe, which does not follow
the lung segments or lobe. In the early stage, the interlobular septal
thickening sign is generally not obvious, only to make the edge of the
lesion clearer, and transit to grid shape in the advanced or the
recovery stage. The interlobular interstitial thickening sign likes
``paving stone sign'' which is very characteristic, and is very specific
in the diagnosis of COVID-19. The interlobular vascular thickening sign
is more common in the peripheral pulmonary cortex lobular blood vessels,
particularly in the early stage of COVID-19.

From the perspective of image thinking, CT images of different types
COVID-19 mainly include typical and atypical CT features, and the
evaluation of dynamic stages. In this study, combined with the typical
imaging diagnostic standards of COVID-19 that were reported by domestic
imaging diagnosis guidelines and some literatures (16-18), as well as a
summary of 103 confirmed cases, 82(79.61\%) single-stage and 12(11.65\%)
multi-stage cases of the typical COVID-19 have three characteristics.
These three typical performances of COVID-19 are consistent with some
reports (19-21), but the ideas and concerns of authors are based on the
image signs of secondary pulmonary lobular structure, and the analysis
from density, size and distribution is more in line with the traditional
image thinking mode. As a new infectious disease, COVID-19 has not been
fully recognized so far. In our study, we found that the image
manifestations of atypical cases are mostly GGO or consolidation,
including single or mixed GGO, thickening of bronchovascular bundle with
peripheral GGO, mixed GGO in lobes or segments, and halo sign or anti
halo sign in a few cases. These findings are consistent with the
relevant literature (20-22).

In this study, there are two types of differential diagnosis of
COVID-19: infectious disease(other viral pneumonia, bacterial pneumonia,
mycoplasma infection, cryptogenic organizing pneumonia, eosinophilic
pneumonia) and non-infectious disease(pulmonary hemorrhage, pulmonary
edema and traumatic wet lung). To some extent, the imaging
manifestations of these diseases may overlap with COVID-19, so it is
great significance to combine the imaging signs of secondary pulmonary
lobular structure for differential diagnosis between COVID-19 and
non-COVID-19. However, there are some limitations in this study:Firstly,
there are few cases of non-COVID -19, resulting in partial statistical
results bias.Secondly, there is no differential diagnosis between
COVID-19 and other relatively certain diseases.Thirdly, in COVID-19
cases, the correlation between secondary pulmonary lobular structural
signs and related laboratory indicators was not studied, such as
C-reactive protein. This is also the research direction of the next step
after increasing the number of samples.

\textbf{CONCLUSION}

In this study we found that recognize the common imaging signs of
secondary pulmonary lobular structure in COVID-19 can deepen the
understanding of COVID-19 from the basis of image anatomy, and provide
reliable imaging diagnosis and differential diagnosis basis for early
clinical diagnosis.

\textbf{References}

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\textbf{Tables}

\textbf{Table 1. Comparison baseline characteristics between COVID-19
cases with non-COVID-19 cases}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Characteristic & COVID-19 (n=103) & Non-COVID-19 (n=36) & P
Value\tabularnewline
Mean age(y) & 47.3 \selectlanguage{ngerman}± 12.5 & 42.5 \selectlanguage{ngerman}±13.2 & 0.792\tabularnewline
Sex & & &\tabularnewline
Male(n) & 63(61.17\%) & 25(69.44\%) & 0.375\tabularnewline
Female(n) & 40(38.83\%) & 11(30.56\%) &\tabularnewline
Symptom and signs & & &\tabularnewline
Pharyngeal discomfort & 10(9.71\%) & 2(5.56\%) & 0.675\tabularnewline
Fever & 85(82.52\%) & 9(25.00\%) & \textless{}0.0001\tabularnewline
Cough & 66(64.08\%) & 17(47.22\%) & 0.076\tabularnewline
Abdominal pain & 12(11.65\%) & 0 & 0.036\tabularnewline
Temperature(\textgreater{}37.3) & 98(95.15\%) & 26(72.22\%) &
0.001\tabularnewline
White blood cell count (\selectlanguage{ngerman}×10 9 /L) & & &\tabularnewline
Normal/decreased & 85(82.52\%) & 22(61.11\%) & 0.009\tabularnewline
Increased & 18(17.48\%) & 14(38.89\%) &\tabularnewline
C-reactive protein (mg/L) increased & 87(84.47\%) & 19(52.78\%) &
0.0001\tabularnewline
\bottomrule
\end{longtable}

Note: Date in parentheses is number of cases. Data are n (\%), mean
(SD), p\textless{}0.05. Increased means over the upper limit of the
normal range and decreased means below the lower limit of the normal
range.

\textbf{Table 2. Comparison CT image characteristics between typical
cases with atypical cases in COVID-19}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Characteristic & Typical (n=82) & Atypical (n=21) & P
Value\tabularnewline
Size & & &\tabularnewline
Small nodule (\textless{}1cm) & 2(2.44\%) & 5(23.81\%) &
0.003\tabularnewline
Lobule (1 to 3cm) & 38(46.34\%) & 3(14.29\%) & 0.007\tabularnewline
3cm to lobe & 42(51.22\%) & 13(61.90\%) & 0.381\tabularnewline
Distribution and location & & &\tabularnewline
Focal & 0 & 9(42.86\%) & \textless{}0.01\tabularnewline
Multi-focal/diffuse & 82 & 12(57.14\%) & \textless{}0.01\tabularnewline
Airway & 0 & 7(58.33\%) & \textless{}0.01\tabularnewline
Subpleural & 82 & 0 & \textless{}0.01\tabularnewline
Segmental/lobe & 0 & 5(41.67\%) & \textless{}0.01\tabularnewline
Density & & &\tabularnewline
Pure-GGO & 43(52.44\%) & 4(19.05\%) & 0.006\tabularnewline
Mix-GGO & 28(34.15\%) & 9(42.86\%) & 0.458\tabularnewline
Consolidation & 11(13.41\%) & 8(38.10\%) & 0.009\tabularnewline
Lobular structure scores & 3.42\selectlanguage{ngerman}±1.25 & 1.51\selectlanguage{ngerman}±1.34 &
\textless{}0.0001\tabularnewline
\bottomrule
\end{longtable}

Note: Number in parentheses are percentages, Data are n (\%), mean (SD),
p\textless{}0.05.

\textbf{Table 3. Evaluation of imaging features of pulmonary lobular
structure between COVID-19 and non- COVID-19}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Characteristic\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Lobular size sign\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Fusion lobular sign\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Interlobular septal thickening\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Intralobular vascular thickening\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Intralobular interstitial thickening\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{COVID-19}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Single stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Multi-stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Early stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Advanced Stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Severe stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Recovery stage\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
++\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Non- COVID-19\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
+\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\ldots{}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Note: Plus signs indicate the relative frequency of the findings from
lowest(+) to higest(+++);shot signs indicate no findings in this study.

\textbf{Figure Legend}

\textbf{Note} In order to facilitate the reader's recognition of
pulmonary lobular signs, different arrows in figure2-6 in this
manuscript represent the different signs (green arrow shows lobular size
sign, green double-headed arrow shows fusion lobular sign, black arrow
shows lobular septal thickening, white arrow shows lobular interstitial
thickening sign , red arrow shows lobular vascular thickening sign).

\textbf{Figure 1} Schematic of lobular structure of axial CT. The
reticular structure of the left mimics the distribution of pulmonary
lobules, and the larger one is the cortex lobule and the smaller one is
the medullary lobule. The right is an enlarged simulated lobular
structure. Letter a refers to the interlobular septum, b refers to
intralobular vessel, and c refers to the intralobular interstitium.

\textbf{Figure 2} Schematics~of the lobular structural characteristics
that include five categories: Lobular size (a), fusion lobules (b),
interlobular septal thickening (c), intralobular interstitial~thickening
(d), intralobular vascular thickening (e). a1-e1images are the actual CT
axial images corresponding to the schematics.

\textbf{Figure 3} The combined picture (a-f) is composed of typical
cases of COVID-19. All the cases are consistent with the three
characteristics which include multiple GGOs or consolidations ,
pulmonary lobular or fusion lobule size and subpleural distribution.

\textbf{Figure 4} Six COVID-19 cases are selected to represent the five
atypical CT features. a-b represent single GGO or consolidation, c-d
represent halo sign or reverse-halo sign, e-f represent bronchovascular
bundle thickening with peripheral GGO or consolidation.

\textbf{Figures 5 a-c} Early, advanced and recovery stages of one
COVID-19 patient are shown. a. The size of the lobule in the early
stage. b. Fusion lobules in the advanced stage. The intralobular
interstitial and interlobular vascular thickened. c. Lobular septal
thickening in the recovery stage. \textbf{d-f.} Advanced, severe and
recovery stages of another COVID-19 patient are depicted. d. During the
advanced stage, the area of right pulmonary fusion lobule is increased,
and the new leisons with lobular size are seen in the left lung. e.
Diffuse mosaic sign (``white lung'') in severe stage. f. The
interlobular septal thickening in the recovery stage.

\textbf{Figure 6} a-f are differential diseases with COVID-19 in CT
imaging respectively. Lobar pneumonia(a) is characterized by
consolidation of lobar segments without obvious pulmonary lobular
structure signs. Mycoplasma pneumonia (b) and Influenza pneumonia(c),
both of them can be seen the sign of fusion lobule, but the mycoplasma
pneumonia is distributed along the bronchovascular bundle. Pulmonary
edema (d), there is obvious sign of interlobular septal thickening. Both
traumatic wet lung (e) and pulmonary hemorrhage (f) show subpleural GGO,
but there is no significant pulmonary lobular structure signs.

\textbf{Hosted file}

\verb`Response to Reviewers.doc`  available at \url{https://authorea.com/users/316988/articles/457734-ct-diagnosis-of-covid-19-based-on-the-imaging-signs-of-secondary-pulmonary-lobular}\selectlanguage{english}
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