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\begin{document}

\title{Chest CT signs associated with pejorative evolution in COVID-19 patients}



\author[1]{Romain Auger}%
\author[2]{Paul-Armand  Dujardin }%
\author[1]{Aurore Bleuzen }%
\author[1]{Juliette Buraschi }%
\author[1]{Natacha Mandine }%
\author[1]{Sylvain  Marchand-Adam }%
\author[1]{Arthur  Pearson }%
\author[1]{Gaëlle  Derot }%
\affil[1]{CHRU Tours}%
\affil[2]{CHU Tours}%


\vspace{-1em}



  
  \date{May 30, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background COVID-19 is a complex virus that has been spreading since
December 2019. In this study, we aimed to assess the association between
chest Computed Tomography (CT) signs and pejorative evolution, such as
death, use of invasive endotracheal ventilation (IEV) and intensive care
unit hospitalization (ICUH). We also evaluated the diagnostic
performance of chest CT versus the diagnostic gold standard, RT-PCR.
Methods This retrospective monocentric study included 349 patients who
had a chest CT either for clinical suspicion of COVID-19 pneumonia with
severe initial symptoms, or clinical deterioration in patients with
suspected COVID-19 pneumonia, or clinical deterioration in RT-PCR
positive patients. Principal judgement criteria for pejorative evolution
were: death, IEV, and ICUH. Results Among the 109 RT-PCR positive
patients, there were higher rates of bronchial distortion and total
volume lung involvement [?] 50\% in the dead, IEV and ICUH groups (p
\textless{} 10-3). Vascular dilatation and a number of involved lobes [?]
4 were associated with IEV and ICUH (p \textless{} 10-3). Among the 349
patients, sensitivity, specificity, positive and negative predictive
values of chest CT versus RT-PCR were respectively 93,6 \% {[}95\% CI
89-98,2{]}, 85,8 \% {[}81,4-90,2{]}, 75 \% {[}67,7-82,3{]}, and 96,7 \%
{[}94,3-99,1{]}. Unlike previous studies, we found different kinds of CT
signs patterns, rather than a stereotyped COVID-19 pneumonia pattern.
Maximal lesion expansion was observed during the second week after the
first symptoms. Conclusion Bronchial distorsion and lesion expansion
seem to be correlated with death in COVID-19 patients. This study
confirms chest CT major diagnostic value.%
\end{abstract}%



\sloppy


\textbf{Title :} Chest CT signs associated with pejorative evolution in
COVID-19 patients

\textbf{Short title} : Chest CT prognostic value in COVID-19 patients

\textbf{Author list}

Romain Auger\textsuperscript{1}, Paul-Armand
Dujardin\textsuperscript{2}, Aurore Bleuzen\textsuperscript{1}, Juliette
Buraschi\textsuperscript{1}, Natacha Mandine\textsuperscript{1}, Sylvain
Marchand-Adam\textsuperscript{3}, Arthur Pearson\textsuperscript{1}, and
Ga\selectlanguage{ngerman}ëlle Derot\textsuperscript{1}

\textsuperscript{1} Department of Radiology, CHRU Tours, France

\textsuperscript{2} CIC 1415, CHU Tours, Inserm, Tours Cedex,
France\textsuperscript{3} Department of Respiratory Medecine, CHRU
Tours, France

\textbf{Corresponding author}

\emph{romain.auger100@gmail.com}

Orcid ID~: 0000-0003-3927-7923

Department of Radiology, CHRU Tours, 2 Boulevard Tonnellé, 37000 Tours
cedex 9, France

\textbf{Acknowledgments}

\textbf{Author contributions}

The study was designed by RA, GD and P-AD. Data collection and analysis
was performed by RA and GD. Statistical analysis was performed by P-AD
and RA. First draft of the manuscript was written by RA, and all authors
commented on previous versions of the manuscript. All authors have read
and approved the final manuscript.

\textbf{Abstract}

\textbf{Background}

COVID-19 is a complex virus that has been spreading since December 2019.
In this study, we aimed to assess~the association between chest Computed
Tomography (CT) signs and~pejorative evolution, such~as death, use of
invasive endotracheal ventilation (IEV) and intensive care unit
hospitalization (ICUH). We also evaluated the diagnostic performance of
chest CT versus the diagnostic gold standard, RT-PCR.

\textbf{Methods}

This retrospective monocentric study included 349 patients who had a
chest CT either for clinical suspicion of COVID-19 pneumonia with severe
initial symptoms,~or clinical deterioration~in patients with
suspected~COVID-19 pneumonia, or clinical deterioration~in RT-PCR
positive patients.~ Principal judgement criteria for pejorative
evolution were: death, IEV, and ICUH.

\textbf{Results~}

Among~the~109 RT-PCR positive patients, there were higher rates of
bronchial distortion and total volume lung involvement \selectlanguage{english}[?] 50\% in the
dead, IEV and ICUH groups (p \textless{} 10\textsuperscript{-3}).
Vascular dilatation and a number of involved lobes \selectlanguage{english}[?] 4 were associated
with IEV and ICUH (p \textless{} 10\textsuperscript{-3}).

Among the 349 patients,~sensitivity, specificity, positive and
negative~predictive~values of~chest~CT~versus RT-PCR~were~respectively
93,6 \% {[}95\% CI 89-98,2{]}, 85,8 \% {[}81,4-90,2{]}, 75 \%
{[}67,7-82,3{]}, and 96,7 \% {[}94,3-99,1{]}.

Unlike previous studies, we found different~kinds of CT signs
patterns,~rather than a stereotyped COVID-19 pneumonia pattern. Maximal
lesion~expansion was observed during the second week after the first
symptoms.

\textbf{Conclusion}Bronchial distorsion and lesion expansion seem to be
correlated with death in COVID-19 patients. This study confirms chest CT
major diagnostic value.

\textbf{Keywords} ~: COVID-19, chest CT, invasive endotracheal
ventilation, bronchial distortion, critical care.

\textbf{Introduction}

Coronavirus disease (COVID-19) has been spreading worldwide since
December 2019 from Wuhan, Hubei Province.\textsuperscript{1} The virus
called SARS-Cov-2 belongs to the Betacoronavirus genus, is composed of a
positive single-stranded RNA, and has a 50-200 nm
diameter.\textsuperscript{2,3} Bats are the natural reservoir for
coronaviruses.\textsuperscript{4} On April 26\textsuperscript{th} 2020,
more than 2~355~853 cases (of which 947~693 in Europe) and 164~656
deaths worldwide were reported due to this
pandemic.\textsuperscript{5}On March 16\textsuperscript{th} 2020 in
France, 124~114 cases were confirmed with 22~614 deaths (i.e. 18,6 \% of
mortality).\textsuperscript{6} Fever, cough, fatigue, diarrhoea,
dyspnoea and myalgia are the most common symptoms but the patients'
condition can deteriorate rapidly, requiring intensive medical
care.\textsuperscript{7,8}Real time reverse-transcription polymerase
chain reaction (RT-PCR) is the standard reference to detect viral
nucleic acid but false-negative results have been reported and have led
to a 66-80 \% sensitivity due to multiple factors, notably the quality
of sampling.\textsuperscript{9}Compared to RT-PCR, chest computed
tomography (CT) is an easy-to-use and a faster method to diagnose and
assess an early pulmonary COVID-19 infection.\textsuperscript{10} Chest
CT can also help to monitor the evolution and diagnose complications of
COVID-19. Indeed, some authors have demonstrated the diagnostic value of
chest CT in COVID-19 pneumonia describing compatible radiological
signs.\textsuperscript{11--13} Ai.\emph{et al.} have evaluated chest CT
diagnostic value in 1014 cases of suspected COVID-19 using RT-PCR as a
reference, and determined a sensitivity of 97 \% and negative predictive
value of 83 \%.\textsuperscript{10} Few authors have studied the
prognostic value of chest CT. Yuan \emph{et al} . have found in a small
sample of 27 patients (of which 10 died) higher rates of consolidation
and air bronchogram in the dead patients' group.\textsuperscript{14} In
a retrospective study, Zhao \emph{et al.} found pleural effusions and
architectural distorsions to be CT signs potentially correlated with
severe deterioration in a small population of severe or deceased
patients (14/101 patients).\textsuperscript{15}

In this study, our main objective was to assess whether some chest CT
signs were associated with pejorative evolution (defined as requiring
intensive care unit hospitalization, invasive endotracheal ventilation
or a fatal outcome), for patients with COVID-19. Our secondary objective
was to evaluate the diagnostic value of chest CT versus RT-PCR.

\textbf{Patients and Methods}

\textbf{Study design}

Ethical approval of this monocentric retrospective study was delivered
by the review board of our hospital (Hospitals of Tours, Francois
Rabelais University, France). From March 19th to April 28th 2020, we
included 349 patients either suspected of COVID-19 infection or previous
RT-PCR COVID-19 positive patients to whom a chest CT scan was performed
in the radiology department.

Inclusion criteria were: clinical suspicion of COVID-19 infection with
severe symptoms requiring hospitalization or other comorbidities listed
below : patients previously hospitalized for another reason and
suspected of COVID-19 infection, patients with initial negative RT-PCR
presenting a clinical deterioration during their hospitalization.

Comorbidities were~: age \textgreater{} 65 years, chronic respiratory
disease, dialysis, cardiac insufficiency NYHA 3 or 4, history of cardiac
diseases (arterial hypertension, coronaropathy, stroke, cardiac
surgery), cirrhosis (\selectlanguage{english}[?] Child B), diabetes with complications or
requiring insulin therapy, immunosupression (chemotherapy, biotherapy,
immunosuppressive corticotherapy, uncontrolled HIV or CD4 \textless{}
200/mm\textsuperscript{3}, metastatic cancer, all types of graft), BMI
\textgreater{} 40, or pregnancy. Clinical severity scale was assessed
according to the Chinese Center of Disease Control and Prevention :
uncomplicated illness (upper respiratory tract damages, including mild
fever, cough (dry), sore throat, nasal congestion, headache, myalgia, or
malaise. Symptoms~of a more serious disease, such as dyspnoea, are not
present), moderate pneumonia with dyspnoea, severe pneumonia (Sp02
\textless{} 90 \% in ambient air, tachypnoea \textgreater{} 30/min), and
acute respiratory distress syndrome (clinical and ventilation criteria~:
mild acute respiratory distress syndrome (ARDS) = 200 mmHg \textless{}
PaO2/FiO2 \selectlanguage{english}[?] 300 mmHg (positive PEEP or CPAP \selectlanguage{english}[?] 5 mmHg if not ventilated
or non-invasive ventilation)), moderate ARDS = 100 mmHg \textless{}
PaO2/FiO2 \selectlanguage{english}[?] 200 mmHg, and severe ARDS = PaO2/FiO2 \selectlanguage{english}[?] 100
mmHg).\textsuperscript{16,17}

\textbf{RT-PCR test and clinical synthesis}

RT-PCR and chest CT were performed for these patients. Coronavirus
nucleic acid was collected with nasopharyngeal swab or/and bronchial
aspiration. RT-PCR was performed using gene amplification RdRpE, and/or
N (CNR Pasteur technic, AllPlex Seegene, Bosphore Anatolia; depending on
availabilities). For patients who presented a high clinical probability
of infection, two or three RT-PCR were performed if the previous results
were negative, with a minimum of 48-72 hours between samples.

If one RT-PCR was positive, COVID-19 diagnosis was confirmed. In case of
multiple chest CTs, we used the one that was closest, timewise, to the
first RT-PCR. All patients were included whatever the time between
RT-PCR and chest CT.

We also included the notion of highly probable COVID-19 infection, i.e.
some cases had multiple RT-PCR negative results but the clinical
(dyspnoea, fever, fatigue, cough), biological history (lymphopenia, high
reactive C-protein, high D-Dimers and LDH), chest CT and epidemiology
(contagion with a positive RT-PCR) arguments were consistent with a
COVID-19 infection.\textsuperscript{10} There was a follow-up and
additional chest CTs to conclude if the patient was infected or not,
based on clinical assessment and medical records.

\textbf{Primary outcome}

The primary outcome was pejorative evolution, a composite criterion
which comprises use of invasive endotracheal ventilation, intensive care
unit hospitalization (ICUH), or death.

\textbf{Chest CT protocol}

Images were obtained in supine position by one of the two following CT
scanners~: an Aquilion Prime 160 (Toshiba, Japan)~or a Somatom Force CT
VB10 (Siemens Healthinners, Germany). Mean scanning parameters were:
tube voltage = 120 kV, automatic dose modulation (30-210 mAs), matrix
512 x 512, pitch 0,35-0,99, slice thickness = 0,5 mm, and a field of
view = 500 mm x 500 mm. A 0,5 mm slice thickness was used after image
reconstruction. When a pulmonary embolism was suspected, iodinated
contrast media (300 mg/l) was intravenously injected (3 to 4 ml/s)
according to patient weight, with bolus tracking in the main pulmonary
artery. Images reconstructed were archived and transferred to the
informatic network (PACS).

\textbf{Chest CT images analysis}

Three radiologists (18 years thoracic radiology specialist, 10 years
general radiologist and 2 years radiologist resident) blinded to RT-PCR
results reviewed CT images and concluded either to COVID-19 infection or
not, according to the consensual signs described in COVID-19 chest
damages\textsuperscript{7}. Clinical history was available for
interpretation.

Chest CT signs were analysed according to the Fleishner Society
glossary\textsuperscript{18} : ground glass-opacities (patchy, nodular
or mixed), crazy paving (thickened intralobular and interlobular lines
in a ground glass opacity), subpleural curvilinear bands, consolidation
areas, air bubble sign, vascular dilatation, bronchial distortion,
reticular interlobular thickening, pleural effusion, pleural thickening,
number of involved lobes, inferior predominance, laterality, lung
localisation (subpleural, central or dual distribution), compatible CT
aspect of ARDS) compatible CT aspect of organized pneumonia, compatible
CT aspect of cardiac failure, lymphadenopathy, emphysematous lesions,
bronchial thickening, endobronchial secretion, centrilobular nodule, and
total lung volume involvement (0\%, \textless{} 10\%, 10-25\%, 25-50\%,
50-75\%, \textgreater{} 75 \%).

Compatible CT aspect of organized pneumonia included consolidation
(nodular, linear, perilobular, or peribronchovascular), subpleural
curvilinear bands, halo sign, and/or atoll
sign.\textsuperscript{19}Bronchial distortion is defined as bronchial
dilatation, with irregular contours, focalized in the areas affected by
the ground glass opacities, consolidation, or crazy
paving.\textsuperscript{20}

\textbf{Statistical Analysis}

Statistical analysis was performed with Matlab(r) R2007b (MathWorks Inc.,
Natick, USA). Qualitative variables were reported with number,
percentage and quantitative variables with mean and standard deviation.

We calculated sensitivity, specificity, positive predictive value (PPV),
negative predictive value (NPV) and their respective 95 \% confidence
interval for the diagnosis of a COVID-19 infection with chest CT versus
RT-PCR (reference).

The associations between the mortality or morbidity (invasive
endotracheal ventilation or ICUH) and chest CT signs of COVID-19
infection (ground glass opacities, crazy paving, consolidation area,
subpleural curvilinear bands, bronchial distortion, vascular dilatation,
air bubble sign, interlobular thickening, total volume {[}50-100 \%
versus \textless{} 50\%{]}, compatible aspect of organized pneumonia,
compatible CT aspect of ARDS, distribution {[}subpleural, central, and
dual i.e. central and subpleural{]}, inferior localization, number of
involved lobes (0 to 3 VS 4 or 5 involved lobes) were evaluated using
Chi2 tests when applicable (all theorical numbers superior to 5), and
Fisher's exact test otherwise.

All test results with a p-value \textless{} 0.05 were considered
statistically significant.

\textbf{Results}

\textbf{Clinical and population characteristics}

We included 349 patients suspected of COVID-19 who underwent chest CT.
Their clinical and demographic characteristics are resumed in Table 1.
There were 136 patients with compatible CT signs of COVID-19 infection
and 109 were RT-PCR positive (Figure. 1). The two positive and negative
RT-PCR groups were comparable in term of age, sex and comorbidity rate.
73 of 109 patients (67 \%) with positive RT-PCR had severe symptoms
(severe pneumonia or ARDS as described above), presenting high rates of
ICUH (35,7 \%), invasive endotracheal ventilation (25,7 \%) and death
(10,1 \%). Mean time interval between chest CT and RT-PCR was inferior
to 1,5 days. Patients generally had chest CT the same day or the day
after hospitalization and 6,2 days mean time after the first symptoms.
Table 2 presents the chest CT signs of the 109 COVID-19 patients who had
positive RT-PCR.

There were 34 patients with compatible COVID-19 CT, i.e. patients with
negative RT-PCR but compatible chest CT. Despite repeated RT-PCR tests,
14 were considered as probable COVID-19 infection by physicians at the
end of hospitalization, based on clinical assessment. 6,4 \% of RT-PCR
positive patients did not show COVID-19 CT signs (normal CT or not
compatible CT signs). Typical chest CT signs in the 109 positive RT-PCR
COVID-19 patients are described according to the delay between first
symptoms and the first CT (Days 0 to 6, 7 to 14, and \textgreater{} 14)
in Figure. 2. Maximum peak of CT signs was during the second week after
the beginning of symptoms, in relatively similar proportions.

\textbf{CT signs and pejorative evolution}

Associations between COVID-19 typical CT signs and intensive care unit
hospitalization, use of invasive endotracheal ventilation and death are
summarized in Table 3, with the calculated p-values, only for the 109
RT-PCR positive patients.

Bronchial distortion was significatively associated with mortality (p =
0,018), ICUH and invasive endotracheal ventilation (p \textless{}
10\textsuperscript{-3}). Vascular dilatation and a number of involved
lobes \selectlanguage{english}[?] 4 were significatively associated with invasive endotracheal
ventilation and ICU hospitalization (p \textless{}
10\textsuperscript{-3}). Total lung volume involvement \selectlanguage{english}[?] 50 \% was also
significatively associated with death, invasive endotracheal ventilation
and ICUH (p \textless{} 10\textsuperscript{-3}). Air bubble sign (p =
0,039), interlobular (p = 0,026) and peribronchovascular thickening (p =
6.10\textsuperscript{-3}) were associated with invasive endotracheal
ventilation.

\textbf{Chest CT diagnostic value}

With RT-PCR as the reference for the 349 patients included, sensitivity
was 93,6 \% {[}95\% CI 89-98,2{]}, specificity was 85,8 \%
{[}81,4-90,2{]}, PPV was 75 \% {[}67,7-82,3{]}, NPV was 96,7 \%
{[}94,3-99,1{]}, with a prevalence of 31,2 \%.

\textbf{Discussion}

Among positive RT-PCR COVID-19 patients, bronchial distortion and total
lung involvement volume \selectlanguage{english}[?] 50 \%,~are the only~signs~associated with a
fatal outcome, as shown in Figures 3a, 3b and 4. We also found that
vascular dilatation, bronchial distortion, lesional expansion (total
lung involvement \selectlanguage{english}[?] 50 \% or \selectlanguage{english}[?] 4 damaged lobes) are significantly
associated with invasive endotracheal ventilation or ICUH. Maybe some of
these signs are not correlated with~death due to our sample size.
Vascular dilatation, as shown in Figures 3b and 4, could be due to
endothelial lesion with inflammatory vasodilatation or maybe to
parenchymal retraction associated with fibrosis. The air bubble sign is
more frequent in invasive endotracheal ventilation, it could correspond
to a bronchioloalveolar dilatation linked with fibrosing damages or a
previous existing cyst revealed by the diffuse infection. The
significantly higher frequency of interlobular and peribronchovascular
thickening in the invasive endotracheal ventilation group could be due
to interstitial oedema observed in~congestive heart failure~(6/109
patients) and are not specific of COVID-19 infection. However, contrary
to Zhao~\emph{et al.} , lymphadenopathy and pleural effusion~were~not
associated with a pejorative evolution in our
cohort.\textsuperscript{12}

We also have observed a compatible pattern with organized pneumonia (OP)
in more than 50 \% of patients : an example is shown in Figure 3c.
Association between OP and fibrosis lesions has been observed in a
pulmonary autopsy of one COVID-19 patient as a histologic pattern of
acute fibrinous and organizing pneumonia, by Copin~\emph{et al.} ,
consistent with the CT aspect.\textsuperscript{25}

Frequency and type of chest CT signs are similar to other previous
studies except for consolidation and bronchial distortion, more
prevalent in our study probably due to the clinical severity of our
patients.\textsuperscript{13,20--23} In a previous metanalysis,
Salehi~\emph{et al.} ~have described 80 \% of air bronchograms in
COVID-19 lung damages.\textsuperscript{24} Rather than air bronchograms,
it seems more pertinent to use bronchial distortion as a typical sign of
secondary fibrosing damage observed in severe COVID-19 pneumoniae.

All the CT signs must be analysed independently from each other: indeed,
if the presence of ground glass opacities (frequent sign whatever
clinical presentation) was~not a pejorative evolution predictive sign,
its expansion over 50 \% of volume the lung~was~predictive of a
pejorative evolution as shown in this study.\textsuperscript{20,24,26}

We have~found~that chest CT has a strong diagnostic value in COVID-19
infection comparing to RT-PCR, with a sensibility of 93,6 \%,
specificity of 85,8 \%, PPV of 75 \% and NPV of 96,7 \%, as described in
previous studies. Our sensibility was concordant with other studies,
e.g. 97 \% in Ai~\emph{et al.} \textsuperscript{10,29} However, our
specificity and PPV are better, perhaps due to the recruitment of our
patients in terms of clinical severity.

Figure 2 shows that the proportion of different CT signs increases
during the second week and decreases after, so it~confirms that
pulmonary~extension is maximal around the
10\textsuperscript{th}~day.\textsuperscript{27}~Furthermore, we noted
that all the typical~COVID-19 CT~signs~were~present~during the~first
week in similar~proportions. Contrary to Pan~\emph{et al.} , we haven't
observed a relative predominance of ground glass opacities in the first
week or consolidation predominance in the second week (perhaps due the
exclusion of severe patients in these
studies).\textsuperscript{28}Indeed, several kinds of CT patterns seem
to exist in~COVID-19 pneumonia,~rather than a unique stereotyped
chronological evolution, depending on the type and degree of
histological damage.

This study has some limitations. It is a retrospective study. Only one
CT scan was included per patient. No CT aspect evolution analysis was
performed; however, the rapidity of symptoms evolution could be another
predictive factor of pejorative evolution. Other futures studies should
consider this point. It is possible that some signs are not associated
with pejorative evolution because of a relatively small~number of
deaths.

\textbf{Conclusion}

Chest CT is a fast tool, with immediate results,~which~seems to have an
excellent diagnostic value.~CT also allows complication detection,
differential diagnosis exclusion~and seems to help assess the prognosis
as described previously and in this study. This exam should
be~readily~proposed for COVID-19 patients according to clinical
criterias and local availabilities.

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18. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J.
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19. Zare Mehrjardi M, Kahkouee S, Pourabdollah M. Radio-pathological
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21. Liu K-C, Xu P, Lv W-F, et al. CT manifestations of coronavirus
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22. Guan CS, Lv ZB, Yan S, et al. Imaging Features of Coronavirus
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29. Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for Typical
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Testing.\emph{Radiology} . Published online February 12, 2020:200343.
doi:10.1148/radiol.2020200343\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Variable} & \textbf{Values} & \textbf{Values}\tabularnewline
\midrule
\endhead
& RT- PCR COVID + (109 patients) & RT-PCR COVID -- (240
patients)\tabularnewline
Age & 64,6 (17,2) & 64,5 (18,9)\tabularnewline
Male sex & 61 (55,6 \%) & 129 (53,9 \%)\tabularnewline
Comorbidity & 81 (74 \%) & 180 (75,3 \%)\tabularnewline
Clinical severity & &\tabularnewline
No & 12 (11 \%) & 123 (51,5 \%)\tabularnewline
Mild & 24 (22 \%) & 64 (26,8 \%)\tabularnewline
Severe & 46 (42,2 \%) & 49 (20,5 \%)\tabularnewline
Mild ARDS & 1 (0,9 \%) & 0 (0 \%)\tabularnewline
Moderate ARDS & 15 (13,7 \%) & 3 (1,2 \%)\tabularnewline
Severe ARDS & 11 (10,1 \%) & 0 (0 \%)\tabularnewline
ICUH & 39 (35,7 \%) & 12 (5 \%)\tabularnewline
Invasive endotracheal ventilation & 28 (25,7 \%) & 6 (2,5
\%)\tabularnewline
Death & 11 (10,1 \%) & 7 (2,9 \%)\tabularnewline
Life status unknown at the end of the study & 11 (10,1 \%) & 0
(0\%)\tabularnewline
Number of unknown RT-PCR before CT & 55 (50,5 \%) & 158 (68
\%)\tabularnewline
Average time between first symptom and CT (days) & 6,2 \selectlanguage{ngerman}± 5,1 & 6,2 \selectlanguage{ngerman}±
4,9\tabularnewline
Average time between first symptom and CT among patients in ICUH (days)
& 5,9 \selectlanguage{ngerman}± 4,3 & 7,4 \selectlanguage{ngerman}± 8,6\tabularnewline
Average time between CT and RT-PCR (days) & 1,42 \selectlanguage{ngerman}± 2 & 1,41 \selectlanguage{ngerman}±
2,9\tabularnewline
Average time between RT-PCR and CT if RT-PCR results are not known
(days) & 1,49 \selectlanguage{ngerman}± 2,48 & 1,32 \selectlanguage{ngerman}± 2,1\tabularnewline
Average time between RT-PCR and CT if RT-PCR results are known (days) &
2,11 \selectlanguage{ngerman}± 2,38 & 1,37 \selectlanguage{ngerman}± 2\tabularnewline
Average time between admission and CT (days) & 1,1 \selectlanguage{ngerman}± 2,15 & 1,1 \selectlanguage{ngerman}±
2\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{Table 1 -} Clinical and demographic characteristics of the 349
patients included -- Qualitative values are indicated as number and
percentages. Quantitative values are indicated as mean and standard
deviation. ARDS, Acute Respiratory Distress Syndrom; CT = Computed
Tomography; ICUH, Intensive Care Unit Hospitalization; RT-PCR, Real Time
Reverse-Transcription Polymerase Chain Reaction.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Signs}\strut
\end{minipage} & \begin{minipage}[b]{0.47\columnwidth}\raggedright\strut
\textbf{Values}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Ground glass opacities\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
98 (89,9 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Crazy paving\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
65 (59,6 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Not systematized consolidation area\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
39 (35,8 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Subpleural curvilinear bands\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
63 (57,8 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Bronchial distortion\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
45 (41,3 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Vascular dilatation\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
25 (22,9 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Air bubble Sign\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
12 (11 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Interlobular thickening\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
14 (12,8 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Compatible aspect of ARDS\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
7 (6,4 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Compatible aspect of organized pneumonia\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
59 (54,1 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Compatible aspect of cardiac additional decompensation\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
6 (5,5 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Lymphadenopathy\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
13 (11,9 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Bronchial thickening\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
13 (11,9 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Endobronchial secretion\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
7 (6,4 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Centrilobular nodule\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
7 (6,4 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pneumothorax\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
2 (1,8 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pulmonar embolism\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
6 (5,5 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Emphysematous lesions\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
5 (4,6 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Systematized consolidation\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
6 (5,5 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pleural effusion\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
17 (15,6 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Pleural thickening\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
4 (3,7 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Bilateral\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
102 (9,3 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Unilateral\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
3 (2,7 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Subpleural localization\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
104 (95,4 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Central localization\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
48 (44 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Dual distribution\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
52 (47,7 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Inferior localization\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
75 (68,8 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
Number of involved lobes\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
4,2 (1,4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
Volume (total lung involvement)\strut
\end{minipage} & \begin{minipage}[t]{0.48\columnwidth}\raggedright\strut
0\% : 5 (4.6\%) \textless{} 10\% : 13 (11.9\%) 10-25 \% : 24 (22 \%) 25
-50 \% : 31 (28,4 \%) 50 -- 75 \% : (14,7 \%) \textgreater{}75 \% :
(18,4 \%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
No CT signs\strut
\end{minipage} & \begin{minipage}[t]{0.47\columnwidth}\raggedright\strut
4 (3,7 \%)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2 -} First chest CT signs found for the 109 positive
COVID-19 All signs are described with number and percentage, except the
number of involved lobes which is described with mean and standard
deviation. ARDS, Acute Respiratory Distress Syndrom; CT, Computed
Tomography.\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& ICUH & Invasive endotracheal ventilation & Death\tabularnewline
\midrule
\endhead
& p-value & p-value & p-value\tabularnewline
Ground glass opacities & - & - & -\tabularnewline
Crazy paving & - & - & -\tabularnewline
Not systematized consolidation area & - & - & -\tabularnewline
Subpleural curvilinear bands & - & - & -\tabularnewline
Bronchial distortion & \textless{} 10\textsuperscript{-3} & \textless{}
10\textsuperscript{-3} & 0,018\tabularnewline
Vascular dilatation & \textless{} 10\textsuperscript{-3} & \textless{}
10\textsuperscript{-3} & -\tabularnewline
Air bubble sign & - & 0,039 & -\tabularnewline
Interlobular thickening & - & 0,026 & -\tabularnewline
Compatible aspect of ARDS & \textless{} 10\textsuperscript{-3} &
\textless{} 10\textsuperscript{-3} & -\tabularnewline
Subpleural localization & - & - & -\tabularnewline
Central localization & 0,019 & - & -\tabularnewline
Dual distribution & 0,010 & - & -\tabularnewline
Inferior localization & - & - & -\tabularnewline
Compatible aspect of organized pneumonia & - & - & -\tabularnewline
Peribronchovascular thickening & - & 6.10\textsuperscript{-3} &
-\tabularnewline
Number of involved lobes {[}[?]3 VS [?]4{]} & 3,8.10\textsuperscript{-3} &
4,25.10\textsuperscript{-3} & -\tabularnewline
Total lung volume involvement & & &\tabularnewline
\textless{}50 VS [?] 50 \% & \textless{} 10\textsuperscript{-3} &
\textless{} 10\textsuperscript{-3} & \textless{}
10\textsuperscript{-3}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3 -} Association between CT chest signs and intensive care
unit hospitalization, invasive endotracheal ventilation and death among
positive RT-PCR COVID-19 patients. Dashes correspond to p \textgreater{}
0,05. ARDS, Acute Respiratory Distress Syndrom; CT, Computed Tomography;
ICUH, Intensive Care Unit Hospitalization.

\textbf{Figure 1.} Flow-chart of the 349 patients suspected of COVID-19
infection included in the study.

\textbf{Figure 2.} Main chest CT signs in the 109 COVID-19 positive
RT-PCR cases according to the delay between first symptoms and the first
chest CT. CT, Computed Tomography; RT-PCR, Real Time
Reverse-Transcription Polymerase Chain Reaction.

\textbf{Figure 3.} Chest CT in positive RT-PCR COVID-19 cases - (a) A 74
years old man in ICU with endotracheal ventilation, 11 days after first
symptoms, massive bronchial distortion (white arrow) in all the right
lung, large areas of ground glass opacities and subpleural
consolidation, with [?] 75 \% of total lung involvement. Note a left
anterior loculated pneumothorax and a left posterior pleural effusion
drain. (b) A 57 years old man in ICU, 13 days after first symptoms, dual
distribution areas (subpleural and central) of ground glass opacities in
the lingula and the right inferior lobe with bronchial distortion (black
arrow) and vascular dilatation (white arrow), with 50-75 \% of total
lung involvement. (c) A 67 years old man in ICU, 10 days after first
symptoms, CT aspect of organized pneumonia (white arrow) with bilateral
posterior subpleural curvilinear bands. CT, Computed Tomography; ICU,
Intensive Care Unit; RT-PCR, Real Time Reverse-Transcription Polymerase
Chain Reaction.

\textbf{Figure 4.} Chest CT of a 76 years old man in ICU, showed 10 days
after first symptoms, bilateral, large and patchy ground glass opacities
with crazy paving (white underlined dark arrow), bronchial distortion
(white arrow) and vascular dilatation (dark arrow), with 50-75 \% of
total lung involvement. CT, Computed Tomography; ICU, Intensive Care
Unit.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

