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CT imaging of pulmonary embolism in patients with COVID-19 pneumonia: a retrospective analysis

September 2020
European Radiology

September 2020

DOI:10.1007/s00330-020-07300-y

Authors:

Juanjo Rodriguez-Sevilla

Consorci MAR Parc de Salut de Barcelona

Show all 16 authorsHide

Objectives: To describe imaging and laboratory findings of confirmed PE diagnosed in COVID-19 patients and to evaluate the characteristics of COVID-19 patients with clinical PE suspicion. Characteristics of patients with COVID-19 and PE suspicion who required admission to the intensive care unit (ICU) were also analysed. Methods: A retrospective study from March 18, 2020, until April 11, 2020. Inclusion criteria were patients with suspected PE and positive real-time reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Exclusion criteria were negative or inconclusive RT-PCR and other chest CT indications. CTPA features were evaluated and severity scores, presence, and localisation of PE were reported. D-dimer and IL-6 determinations, ICU admission, and previous antithrombotic treatment were registered. Results: Forty-seven PE suspicions with confirmed COVID-19 underwent CTPA. Sixteen patients were diagnosed with PE with a predominant segmental distribution. Statistically significant differences were found in the highest D-dimer determination in patients with PE and ICU admission regarding elevated IL-6 values. Conclusion: PE in COVID-19 patients in our series might predominantly affect segmental arteries and the right lung. Results suggest that the higher the D-dimer concentration, the greater the likelihood of PE. Both assumptions should be assessed in future studies with a larger sample size. Key points: • On CT pulmonary angiography, pulmonary embolism in COVID-19 patients seems to be predominantly distributed in segmental arteries of the right lung, an assumption that needs to be approached in future research. • Only the highest intraindividual determination of d-dimer from admission to CT scan seems to differentiate patients with pulmonary embolism from patients with a negative CTPA. However, interindividual variability calls for future studies to establish cut-off values in COVID-19 patients. • Further studies with larger sample sizes are needed to determine whether the presence of PE could increase the risk of intensive care unit (ICU) admission in COVID-19 patients.

Segmental left lower lobe PE over a severe lung involvement. CTPA, with lung window (a, b, c) and volume rendering (d) images, shows extensive lung involvement (score 4) with typical findings as reverse halo sign (a, arrow), bilateral peripheral GGO and consolidations with perilobular distribution (b, arrows), and

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CHEST

CT imaging of pulmonary embolism in patients with COVID-19

pneumonia: a retrospective analysis

Irene Espallargas

1,2

&Juan José Rodríguez Sevilla

&Diego Agustín Rodríguez Chiaradía

4,5,6,7

&Antonio Salar

3,5

Guillem Casamayor

&Judit Villar-Garcia

9,5

&Anna Rodó-Pin

4,5,6,7

&Salvatore Marsico

&Santiago Carbullanca

Diego Ramal

&Luis Alexander del Carpio

&Ángel Gayete

&José María Maiques

&Flavio Zuccarino

1,10

Received: 24 April 2020 /Revised: 8 September 2020 /Accepted: 15 September 2020

#European Society of Radiology 2020

Abstract

Objectives To describe imaging and laboratory findings of confirmed PE diagnosed in COVID-19 patients and to evaluate the

characteristics of COVID-19 patients with clinical PE suspicion. Characteristics of patients with COVID-19 and PE suspicion

who required admission to the intensive care unit (ICU) were also analysed.

Methods A retrospective study from March 18, 2020, until April 11, 2020. Inclusion criteria were patients with suspected PE and

positive real-time reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Exclusion criteria were negative

or inconclusive RT-PCR and other chest CT indications. CTPA features were evaluated and severity scores, presence, and

localisation of PE were reported. D-dimer and IL-6 determinations, ICU admission, and previous antithrombotic treatment were

registered.

Results Forty-seven PE suspicions with confirmed COVID-19 underwent CTPA. Sixteen patients were diagnosed with PE with

a predominant segmental distribution. Statistically significant differences were found in the highest D-dimer determination in

patients with PE and ICU admission regarding elevated IL-6 values.

Conclusion PE in COVID-19 patients in our series might predominantly affect segmental arteries and the right lung. Results

suggest that the higher the D-dimer concentration, the greater the likelihood of PE. Both assumptions should be assessed in future

studies with a larger sample size.

Key Points

•On CT pulmonary angiography, pulmonary embolism in COVID-19 patients seems to be predominantly distributed in seg-

mental arteries of the right lung, an assumption that needs to be approached in future research.

•Only the highest intraindividual determination of D-dimer from admission to CT scan seems to differentiate patients with

pulmonary embolism from patients with a negative CTPA. However, interindividual variability calls for future studies to

establish cut-off values in COVID-19 patients.

•Further studies with larger sample sizes are needed to determine whether the presence of PE could increase the risk of intensive

care unit (ICU) admission in COVID-19 patients.

*Irene Espallargas

igespallargas@gmail.com

Department of Radiology, Hospital del Mar, Passeig Maritim 23-25,

08003 Barcelona, Spain

Department of Radiology, Hospital Germans Trias i Pujol, Carretera

de Canyet S/N, 08916 Badalona, Spain

Department of Hematology, Hospital del Mar, Passeig Maritim

23-25, 08003 Barcelona, Spain

Pulmonology Department, Hospital del Mar, Passeig Maritim 23-25,

08003 Barcelona, Spain

Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Dr.

Aiguader, 88, 08003 Barcelona, Spain

Universitat Pompeu Fabra (UPF), Dr. Aiguader, 80,

08003 Barcelona, Spain

CIBERES, (ISCIII), Calle de Melchor Fernández Almagro, 3,

28029 Madrid, Spain

Department of Emergency Medicine, Hospital Germans Trias i Pujol,

Carretera de Canyet S/N, 08916 Badalona, Spain

Department of Infectious Diseases, Hospital del Mar, Passeig

Maritim 23-25, 08003 Barcelona, Spain

Department of Radiology, Hospital Sant Joan de Déu, Passeig de

Sant Joan de Déu, 2, 08950 Esplugues de Llobregat,

Barcelona, Spain

European Radiology

https://doi.org/10.1007/s00330-020-07300-y

Keywords Computed tomography angiography .Pulmonary embolism .COVID-19 .Fibrin fragment D .Intensive care units

Abbreviations

COVID-19 Coronavirus infectious disease 2019

RT-PCR Reverse-transcription polymerase

chain reaction

CTPA CT pulmonary angiography

PE Pulmonary embolism

ICU Intensive care unit

SARS-CoV-2 Severe acute respiratory syndrome

coronavirus 2

Introduction

The COVID-19 pandemic began in Wuhan (Hubei, China) in

December 2019 and rapidly spread around the world. At the

beginning of April 2020, there were over 100,000 confirmed

cases and more than 10,000 deaths in Spain. Radiological

literature has until now focused on non-contrast computed

tomography (CT) findings to describe the probability of infec-

tion [1] due to limitations of sensitive real-time reverse-tran-

scription polymerase chain reaction (RT-PCR) results [2,3].

However, the elevation of D-dimer has been reported in pa-

tients infected with the novel coronavirus [4], which, in our

institution, has led to an increase in the number of CT pulmo-

nary angiography (CTPA) requests with suspected pulmonary

embolism (PE). D-dimers are able to rule out deep vein throm-

bosis and PE in outpatients with low or intermediate clinical

probability of PE. However, unless specific cut-off levels are

used, its usefulness in hospitalised patients with suspected

thromboembolism is less established. Based on a retrospective

study, D-dimers above 2000 μg/L were predictive of the pres-

ence of PE independently of the clinical score [5]. Besides, as

D-dimer levels increase for around 7 days during the PE event,

late evaluation may lead to underestimated determination [6].

The aim of this study is to describe the imaging and laboratory

findings of confirmed PE diagnosed in COVID-19 patients.

We have evaluated the characteristics of COVID-19 patients,

with clinical suspicion of PE,whohadhadconfirmatory

CTPA and compared them to those who had not. In addition,

we also analysed the characteristics of patients with COVID-

19 and PE suspicion who required admission to the intensive

care unit (ICU).

Materials and methods

The study was approved by the Clinical Research Ethical

Committee of the Parc de Salut Mar, which due to the excep-

tionality of the pandemic emergency waived the informed

consent. A retrospective study was performed to analyse CT

scans and laboratory of COVID-19 patients admitted to our

hospital.

Clinical evaluation

Nine hundred and nineteen patients (804 laboratory-

confirmed SARS-CoV-2 and 115 pending result) with clinical

COVID-19 were hospitalised in our institution during the time

that this study data was registered. Due to sensitivity limita-

tions of RT-PCR (around 70% inthe diagnostic kit used in our

hospital), a situation already described [2,3], and delays in

obtaining results, clinical assessment was essential in the ini-

tial diagnosis of COVID-19 pneumonia (sudden onset of dry

cough, fever, or shortness of breath [4]). Inclusion criteria

were contrast-enhanced studies with CTPA protocol in adult

patients with elevated clinical suspicion of PE and both posi-

tive screening and confirmatory RT-PCR for SARS-CoV-2.

Exclusion criteria were negative or inconclusive RT-PCR,

even when clinical and imaging findings were consistent with

viral pneumonia, and other reasons for CT request other than

PE suspicion. The CT studies were searched for in the elec-

tronic database from March 18 to April 11, while the clinical

and laboratory data were collected through available electron-

ic medical records. Time from the onset of the symptoms to

the CT performance was collected under the name of time to

PE (TTP).

Severe cases of COVID-19 are associated with increased

IL-6 levels [7]. Cytokines are fundamental in managing im-

munological and severe reactions; among them, IL-6 is vital

on account of its pleiotropic impacts [8]. A recent meta-

analysis of the impact of IL-6 as disease progression predictor

was performed; presenting evidence that circulating IL-6

levels are firmly connected to the severity of COVID-19 in-

fection [9]. On the other hand, increased expression of IL-6

has correlated with an increase of the incidence of deep vein

thrombosis [10]. On behalf of this evidence, measuring IL-6

levels was considered a standard of care for COVID-19 pa-

tients in our centre, not only in the follow-up of the COVID-

19 patient status but also in the consideration of anti-

interleukin-16 agents (tocilizumab, sarilumab, siltuximab)

[10]. The first determination of IL-6 after admission was col-

lected for this study, as it would not be influenced by COVID-

19 treatments. Regarding D-dimer testing, initial values on

admission and immediately before CT were registered. The

highest D-dimer testing before the scan was also collected to

avoid underestimation due to late evaluation.

Anticoagulant therapy before the CT examination and its

doses were also registered since the intrinsic SARS-CoV-2

risk of disseminated intravascular coagulation and venous

thromboembolism has led to the recommendation of

Eur Radiol

anticoagulant treatment by expert consensus [11,12]. In our

centre, anticoagulant strategy in patients with COVID-19 has

evolved during the pandemic. In the first period, all patients

with no anticoagulation contraindications received prophylax-

is with low molecular weight heparin at standard doses rec-

ommended for medically ill patients (enoxaparin 40 mg per

day subcutaneously). In the second period, patients who had a

D-dimer above 2000 mcg/L received intermediate doses of

low molecular weight heparin (enoxaparin 1 mg/kg per day

subcutaneously), while the other patients had standard dose

prophylaxis.

Admission to the ICU for COVID-19 patients in our insti-

tution included clinical (tachypnoea, tachycardia, persistent

hypotension, Glasgow coma scale ≤14, persistent respiratory

failure under Venturi mask with 50% FIO

, and abnormal

work of breathing) and/or laboratory criteria (pH < 7.3,

HCO3 < 15 mmol/L or PaCO

> 60 mmHg, lactate

> 3.5 mmol/L, persistent renal failure, and disseminated intra-

vascular coagulation).

Imaging and interpretation

CTPA examinations were obtained in a multidetector CT

scanner (Discovery CT750 HD, GE Healthcare) by using a

dual-energy CTPA protocol (Gemstone Spectral Imaging

GSI), with the following parameters: tube voltage 80–

140 kV, 340 mA, pitch = 0.984, rotation time = 0.5 s, field

of view = 512 mm × 512 mm, 64 × 0.625-mm detector config-

uration, and slice thickness = 1.25 mm. The CT acquisition

was performed using automatic bolus-tracking technique (re-

gion of interest located at the pulmonary artery with a trigger

threshold of 150 HU) after a weight-based protocol injection

of 50–70 mL of nonionic iodinated contrast media

(Omnipaque 350, GE Healthcare) at a flow rate of 4 mL/s,

followed by a 25-mL saline flush. DICOM data was trans-

ferred to a PACS workstation (Centricity Universal Viewer

v.6.0, GE Medical Systems), for multiplanar reconstruction

and evaluation, in both lung and mediastinal windows, of

monochromatic CT angiographic images. Iodine maps were

analysed with dedicated software (GSI viewer, AW server 2.2,

GE Healthcare) and used to improve accuracy for distal per-

fusion defects [13]. Homogeneous lung perfusion did not ex-

clude the meticulous revision of pulmonary arteries on CTPA

images. Studies were considered non-diagnostic whenever

breathing or streak artefacts impaired segmental, lobar, and

main pulmonary branches evaluation. Subsegmental arteries

were carefully examined before and after iodine map inspec-

tion but a lack of complete visualisation was reported as neg-

ative CTPA. Our thoracic imaging section members (senior

radiologists with 12 and 29 years of experience) reviewed all

cases and resolved discrepancies by consensus.

PE detection and location were reported and grouped into

central and lobar PE or segmental and subsegmental PE for

analysis. The following features were used to establish the

pattern of COVlD-19 pneumonia: the presence of multiple

bilateral foci of ground-glass opacities (GGO), lower lobe

predominance with peripheral distribution that could be asso-

ciated with crazy-paving pattern, peripheral consolidation, air

bronchograms, perilobular pattern, and/or reverse “halo”sign

[14,15]. Patients were defined as positive when the pattern

was consistent with COVID-19 pneumonia and isolated as

such in wards established for this purpose.

All CT disease patterns were quantified with a score from 1

to 4 in mild (1), when there were up to 3 focal pure GGO of

less than 3 cm in maximum diameter; moderate-severe (2)

when there were more than 3 focal GGO or maximum diam-

eter superior to 3 cm; moderate-severe (3) in focal GGO

mixed with early consolidation; and severe (4) when there

were diffuse GGO or consolidation and signs of architectural

distortion [15]. As reviewed by the British Society of Thoracic

Imaging, differences between moderate and severe disease

have a great amount of subjectivity which may lead to low

interobserver agreement.

Statistical analysis

Statistical analysis was performed with the IBM SPSS

Statistics version 23.0 software (IBM). Continuous data were

expressed as median with its interquartile range and full range

and were tested for normality using the Kolmogorov-Smirnov

test. Non-normally distributed variables were compared with

the Mann-Whitney Utest. Categorical variables were de-

scribed as number (percentage) and compared with Fisher’s

exact test. Missing data implied patient exclusion for that var-

iable analysis.

Apvalue of less than 0.05 was considered statistically

significant.

Results

Forty-seven PE suspicions meeting the inclusion criteria for

COVID-19 pneumonia were registered in the Diagnostic

Imaging Department and underwent CTPA scan. None of

these studies was considered non-diagnostic. There were 17

(36%) females and 30 (64%) males, with a median age of

65 years (IQR, 54–73, range 30–94). In 45 patients (96%),

both RT-PCR and CTPA were concordant for COVID-19.

Two patients had positive RT-PCR with non-COVID-19 pul-

monary findings on the CT scan. One of these two normal CT

corresponded to a patient in “early stage”(3 days after the

onset of symptoms). The severity of the pulmonary findings

was distributed as such: 2 (4.25%) normal CT scans, two

(4.25%) mild, three (6.4%) moderate-severe, eleven (23.4%)

moderate-severe, and 29 (61.7%) severe cases (Fig. 1).

Twenty-three patients (49%) were admitted to the ICU.

Eur Radiol

Thirty-six patients (77%) received enoxaparin treatment be-

fore the CT examination: prophylactic dosage 40 mg/day (n=

18, 50%), intermediate doses mg/kg/day (n= 17, 47.2%), and

full-dose regimen mg/kg/12 h (n= 1, 2.8%). Sixteen patients

(34%) were diagnosed with PE with the clinicoradiologic

characteristics being shown in Table 1. Three patients

(18.75%) had central PE and 4 patients (25%) had lobar PE,

while 9 patients (56.25%) had purely segmental (5, 31.25%)

or subsegmental (4, 25%) PE (Figs. 2,3,4,and5). The right

lung was involved in 15 cases (93.75%) and in 9 cases

(56.25%), the left lung was affected. Three patients had CT

signs of right cardiac overload, with one of them having cen-

tral filling defects and the other twolobar orsegmental arteries

affected (Fig. 3). The median time to PE (TTP) was 16 days

Table 1 Confirmed PE in COVID-19 patients

D-dimer (μg/L) TTP (days) PE Sites of PE Anticoagulant

therapy

prior to CT

ICU

Gender Age (y) Initial Highest DDCT

Patient 1 M 62 310 4330 2330 10 Lobar + segmental RUL,RLL,LUL, LLL Prophylaxis Yes

Patient 2 F 76 1420 35,200 32,140 21 Central Bilateral Prophylaxis Yes

Patient 3 F 48 10,050 19,680 4700 12 Segmental RLL, RUL Prophylaxis Yes

Patient 4 M 73 650 33,600 20,280 14 Segmental RUL, LUL, LLL, lingula Prophylaxis Yes

Patient 5 M 78 > 35,200* > 35,200* > 35,200 2 Central Bilateral No No

Patient 6 F 34 2140 5930* 5930 17 Segmental RLL Prophylaxis Yes

Patient 7 F 69 540 5140 4360 14 Lobar + segmental LLL, LUL, RLL, RUL Intermediate Yes

Patient 8 F 72 2350 31,550 12,160 15 Central Bilateral Intermediate No

Patient 9 F 59 1320 6120 5620 12 Lobar + segmental LUL,LLL,RUL,RLL,ML Prophylaxis No

Patient 10 M 69 3510 3510 2030 20 Subsegmental RLL Prophylaxis No

Patient 11 M 56 350 35,200 9900 29 Subsegmental RUL Intermediate Yes

Patient 12 M 59 360 15710* 15,710 17 Subsegmental LLL Intermediate Yes

Patient 13 M 48 1070 12,950 3790 18 Subsegmental RUL Intermediate Ye s

Patient 14 F 94 6570* 6570* 6570 3 Segmental ML, RUL, LLL No No

Patient 15 M 71 390 35,200 4670 25 Segmental RUL Intermediate Yes

Patient 16 M 58 2100 23,970 10,840 22 Lobar RLL Intermediate Yes

DDCT,D-dimer prior to the CT. y,year;M,male;F,female;TTP,timeToPE;PE, acute pulmonary embolism; ICU, intensive care unit; RLL, right lower

lobe; RUL, right upper lobe; ML, median lobe; LUL, left upper lobe; LLL, left lower lobe. Sites of PE in italics are the lobar affected arteries. *D-dimer

values are the same from the DDCT

Fig. 1 Images ordered by score

from the upper left to bottom right

in mild (a= score 1), moderate-

severe (b= score 2), moderate-

severe (c= score 3), and severe

(d= score 4)

Eur Radiol

(IQR 12–20.75, range 2–29). The patient with the lowest TTP

(2 days) had been discharged from a pacemaker insertion

2 days before the onset of symptoms.

In COVID-19 patients with PE, the highest intraindividual

D-dimer values were statistically significant when compared

with the non-PE group (p= 0.015). No other differences

between groups regarding gender, age, the rest of D-dimer

determinations, lung disease score, initial IL-6, anticoagulant

therapy, or anticoagulant doses prior to the CT were statisti-

cally significant. However, a difference in the means of initial

IL-6 in PE patients (125.08 pg/mL) versus non-PE patients

(534.82 pg/mL) was seen. There were no differences in the

Fig. 2 Segmental left lower lobe PE over a severe lung involvement.

CTPA, with lung window (a,b,c) and volume rendering (d)images,

shows extensive lung involvement (score 4) with typical findings as

reverse halo sign (a, arrow), bilateral peripheral GGO and

consolidations with perilobular distribution (b,arrows),and

architectural distortion with peripheral sparing (c, arrows). We can also

appreciate (e) a small peripheral thrombus (arrow) in a segmental artery of

the left lower lobe. Sagittal iodine map image (f) allows us to define

segmental vessel obstruction (arrow) and peripheral hypoperfusion

(asterisk)

Fig. 3 Segmental left lower lobe and right upper lobe PE. Segmental

bilateral embolisms (arrows) can be appreciated in axial (a,b) and oblique

MIP and VR images (e,f) over a moderate-severe (score 3) pulmonary

involvement (d). Signs of right cardiac overload (black arrow) with in-

terventricular septum shifting towards the left ventricle are shown in c

Eur Radiol

sites of PE with respect to either D-dimer determinations or

previous antithrombotic treatment.

Even though 11/16 patients (68.8%) with PE were admitted

to the ICU compared with 12/31 (38.7%) in the negative

CTPA group, there were no statistically significant differences

in the 2-sided Fisher’s exact test (p= 0.069) regarding ICU

admission. On analysing the ICU admission data in suspected

PE patients, statistically significant differences were seen in

anticoagulant therapy prior to CT (p= 0.036), as patients in

the ICU were more likely to receive antithrombotic treatment

and also higher dosages (p= 0.007). Significant differences

were also seen in initial IL-6 (p< 0.001), being higher in ad-

mitted ICU patients (mean 565.8 pg/mL versus 236.61 pg/mL

in non-ICU admitted patients). Differences were found re-

garding the highest D-dimer determinations (15,195.22 μg/L

in ICU admitted patients vs 9541.3 μg/L in non-ICU admitted

patients), although they were not statistically significant (p=

0.084). There were no statistically significant differences re-

garding lung disease score; however, a slightly higher score

was seen in ICU-admitted patients (mean 3.13 in non-ICU

patients versus 3.57 in ICU patients).

Discussion

CT findings in COVID-19 patients were very similar to the

ones described in other countries, with predominantly periph-

eral ground-glass foci that evolved into consolidation and ar-

chitectural distortion [3,14,16]. Lung disease scores were

significantly high, which correlates with severe illness in pa-

tients with PE suspicion. There was an equal number of uni-

lateral and bilateral PE, emphasising a majority of segmental

PE (Table 1). The predominant involvement of the right lung,

especially its upper lobe, is also interesting, while the median

lobe and the lingula seem to have rarely been affected.

COVID-19 patients have difficulties holding their breath

during CTPA acquisition, which diminishes their eligibility

for peripheral PE. Dual-energy CTPA protocol may help to

Fig. 4 Saddle pulmonary embolism. Saddle pulmonary embolism can be appreciated in axial (b) mediastinal window, over a moderate-severe (score 3)

pulmonary involvement (c). Iodine map image depicts a hypoperfusion area (a; asterisk) in the right lung

Fig. 5 Bilateral PE with segmental left lower lobe pulmonary infarct over

a severe lung involvement. CTPA (a,b,c) shows bilateral thrombi

(arrows), one located in the distal portion of a segmental artery of the

left lower lobe (c). Pulmonary window image (d) depicts multiple GGO

areas and consolidations, with typical peripheral sparing consistent with

COVID-19 lung involvement. Iodine map images (eand f) allow us to

define right lung hypoperfusion (e; asterisk) and a triangular

hypoperfused lesion (f; asterisk), inside the extensive lung involvement

and distal to the arterial thrombus, representing a pulmonary infarct

Eur Radiol

detect distal involvement by depicting hypoperfused areas in

the iodine maps (Figs. 2,4,and5). However, in this series, we

did not monitor the number of cases diagnosed only by

DECT, as both CTPA and DECT were used to establish PE

diagnosis. Even though no studies were considered “non-di-

agnostic”, some subsegmental defects may have remained un-

detected due to respiratory motion artefacts. A recent study by

Idilman et al [17] also suggested that DECT analysis might

depict perfusion deficits in mild COVID-19 patients that

would otherwise be missed with conventional CT angiogra-

phy. Additional imaging testing, such as perfusion SPECT/CT

or DVT ultrasound as a thrombosis screening test, could also

be implemented in these patients [10] to increase the certainty

of PE and to complement clinical evaluation. It is also impor-

tant to draw attention to the fact that several patients (n=18),

even though they had COVID-19-compatible CT findings,

were excluded from this study because the RT-PCR results

were negative or inconclusive. The low sensitivity of RT-PCR

has been an added obstacle for identifying COVID-19

patients.

Nevertheless, given the results, there are some highlights to

underline: the presence of PE may seem to increase the risk of

ICU admission in COVID-19 patients, despite some limita-

tions that will be addressed later. Differences observed in the

highest D-dimer values could imply that sequential D-dimer

testing could improve the early diagnosis of PE in these pa-

tients. Since D-dimer elevation is a common finding among

COVID-19 patients [4], further studies are needed to establish

a detection cut-off value. This would avoid unnecessary radi-

ation and infection risk to healthy individuals during

intrahospital patient transport [18]. This study could also raise

an initial recommendation referring to necessary IL-6 testing

at hospital admission for acute monitoring of patients with

higher determinations, as it could indicate worse clinical evo-

lution, while on its own it does not seem to correlate with PE

probability.

There were no significant differences in the probability of

PE between anticoagulated patients and those receiving no

treatment before CT. No significant differences either were

found regardless of the anticoagulation doses received.

However, due to the limited sample, the absence of differ-

ences between central or lobar PE and segmental or

subsegmental PE regarding anticoagulant dosage is difficult

to evaluate and could be a starting point for upcoming studies.

Further investigation about antithrombotic prophylaxis with a

larger sample is also required to assess risk benefit and opti-

mumdosages.AsstatedbyTangetal[11], the selection of

patients to receive anticoagulant treatment should be selective

and supported by evidence, and the need to establish a cut-off

value for the change in anticoagulant regimen is primarily

required. Attention and follow-up of these patients should be

taken into account as haemorrhagic events have been de-

scribed among COVID-19 patients [19].

It is important to remark on the limitations of the

presented results. First, the sample size of examination

is moderately scarce; therefore, it is intended to raise

the alarm about thrombotic events in a COVID-19 sce-

nario and provide a source for future studies with larger

samples. The retrospective nature of the study could

only show an association but not determine correlation:

it is unclear whether PE is a result of severe presenta-

tion of COVID-19, as disease extent (score) was similar

in both PE and non-PE groups. IL-6 determination on

admission as a biomarker of proinflammatory state was

not significantly different between these groups. These

results suggest that PE may be unrelated to the severity

of COVID-19. Gervaise et al [20] also found no differ-

ences in the severity of pulmonary findings in CT and

suggest the association between APE and non-severe

and non-hospitalised COVID-19 patients. However, PE

presence alone seems to increase the chance of ICU

admission (68.8% vs 38.7% in the negative CTPA

group), which should be confirmed with prospective

studies with larger sample sizes. However, due to the

design of this study, it is not possible to establish

whether PE was present before or after ICU admission.

Other risk factors for PE such as body mass index,

recent surgery, comorbidities, or subjacent malignant

disease were not controlled and could induce bias.

The highest frequency of involvement of the right lung

is possibly representative of a larger COVID-19 popula-

tion despite the small sample, as blood flow distribution

in the supine and prone positions is higher to the right

lung [21]. On the other hand, the upper segmental pre-

dominance could be the result of the sample size. Despite

these limitations, the patients recruited for this study were

exclusively confirmed COVID-19 patients with clinical

suspicion of PE. These restrictive inclusion criteria lead

to a more homogeneous sample that was thoroughly ex-

amined and provided important outcomes for future

studies.

Conclusion

PE in COVID-19 patients is a problematic issue that, in

our series, predominantly seems to affect segmental arter-

ies and the right lung, especially its upper lobe. However,

this statement is based in a small sample of individuals

and therefore needs to be approached in future research.

The results also suggest that the higher the D-dimer con-

centration, the greater the likelihood of PE, an assumption

that might be assessed in future studies with a larger sam-

ple size. Moreover, PE could increase the probability of

ICU admission even though it might not be linked with

the severity of COVID-19 pneumonia.

Eur Radiol

Funding The authors state that this work has not received any funding.

Compliance with ethical standards

Guarantor The scientific guarantor of this publication is Flavio

Zuccarino.

Conflict of interest The authors of this manuscript declare no relation-

ships with any companies whose products or services may be related to

the subject matter of the article.

Statistics and biometry Guillem Casamayor kindly provided statistical

advice for this manuscript.

No complex statistical methods were necessary for this paper.

Informed consent Written informed consent was waived by the

Institutional Review Board.

Ethical approval Institutional Review Board approval was obtained.

Methodology

•retrospective

•cross sectional study

•performed at one institution

References

1. Prokop M, van Everdingen W, van Rees Vellinga T et al (2020)

CO-RADS - a categorical CT assessment scheme for patients with

suspected COVID-19: definition and evaluation. Radiology. https://

doi.org/10.1148/radiol.2020201473:201473

2. Xie X, Zhong Z, Zhao W, Zheng C,Wang F, Liu J (2020) Chest CT

for typical 2019-nCoV pneumonia: relationship to negative RT-

PCR testing. Radiology. https://doi.org/10.1148/radiol.

2020200343

3. Ai T, Yang Z, Hou H et al (2020) Correlation of chest CT and RT-

PCR testing in coronavirus disease 2019 (COVID-19) in China: a

report of 1014 cases. Radiology. https://doi.org/10.1148/radiol.

2020200642

4. Huang C, Wang Y, Li X et al (2020) Clinical features of patients

infected with 2019 novel coronavirus in Wuhan, China. Lancet

395:497–506

5. Bosson JL, Barro C, Satger B, Carpentier PH, Polack B, Pernod G

(2005) Quantitative high D-dimer value is predictive of pulmonary

embolism occurrence independently of clinical score in a well-

defined low risk factor population. J Thromb Haemost 3:93–99

6. Crawford F, Andras A, Welch K, Sheares K, Keeling D, Chappell

FM (2016) D-dimer test for excluding the diagnosis of pulmonary

embolism. Cochrane Database Syst Rev. https://doi.org/10.1002/

14651858.CD010864.pub2

7. Gong J, Dong H, Xia SQ et al (2020) Correlation analysis between

disease severity and inflammation-related parameters in patients

with COVID-19 pneumonia. medRxiv. https://doi.org/10.1101/

2020.02.25.20025643

8. Chen X, Zhao B, Qu Y etal (2020) Detectable serum SARS-CoV-2

viral load (RNAaemia) is closely correlated with drastically elevat-

ed interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin

Infect Dis. https://doi.org/10.1093/cid/ciaa449

9. Ulhaq ZS, Soraya GV (2020) Interleukin-6 as a potential biomarker

of COVID-19 progression. Med Mal Infect 50:382–383

10. Zhang Y, Zhang Z, Wei R et al (2020) IL (interleukin)-6 contributes

to deep vein thrombosis and is negatively regulated by miR-338-5p.

Arterioscler Thromb Vasc Biol 40:323–334

11. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z (2020) Anticoagulant

treatment is associated with decreased mortality in severe corona-

virus disease 2019 patients with coagulopathy. J Thromb Haemost.

https://doi.org/10.1111/jth.14817

12. Klok FA, Kruip MJHA, van der Meer NJM et al (2020) Incidence

of thrombotic complications in critically ill ICU patients with

COVID-19. Thromb Res. https://doi.org/10.1016/j.thromres.2020.

04.013

13. Geyer LL, Scherr M, Körner M et al (2012) Imaging of acute

pulmonary embolism using a dual energy CT system with rapid

kVp switching: initial results. Eur J Radiol 81:3711–3718

14. Bernheim A, Mei X, Huang M et al (2020) Chest CT findings in

coronavirus disease-19 (COVID-19): relationship to duration of

infection. Radiology. https://doi.org/10.1148/radiol.2020200463

15. British Society of Thoracic Imaging (2020) Thoracic imaging in

COVID 19 infection. Guidance for the Reporting Radiologist

(2nd version). Available via https://www.bsti.org.uk/media/

resources/files/BSTI_COVID-19_Radiology_Guidance_version_

2_16.03.20.pdf. Accessed 20 March 2020

16. Caruso D, Zerunian M, Polici M et al (2020) Chest CT features of

COVID-19 in Rome, Italy. Radiology. https://doi.org/10.1148/

radiol.2020201237

17. Idilman IS, Dizman GT, Duzgun SA et al (2020) Lung and kidney

perfusion deficits diagnosed by dual-energy computed tomography

in patients with COVID-19 related systemic microangiopathy. Eur

Radiol. https://doi.org/10.1007/s00330-020-07155-3

18. Rubin GD, Ryerson CJ, Haramati LB et al (2020) The role of chest

imaging in patient management during the COVID-19 pandemic: a

multinational consensus statement from the Fleischner Society.

Chest. https://doi.org/10.1016/j.chest.2020.04.003

19. Zhang B, Zhou X, Qiu Y et al (2020) Clinical characteristics of 82

death cases with COVID-19. medRxiv. https://doi.org/10.1101/

2020.02.26.20028191

20. Gervaise A, Bouzad C, Peroux E, Helissey C (2020) Acute pulmo-

nary embolism in non-hospitalized COVID-19 patients referred to

CTPA by emergency department. Eur Radiol. https://doi.org/10.

1007/s00330-020-06977-5

21. Wieslander B, Ramos JG, Ax M, Petersson J, Ugander M (2019)

Supine, prone, right and left gravitational effects on human pulmo-

nary circulation. J Cardiovasc Magn Reson 21:69

Publisher’snoteSpringer Nature remains neutral with regard to jurisdic-

tional claims in published maps and institutional affiliations.

Eur Radiol

Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach

Article

Full-text available

May 2024

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.

D-Dimers in diagnosis and prevention of venous thrombosis: recent advances and their practical implications

Article

Full-text available

Nov 2023
Pol Arch Med Wewn

D‑Dimers derive from degradation of cross‑linked fibrin by plasmin, and thus their level is a marker of coagulation and fibrinolytic system activation. Guidelines recommend that D‑dimers are determined if the pretest probability (PTP) is low or intermediate, to exclude venous thromboembolism (VTE), either deep vein thrombosis or pulmonary embolism, and to avoid imaging tests. If the PTP is high or D‑dimer level is above the suggested thresholds, imaging is recommended. D‑Dimer assays offer high sensitivity and low specificity, as D‑dimer levels can be above the threshold in several other conditions than thrombosis, and they increase with age. As a result, there have been several proposals to improve the diagnostic accuracy of D‑dimer levels by adjusting the cutoffs according to patient characteristics, such as age, PTP, pregnancy, renal function, or cancer. D‑Dimer levels can also predict clinical severity of COVID‑19, and escalated anticoagulation based on D‑dimer levels can be associated with a lower risk of mortality in patients with severe COVID‑19. Finally, D‑dimer levels have been incorporated in prediction models for recurrent VTE to help identify patients who may benefit from prolonged anticoagulation.

COVID-19-Associated Pulmonary Embolism: Facts and Fallacies

Article

Jan 2023

Alcibey Alvarado González

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

Preprint

Full-text available

Feb 2023

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

Article

Full-text available

Mar 2023

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.

CORRELATION BETWEEN THE CT SEVERITY SCORE OF COVID-19 PNEUMONIA AND PULMONARY EMBOLISM

Article

Jan 2023

Objectives: To correlate the lung parenchymal involvement in COVID-19 patients and the incidence of thrombosis, determine type of thrombosis and the level of pulmonary system involved. Computed Tomography Pulmonary Angiography (CTPA) was Methods: performed in 50 COVID19 positive patients. The patients were stratied into positive and negative for thrombosis. The type of thrombosis, level of the pulmonary system involvement and other factors like d-dimer levels and presence of co-morbidities were taken into account in patients who had thrombosis. Results: There is an increased incidence of thrombosis among the patients with higher severity of COVID-19, increased d-dimer levels and presence of comorbidities. Amongst the arterial system, the segmental branches were most commonly involved and partial thrombosis was the most commonly encountered type of thrombosis. Increased severity of COVID-19 pneumonia along with other fac Conclusion: tors like elevated d-dimer levels and presence of comorbidities lead to an increased incidence of thrombosis in patients with COVID-19 pneumonia

Lung Ventilation-Perfusion Scan in COVID-19 Various Patterns of Perfusion Defects

Article

Jan 2023

Although COVID-19 infection is associated with the increased risk of pulmonary thromboembolism (PTE), COVID-19 pulmonary lesions cause ventilation-perfusion (V/Q) patterns other than PTE. Although extensive research has been done to address different anatomical patterns of COVID-19, there is a knowledge gap in terms of V/Q lung scintigraphy in these patients. The purpose of this study is to demonstrate these patterns and to show how important it is to use SPECT/CT in addition to planar images to differentiate between these patterns from PTE. In the current collection , we presented various patterns of V/Q SPECT/CT abnormalities in COVID-19 patients.

The Relationship Between Pulmonary Artery Diameter Measured by Chest CT and D-Dımer in COVID-19 Patients Admitted to the Emergency Department

Article

Mar 2024

Aim The coronavirus disease 2019 (COVID-19) pandemic has become a global health emergency due to its rapid spread worldwide. Our study evaluated the relationship between pulmonary artery diameter and d-dimer in COVID-19 patients. Material and Methods Patients aged 18 years and older with International Classification of Diseases 10 diagnosis code U07.3 who were admitted to our emergency department between March 15, 2020, and November 31, 2020, were included in our study. Demographic data (age, sex), laboratory tests (polymerase chain reaction test, d-dimer level), and imaging results (chest computed tomography, computed tomography pulmonary angiography) of the patients were retrospectively analyzed using medical records and the hospital electronic record system. Results A total of 1654 patients were included in the study. The 30-day mortality rate was 13.7% (n=227). The most effective independent variable on 30-day mortality was 44 years of age or older. Pulmonary artery diameter and d-dimer levels were found to be higher in both the group with typical COVID-19 chest computed tomography findings and in patients who died within 30 days. However, unlike the literature, there was no significant difference in pulmonary artery diameter and d-dimer levels between patients with and without pulmonary embolism. Conclusion In conclusion, we found a weak positive correlation between d-dimer and pulmonary artery diameter in COVID-19 patients. Keywords: COVID-19, d-dimer, pulmonary artery

Incidence and severity of pulmonary embolism in COVID-19 infection: Ancestral, Alpha, Delta, and Omicron variants

Article

Full-text available

Dec 2023

Little information is available regarding incidence and severity of pulmonary embolism (PE) across the periods of ancestral strain, Alpha, Delta, and Omicron variants. The aim of this study is to investigate the incidence and severity of PE over the dominant periods of ancestral strain and Alpha, Delta, and Omicron variants. We hypothesized that the incidence and the severity by proximity of PE in patients with the newer variants and vaccination would be decreased compared with those in ancestral and earlier variants. Patients with COVID-19 diagnosis between March 2020 and February 2022 and computed tomography pulmonary angiogram performed within a 6-week window around the diagnosis (−2 to +4 weeks) were studied retrospectively. The primary endpoints were the associations of the incidence and location of PE with the ancestral strain and each variant. Of the 720 coronavirus disease 2019 patients with computed tomography pulmonary angiogram (58.6 ± 17.2 years; 374 females), PE was diagnosed among 42/358 (12%) during the ancestral strain period, 5/60 (8%) during the Alpha variant period, 16/152 (11%) during the Delta variant period, and 13/150 (9%) during the Omicron variant period. The most proximal PE (ancestral strain vs variants) was located in the main/lobar arteries (31% vs 6%–40%), in the segmental arteries (52% vs 60%–75%), and in the subsegmental arteries (17% vs 0%–19%). There was no significant difference in both the incidence and location of PE across the periods, confirmed by multivariable logistic regression models. In summary, the incidence and severity of PE did not significantly differ across the periods of ancestral strain and Alpha, Delta, and Omicron variants.

Quantitative chest CT imaging characteristics and outcome of patients with COVID-19 associated pulmonary artery thrombosis: A single-center retrospective cohort study

Article

Jul 2023
MEDICINE

Coronavirus disease 2019 (COVID-19)-associated pulmonary thrombotic events occur frequently and are associated with disease severity and worse clinical outcomes. We aimed to describe the clinical and quantitative chest computed tomography (CT) imaging characteristics based on density ranges (Hounsfield units) and the outcomes of patients with COVID-19 associated pulmonary artery thrombosis. This retrospective cohort study included all patients with COVID-19 hospitalized in a tertiary care hospital between March 2020 and June 2022 who underwent a CT pulmonary angiography. We included 73 patients: 36 (49.3%) with and 37 (50.7%) without pulmonary artery thrombosis. The in-hospital all-cause mortality was 22.2 versus 18.9% ( P = .7), and the intensive care unit admission rates were 30.5 versus 8.1% ( P = .01) at the time of diagnosis of pulmonary artery thrombosis. Except for D-dimers (median of 3142 vs 533, P = .002), the other clinical, coagulopathy, and inflammatory markers were similar. Logistic regression analysis revealed that only D-dimers were associated with pulmonary artery thrombosis ( P = .012). ROC curve analysis of D-dimers showed that a value greater than 1716 ng/mL predicted pulmonary artery thrombosis with an area under the curve of 0.779, 72.2% sensitivity, and 73% specificity (95% CI 0.672-0.885). Peripheral distribution of pulmonary artery thrombosis was recorded in 94.5% of cases. In the lower lobes of the lungs, the incidence of pulmonary artery thrombosis was 6 times higher than that in the upper lobes (58-64%), with a percentage of lung injury of 80% to 90%. Analysis of the distribution of arterial branches with filling defects revealed that 91.6% occurred in lung areas with inflammatory lesions. Quantitative chest CT imaging provides valuable information regarding the extent of COVID-19 associated lung damage and can be used to anticipate the co-location of pulmonary immunothrombotic events. In patients with severe COVID-19, in-hospital all-cause mortality was similar regardless of the presence of associated distal pulmonary thrombosis.

Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study

Article

Full-text available

Dec 2020
BMC INFECT DIS

Background COVID-19 is highly contagious, and the crude mortality rate could reach 49% in critical patients. Inflammation concerns on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods In this cross-sectional study, 100 patients were included and divided into mild, severe or critical groups according to disease condition. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. Results Significantly, disease severity was associated with age (R = -0.564, P < 0.001), interleukin-2 receptor (IL2R) (R = -0.534, P < 0.001), interleukin-6 (IL-6) (R = -0.535, P < 0.001), interleukin-8 (IL-8) (R = -0.308, P < 0.001), interleukin-10 (IL-10) (R = -0.422, P < 0.001), tumor necrosis factor α (TNFα) (R = -0.322, P < 0.001), C-reactive protein (CRP) (R = -0.604, P < 0.001), ferroprotein (R = -0.508, P < 0.001), procalcitonin (R = -0.650, P < 0.001), white cell counts (WBC) (R = -0.54, P < 0.001), lymphocyte counts (LC) (R = 0.56, P < 0.001), neutrophil count (NC) (R = -0.585, P < 0.001) and eosinophil counts (EC) (R = 0.299, P < 0.001). With IL2R > 793.5 U/mL or CRP > 30.7 ng/mL, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Conclusions Inflammation is closely related to severity of COVID-19, and IL-6 and TNFα might be promising therapeutic targets.

Lung and kidney perfusion deficits diagnosed by dual-energy computed tomography in patients with COVID-19-related systemic microangiopathy

Article

Full-text available

Aug 2020

Objectives There is increasing evidence that thrombotic events occur in patients with coronavirus disease (COVID-19). We evaluated lung and kidney perfusion abnormalities in patients with COVID-19 by dual-energy computed tomography (DECT) and investigated the role of perfusion abnormalities on disease severity as a sign of microvascular obstruction.Methods Thirty-one patients with COVID-19 who underwent pulmonary DECT angiography and were suspected of having pulmonary thromboembolism were included. Pulmonary and kidney images were reviewed. Patient characteristics and laboratory findings were compared between those with and without lung perfusion deficits (PDs).ResultsDECT images showed PDs in eight patients (25.8%), which were not overlapping with areas of ground-glass opacity or consolidation. Among these patients, two had pulmonary thromboembolism confirmed by CT angiography. Patients with PDs had a longer hospital stay (p = 0.14), higher intensive care unit admission rates (p = 0.02), and more severe disease (p = 0.01). In the PD group, serum ferritin, aspartate aminotransferase, fibrinogen, D-dimer, C-reactive protein, and troponin levels were significantly higher, whereas albumin level was lower (p < 0.05). D-dimer levels ≥ 0.485 μg/L predicted PD with 100% specificity and 87% sensitivity. Renal iodine maps showed heterogeneous enhancement consistent with perfusion abnormalities in 13 patients (50%) with lower sodium levels (p = 0.03).Conclusions We found that a large proportion of patients with mild-to-moderate COVID-19 had PDs in their lungs and kidneys, which may be suggestive of the presence of systemic microangiopathy with micro-thrombosis. These findings help in understanding the physiology of hypoxemia and may have implications in the management of patients with COVID-19, such as early indications of thromboprophylaxis or anticoagulants and optimizing oxygenation strategies.Key Points • Pulmonary perfusion abnormalities in COVID-19 patients, associated with disease severity, can be detected by pulmonary DECT. • A cutoff value of 0.485 μg/L for D-dimer plasma levels predicted lung perfusion deficits with 100% specificity and 87% sensitivity (AUROC, 0.957). • Perfusion abnormalities in the kidney are suggestive of a subclinical systemic microvascular obstruction in these patients.

Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department

Article

Full-text available

Jun 2020

Objectives To evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department.Methods From March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified. Relevant clinical and laboratory data and CT scan findings were collected for each patient. CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE. Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group.ResultsAPE was identified in 13 (18%) CTPA scans. The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs. 59.6 years, p = 0.008, and 7.29 vs. 3.29 μg/ml, p = 0.011). There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs. 78%), CT severity score (6.3 vs. 7.1, p = 0.365), quality of CTPA (1.8 vs. 2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146).Conclusions Non-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE. The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia.Key Points • Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA. Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism. • Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type. • Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.

CO-RADS – A categorical CT assessment scheme for patients with suspected COVID-19: definition and evaluation

Article

Full-text available

Apr 2020

Purpose To introduce the COVID-19 Reporting and Data System (CO-RADS) for standardized assessment of pulmonary involvement of COVID-19 on non-enhanced chest CT and report its initial interobserver agreement and performance. Methods The Dutch Radiological Society (NVvR) developed CO-RADS based on other efforts for standardization, such as Lung-RADS or BI-RADS. CO-RADS assesses the suspicion for pulmonary involvement of COVID-19 on a scale from 1 (very low) to 5 (very high). The system is meant to be used in patients presenting with moderate to severe symptoms of COVID-19. The system was evaluated using 105 chest CTs of patients admitted to the hospital with clinical suspicion of COVID-19 in whom RT-PCR was performed (62 +/- 16 years, 61 men, 53 with positive RT-PCR). Eight observers assessed the scans using CO-RADS. Fleiss' kappa was calculated, and scores of individual observers were compared to the median of the remaining seven observers. The resulting area under the receiver operating characteristics curve (AUC) was compared to results from RT-PCR and clinical diagnosis of COVID-19. Results There was absolute agreement among observers in 573 (68.2%) of 840 observations. Fleiss' kappa was 0.47 (95% confidence interval (CI) 0.45-0.47), with the highest kappa for CO-RADS categories 1 (0.58, 95% CI 0.54-0.62) and 5 (0.68, 95% CI 0.65-0.72). The average AUC was 0.91 (95% CI 0.85-0.97) for predicting RT-PCR outcome and 0.95 (95% CI 0.91-0.99) for clinical diagnosis. The false negative rate for CO-RADS 1 was 9/161 (5.6%, 95% CI 1.0-10%), and the false positive rate for CO-RADS 5 was 1/286 (0.3%, 95% CI 0-1.0%). Conclusions CO-RADS is a categorical assessment scheme for pulmonary involvement of COVID-19 on non-enhanced chest CT providing very good performance for predicting COVID-19 in patients with moderate to severe symptoms and has a substantial interobserver agreement, especially for categories 1 and 5.

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Article

Full-text available

Apr 2020
CLIN INFECT DIS

Background: Although the detection of SARS-CoV-2 viral load in respiratory specimens has been widely used to diagnose coronavirus disease-19 (COVID-19), it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of COVID-19 patients. However, it is not clear whether testing for RNAaemia is correlated with the occurrence of cytokine storms or with the specific class of patients. Methods: This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the "Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition)" issued by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load and IL-6 levels were determined. . Results: Clinical characteristics analysis of 48 cases of COVID-19 showed that RNAaemia was diagnosed only in the critically ill group and seemed to reflect the severity of the disease. Furthermore, the level of inflammatory cytokine IL-6 in critically ill patients increased significantly, almost 10 times that in other patients. More importantly, the extremely high IL-6 level was closely correlated with the detection of RNAaemia (R = 0.902). Conclusions: Detectable serum SARS-Cov-2 RNA(RNAaemia) in COVID-19 patients was associated with elevated IL-6 concentration and poor prognosis. Because the elevated IL-6 may be part of a larger cytokine storm which could worsen outcome, IL-6 could be a potential therapeutic target for critically ill patients with an excessive inflammatory response.

The Role of Chest Imaging in Patient Management During the COVID-19 Pandemic: A Multinational Consensus Statement From the Fleischner Society

Article

Full-text available

Apr 2020

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.

Chest CT Features of COVID-19 in Rome, Italy

Article

Full-text available

Apr 2020

Background The standard for diagnosis of SARS-CoV-2 virus is reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of COVID-19 pneumonia. Purpose To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with RT-PCR. Methods In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients with suspected COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were: chest CT with contrast medium performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as reference. Chest CT features were calculated in a subgroup of RT-PCR-positive and CT-positive patients. CT features of hospitalized patients and patient in home isolation were compared by using Pearson chi squared test. Results Our study population comprised 158 consecutive study participants (83 male and 75 female, mean age 57 y ±17). Fever was observed in 97/158 (61%), cough in 88/158 (56%), dyspnea in 52/158 (33%), lymphocytopenia in 95/158 (60%), increased C-reactive protein level in 139/158 (88%), and elevated lactate dehydrogenase in 128/158 (81%) study participants. Sensitivity, specificity, and accuracy of CT were 97% (60/62)[95% IC, 88-99%], 56% (54/96)[95% IC,45-66%] and 72% (114/158)[95% IC 64-78%], respectively. In the subgroup of RT-PCR-positive and CT-positive patients, ground-glass opacities (GGO) were present in 58/58 (100%), multilobe and posterior involvement were both present in 54/58 (93%), bilateral pneumonia in 53/58 (91%), and subsegmental vessel enlargement (> 3 mm) in 52/58 (89%) of study participants. Conclusion The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripherally ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (> 3 mm). Chest CT sensitivity was high (97%) but with lower specificity (56%).

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Article

Full-text available

Mar 2020
J THROMB HAEMOST

Background A relatively high mortality of severe coronavirus disease 2019 (COVID‐19) is worrying, the application of heparin in COVID‐19 has been recommended by some expert consensus due to the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. Methods Coagulation results, medications and outcomes of consecutive patients being classified as severe COVID‐19 in Tongji hospital were retrospectively analysed. The 28‐day mortality between heparin users and nonusers were compared, also in different risk of coagulopaphy which was stratified by the sepsis‐induced coagulopathy (SIC) score or D‐dimer result. Results There were 449 patients with severe COVID‐19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin, LMWH) for 7 days or longer. The D‐dimer, prothrombin time and age were positively, and platelet count was negatively, correlated with 28‐day mortality in multivariate analysis. No difference on 28‐day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P=0.910). But the 28‐day mortality of heparin users were lower than nonusers In patients with SIC score ≥4 (40.0% vs 64.2%, P=0.029), or D‐dimer > 6 fold of upper limit of normal (32.8% vs 52.4%, P=0.017). Conclusions Anticoagulant therapy mainly with LMWH appears to be associated with better prognosis in severe COVID‐19 patients meeting SIC criteria or with markedly elevated D‐dimer.

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Article

Apr 2020
THROMB RES

Introduction COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. Reports on the incidence of thrombotic complications are however not available. Methods We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital. Results We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020. All patients received at least standard doses thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications. Conclusion The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high. Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

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