Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Subscriptions

In vivo demonstration of pulmonary microvascular involvement in COVID-19 using Dual-Energy Computed Tomography

Salim Si-Mohamed, Nader Chebib, Monica Sigovan, Lea Zumbihl, Ségoléne Turquier, Sara Boccalini, Loic Boussel, Jean-Francois Mornex, Vincent Cottin, Philippe Douek
European Respiratory Journal 2020; DOI: 10.1183/13993003.02608-2020
Salim Si-Mohamed
1Radiology Department, Hospices Civils de Lyon, CHU Louis Pradel, Lyon, France
2Claude Bernard Lyon 1 University, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Salim Si-Mohamed
Nader Chebib
3Pneumology Department, Hospices Civils de Lyon, National Reference Center for Rare, Bron, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monica Sigovan
2Claude Bernard Lyon 1 University, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lea Zumbihl
1Radiology Department, Hospices Civils de Lyon, CHU Louis Pradel, Lyon, France
4Claude Bernard Lyon 1 University, University of Lyon, INRA, UMR754, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ségoléne Turquier
3Pneumology Department, Hospices Civils de Lyon, National Reference Center for Rare, Bron, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sara Boccalini
1Radiology Department, Hospices Civils de Lyon, CHU Louis Pradel, Lyon, France
2Claude Bernard Lyon 1 University, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Loic Boussel
1Radiology Department, Hospices Civils de Lyon, CHU Louis Pradel, Lyon, France
2Claude Bernard Lyon 1 University, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Francois Mornex
3Pneumology Department, Hospices Civils de Lyon, National Reference Center for Rare, Bron, France
4Claude Bernard Lyon 1 University, University of Lyon, INRA, UMR754, Lyon, France
5Pulmonary Diseases, Competence Center for severe pulmonary hypertension, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Cottin
3Pneumology Department, Hospices Civils de Lyon, National Reference Center for Rare, Bron, France
4Claude Bernard Lyon 1 University, University of Lyon, INRA, UMR754, Lyon, France
5Pulmonary Diseases, Competence Center for severe pulmonary hypertension, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vincent Cottin
Philippe Douek
1Radiology Department, Hospices Civils de Lyon, CHU Louis Pradel, Lyon, France
2Claude Bernard Lyon 1 University, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

In Covid-19 pneumonia, dual-energy computed tomography has shown two patterns of lung perfusion along the course of the disease: an increase in perfusion blood volume (PBV) with ground glass opacities and a decrease in PBV with consolidation.

To the Editor,

Vascular involvement in coronavirus disease 2019 (Covid-19) has been suggested by several observations such as the high rate of pulmonary embolism [1], the prothrombotic state and the proinflammatory biological profile [2, 3] as well as the pathological findings of severe endothelial injury and diffuse thrombosis [4]. Dual-energy computed tomography (DECT) allows specific imaging of the iodinated contrast agent distribution within the lung, which has been demonstrated as a surrogate marker of lung perfusion [5, 6]. Therefore, our goal was to assess in vivo pulmonary microvascular involvement in patients with Covid-19 pneumonia by using DECT and to determine whether vascular changes vary during the course of the disease.

This monocentric study was approved by our institutional ethics committee. We performed a retrospective analysis of patients hospitalised for Covid-19 pneumonia (confirmed by RT-PCR for SARS-COV-2) who underwent enhanced DECT for clinical worsening of symptoms and/or hypoxemia in search of pulmonary embolism.

Lung CT angiography data were acquired on a dual-layer dual energy CT system (iQon®; Philips Healthcare) using a bolus-tracking technique with a threshold of 110 HU in the main pulmonary artery enabling iodine images reconstruction, and reviewed by a senior radiologist and a senior pulmonologist. Predominant lung lesions such as ground glass opacities (GGO) and alveolar consolidation as well as their volumetric extension per lobe (0: none, 1: 0–25%, 2: 26–50%, 3: 51–75%, 4: 76–100%) were rated. Presence and aspect of perfusion abnormalities were evaluated per lobe as an increase or decrease of perfusion blood volume (PBV) compared to the remote parenchyma. Lobar PBV was indexed to iodine concentration in the pulmonary trunk, by calculating the ratio of mean iodine concentration in a lobe to that in the pulmonary trunk. As lung perfusion may depend of the injection time, iodine concentrations ratios in the main pulmonary artery over the left atrium were recorded and expressed as median (IQ1-IQ3).

PBV distribution was tested for normality using d'Agostino-Pearson test. Student unpaired t-test was used for PBV comparisons between lobes with predominant GGO and consolidation. A multiple linear regression was used to compare the lobar PBV between parenchymal type lesions as a function of the extension. Statistical significance was set at p<0.05.

Five patients were included between March 15 and April 30, 2020. All of them were men and median age was 70 years (range: 45–88). No patient had a history of chronic respiratory disease. Three patients (60%) were admitted to the intensive care unit and 1 patient (20%) died of acute respiratory failure. At the time of DECT imaging, 4 patients (80%) had oxygen supplementation therapy (oxygen saturation<90% on room air), 2 patients (40%) had prophylactic anticoagulation therapy, while the remaining 3 (60%) had long-term therapeutic anticoagulant doses. No patient had evidence of bacterial infection. Concurrently, D-Dimers levels were 3107±3053 μg·L−1, fibrinogen levels were 6.5±1.6 g·L−1, C-reactive protein levels were 93±45 mg·L−1 and platelet count was 390 000±234 000 mm−3.

DECT was performed during the first week from the onset of symptoms in 2 patients (Day 7 and 8) and after 2 weeks in 3 patients (Day 17 and 18). No patient had pulmonary embolism. Patients in the early clinical phase had predominant GGO lesions (fig. 1a) while patients in the late clinical phase had predominant consolidation (fig. 1b). Median ratio of iodine concentration between main pulmonary artery and left atrium were calculated at 1.4 (1.3–3.1). Perfusion abnormalities were found in all lobes matching with corresponding parenchymal lesions. Mean±sd PBV was 0.48±0.09 in lobes with predominant GGO and 0.22±0.08 in lobes with predominant consolidation (p<0.0001). No perfusion abnormalities were found in the areas surrounding the lesions nor in the normal parenchymal areas. Multiple linear regression analysis demonstrated a significant correlation between PBV and parenchymal lesions (R=0.84, p<0.0001), with a positive coefficient between PBV and GGO (Pearson's r: 0.83) and a negative coefficient between PBV and consolidation (Pearson's r: −0.51) (fig. 1c).

FIGURE 1
  • Download figure
  • Open in new tab
  • Download powerpoint
FIGURE 1

Key imaging features of microvascular involvement in COVID-19 using lung angiography dual-energy CT scans. Perfusion blood volume (PBV) is defined as the ratio between iodine concentration in a pulmonary lobe over iodine concentration in the main pulmonary artery. a) Representative imaging features of the early clinical phase: increased perfusion blood volume (PBV) is seen (black arrows, right panel), matching with ground glass opacities (GGO)(black arrows, left panel), relatively to the areas without GGO. b) Representative imaging features of the late clinical phase: decreased PBV is seen (white arrows, right panel), matching with alveolar consolidation (black arrows, left panel), relatively to the areas without condensation. c) 3D graph of lobar PBV as a function of the presence and extension of GGO and alveolar consolidation. Each dot corresponds to a lobe, the coordinates of which are represented by PBV in the z axis, GGO extension in x axis and consolidation extension in y axis (volumetric extension score, 0: none, 1: 0–25%, 2: 26–50%, 3: 51–75%, 4: 76–100%). Color grid represents the multiple linear regression plane.

This pilot study has demonstrated that DECT may be used to assess pulmonary vascular involvement in vivo in patients with Covid-19 pneumonia. Two different patterns of lung perfusion were observed.

In the early clinical phase occurring in the first week since the onset of symptoms, the predominant parenchymal lesions were diffuse bilateral GGO and were associated with increased lung perfusion in the corresponding lobes. This observation suggests that hypoxemia in these patients may be due to a ventilation/perfusion mismatch causing pulmonary shunting. We speculate that low ventilation/perfusion ratio may be related to decreased ventilation secondary to viral pneumonia, along with normal or increased perfusion which might be due to the loss of the physiological hypoxic vasoconstriction provoked by inflammatory cytokines. These vascular changes may correspond to the histopathological findings of intussusceptive angiogenesis found in a recent autopsy study [4].

During the later phase of the disease, occurring after 2 weeks, the predominant parenchymal lesions were bilateral alveolar consolidation and were associated with decreased lung perfusion in the affected lobes. The presence of lung hypoperfusion in the absence of detectable pulmonary embolism is a distinctive hallmark of Covid-19 and could be due to the endothelial dysfunction and the release of prothrombotic cytokines, often referred to as « the cytokine storm » and potentially leading to acute respiratory distress syndrome. These vascular changes are corroborated by pathological findings of endothelial dysfunction, diffuse coagulopathy affecting small vessels and the formation of microthrombi [4]. All patients had increased inflammatory and prothrombotic biomarkers. It is also noteworthy that hypoperfusion lesions occurred despite anticoagulant therapy. Of note, description of pulmonary vascular manifestations of Covid-19 pneumonia using DECT has been previously reported [7, 8]. Radiological findings were mosaic perfusion patterns, vessel enlargement within and outside of lung opacities as well as peripheral perfusion defects with surrounding halos of increased perfusion [7, 8]. These results are to a certain extent consistent with our findings. However, our study provides new insights on chronological changes in the pulmonary perfusion along the course of the disease and in relation with parenchymal CT features [9, 10].

There are limitations to our study including the small number of patients and the retrospective design. Despite the predominant opacification of the pulmonary arteries of the DECT scans, the potential participation of a systemic arterial supply within areas of pneumonia cannot be ruled out. There were no sequential DECT done in the same patient. However, CT scans were conducted for « real life » clinical purposes, taking into consideration renal and radiation risks.

Conclusion

DECT imaging demonstrated pulmonary microvascular involvement in Covid-19 pneumonia with two distinctive patterns. It may be used to better understand Covid-19 pathophysiology and herald new targets for therapeutic trials.

Acknowledgements

We thank Dr. Valerie Leitman (University of Lyon) for their contributions to manuscript editing, Dr. Adeline Mansuy (Hospices civils de Lyon) for the research proposal submission.

Footnotes

  • Conflict of interest: Dr. Si-Mohamed reports personal fees from Boehringer Ingelheim and non-financial support from Guerbet, outside the submitted work.

  • Conflict of interest: Dr. Chebib reports non-financial support from CSL Behring, Actelion, GSK, Boehringer Ingelheim, Roche and MSD, outside the submitted work.

  • Conflict of interest: Dr. Sigovan has nothing to disclose.

  • Conflict of interest: Dr. Zumbihl has nothing to disclose.

  • Conflict of interest: Dr. Turquier has nothing to disclose.

  • Conflict of interest: Dr. Boccalini has nothing to disclose.

  • Conflict of interest: Dr. Boussel has nothing to disclose.

  • Conflict of interest: Dr. Mornex reports grants, personal fees and non-financial support from CSL Behring, grants, personal fees and non-financial support from LFB, personal fees and non-financial support from Actelion, personal fees from Roche, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, personal fees from Chiesi and personal fees from Elivie, outside the submitted work.

  • Conflict of interest: Dr. Cottin reports personal fees and non-financial support from Actelion, grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Bayer / MSD, personal fees from Novartis, personal fees and non-financial support from Roche / Promedior, personal fees from Sanofi, personal fees from Celgene, personal fees from Galapagos, personal fees from Galecto, personal fees from Shionogi, personal fees from Astra Zeneca, personal fees from Fibrogen, outside the submitted work.

  • Conflict of interest: Dr. Douek has nothing to disclose.

  • Received July 2, 2020.
  • Accepted September 2, 2020.
  • Copyright ©ERS 2020
http://creativecommons.org/licenses/by-nc/4.0/

This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

References

  1. ↵
    1. Poyiadji N,
    2. Cormier P,
    3. Patel PY, et al.
    Acute Pulmonary Embolism and COVID-19. Radiology 2020: 201955. doi:10.1148/radiol.2020201955
  2. ↵
    1. Huang C,
    2. Wang Y,
    3. Li X, et al.
    Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506. doi:10.1016/S0140-6736(20)30183-5
    OpenUrlCrossRefPubMed
  3. ↵
    1. Zhou F,
    2. Yu T,
    3. Du R, et al.
    Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–1062. doi:10.1016/S0140-6736(20)30566-3
    OpenUrlCrossRefPubMed
  4. ↵
    1. Ackermann M,
    2. Verleden SE,
    3. Kuehnel M, et al.
    Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 2020: 383: 120–128. doi:10.1056/NEJMoa2015432
    OpenUrlCrossRefPubMed
  5. ↵
    1. Fuld MK,
    2. Halaweish AF,
    3. Haynes SE, et al.
    Pulmonary perfused blood volume with dual-energy CT as surrogate for pulmonary perfusion assessed with dynamic multidetector CT. Radiology 2013; 267: 747–756. doi:10.1148/radiol.12112789
    OpenUrlCrossRefPubMedWeb of Science
  6. ↵
    1. Si-Mohamed S,
    2. Moreau-Triby C,
    3. Tylski P, et al.
    Head-to-head comparison of lung perfusion with dual-energy CT and SPECT-CT. Diagn Interv Imaging 2020; 101: 299–310. doi:10.1016/j.diii.2020.02.006
    OpenUrl
  7. ↵
    1. Lang M,
    2. Som A,
    3. Carey D, et al.
    Pulmonary Vascular Manifestations of COVID-19 Pneumonia. Radiol Cardiothorac Imaging 2020; 2: e200277. doi:10.1148/ryct.2020200277
    OpenUrl
  8. ↵
    1. Lang M,
    2. Som A,
    3. Mendoza DP, et al.
    Hypoxaemia related to COVID-19: vascular and perfusion abnormalities on dual-energy CT. Lancet Infect Dis 2020.
  9. ↵
    1. Shi H,
    2. Han X,
    3. Jiang N, et al.
    Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020; 20: 425–434. doi:10.1016/S1473-3099(20)30086-4
    OpenUrlPubMed
  10. ↵
    1. Pan F,
    2. Ye T,
    3. Sun P, et al.
    Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19). Radiology 2020; 295: 715–721. doi:10.1148/radiol.2020200370
    OpenUrlPubMed
PreviousNext
Back to top
View this article with LENS
Vol 61 Issue 2 Table of Contents
European Respiratory Journal: 61 (2)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
In vivo demonstration of pulmonary microvascular involvement in COVID-19 using Dual-Energy Computed Tomography
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
In vivo demonstration of pulmonary microvascular involvement in COVID-19 using Dual-Energy Computed Tomography
Salim Si-Mohamed, Nader Chebib, Monica Sigovan, Lea Zumbihl, Ségoléne Turquier, Sara Boccalini, Loic Boussel, Jean-Francois Mornex, Vincent Cottin, Philippe Douek
European Respiratory Journal Jan 2020, 2002608; DOI: 10.1183/13993003.02608-2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
In vivo demonstration of pulmonary microvascular involvement in COVID-19 using Dual-Energy Computed Tomography
Salim Si-Mohamed, Nader Chebib, Monica Sigovan, Lea Zumbihl, Ségoléne Turquier, Sara Boccalini, Loic Boussel, Jean-Francois Mornex, Vincent Cottin, Philippe Douek
European Respiratory Journal Jan 2020, 2002608; DOI: 10.1183/13993003.02608-2020
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • To the Editor,
    • Conclusion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • SNPs identified by GWAS affecting asthma risk
  • Blood monocyte counts as a prognostic marker for IPF
  • Small airway dysfunction in HIV-infected never-smokers
Show more Research letter

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society