Vascular Abnormalities Detected With Chest CT in COVID-19 (COVID-CAVA)

Vascular Abnormalities Detected With Chest CT in COVID-19: Spectrum, Association With Other Lesions, and Correlation With Clinical Severity

Chest computed tomography of patients having coronavirus disease (COVID-19) will be analyzed with regards to vascular abnormalities (pulmonary embolism and vascular thickening), and their association with lung inflammation. The prevalence, severity, distribution, and prognostic value of chest CT findings will be assessed. Patients with vascular abnormalities will be compared to patients without, which is supposed to provide insights into the prognostic role of such abnormalities, and the potential impact on treatment strategy.

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumonia, Viral; Covid19; Pulmonary Embolism
• Intervention / Treatment: Diagnostic test: Chest CTA; Diagnostic test: Chest CT

Detailed Description

Since the SARS-CoV-2 outbreak, computed tomography (CT) imaging has almost immediately established itself as the primary non-invasive diagnostic tool for diagnosis, monitoring of COVID-19 pneumonia, and complications thereof.

While most of the currently available literature relies on non-contrast CT, the need to assess vascular abnormalities is being recognized as an increasingly important factor, both to help distinguish COVID-19 pneumonia from other viral infections, and to exclude pulmonary embolism (PE). Acute PE is believed to be a significant contributory factor in patients with adverse outcomes.

Relating to vascular changes other than PE, additional knowledge is required and not yet available to confirm and better understand early observations. In particular, a radiological sign referred to as "vascular thickening", "vascular enlargement", or "vascular congestion" that is thought to be a specific marker of COVID-19 pneumonia, calls for a thorough assessment. Quantitative analysis of this sign and correlation to clinical presentation is highly desirable.

The investigators will conduct a multicentric observational study in the form of a registry. For this purpose, each participating center needs to screen hundreds of COVID-19 patients to select those who meet the inclusion criteria and do not have any exclusion criteria. Then, clinical, laboratory and imaging data of eligible patients will be retrieved. The research will focus on the imaging manifestations of COVID-19 pneumonia and their relationship to vascular abnormalities within the lung; the potential association between such vascular abnormalities and COVID-19 clinical severity will be assessed.

To achieve adequate statistical power, the study needs to be multicentric, involving 7 Swiss institutions; CHUV Lausanne, USZ Zurich, USB Basel, Inselspital Bern, Division Stadt- und Landspitäler Inselgruppe, HUG Genève, HRC Rennaz. The following investigators are involved in this extensive nationwide effort:

• CHUV: Dr DC Rotzinger; Prof SD Qanadli; Prof PY Bochud; Prof L Alberio; Dr JL Pagani
• USZ: Prof H Alkadhi
• USB: Prof J Bremerich; Dr A Sauter
• Inselspital: Prof T Heverhagen; Prof L Ebner
• Division Stadt- und Landspitäler Inselgruppe: Prof A Christe
• HUG: Prof A Poletti
• HRC: Prof O Ratib

Intrahospital medical records, laboratory tests results, and data from chest CT performed in the participating centers between March 1st and July 31st, 2020 will be used to:

• assess the frequency of non-PE related vascular abnormalities on chest CT (vascular thickening), and their association with parenchymal opacities
• evaluate the rate of acute PE among the patients undergoing contrast-enhanced chest CT
• quantify the clot burden in terms of proximal or distal obstruction and quantitative CT obstruction index (CTOI) in patients with CT-proven PE
• evaluate the consequence of PE on pulmonary perfusion (distinguishing perfused vs. non-perfused pulmonary opacities) and cardiac morphology (right ventricle dilatation, reduced left atrial size)
• evaluate the correlation between pulmonary perfusion impairment and clinical severity

Using clinical, laboratory and CT imaging-derived variables, the investigators will perform outcome modelling to derive an integrative score to predict outcomes.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • CHUV

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients with positive rt-PCR for SARS-CoV-2 and chest CT (with or without intravenous contrast material injection) within the specified time frame.

Description

Inclusion Criteria:

• Patients admitted for COVID-19 (with positive rt-PCR for SARS-CoV-2) who had a contrast-enhanced chest CT within the specified timeframe.

Exclusion Criteria:

• Age <18 years Patients with another pre-existing infectious process Documented refusal of the reuse of medical data

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-CAVA PE; Patients with RT-PCR proven COVID-19 disease and CTA proven pulmonary embolism	Diagnostic test: Chest CTA; Chest CT with intravenous contrast material
COVID-CAVA non-PE; Patients with RT-PCR proven COVID-19 disease and no evidence of pulmonary embolism on CT	Diagnostic test: Chest CTA; Chest CT with intravenous contrast material; Diagnostic test: Chest CT; Chest CT without intravenous contrast material

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute pulmonary embolism	Incidence of acute pulmonary embolism (PE).	March 1st, 2020 to July 31st, 2020
Distribution of acute pulmonary embolism	Description of the anatomical distribution (lobar and segmental level)	March 1st, 2020 to July 31st, 2020
Pulmonary embolism clot burden	Description of the clot burden of acute pulmonary embolism (PE) using the CT obstruction index	March 1st, 2020 to July 31st, 2020
Association of pulmonary embolism with ground glass opacity	Rate of PE in segments with vs. without COVID-19 ground glass opacity	March 1st, 2020 to July 31st, 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome	Outcome will be registered in a categorical variable as outpatient, inpatient without intubation, inpatient with intubation, death	March 1st, 2020 to July 31st, 2020
D-dimers	D-dimer serum sampling (ng/mL), continuous variable	March 1st, 2020 to July 31st, 2020
PO2	Arterial blood oxygen partial pressure (PO2, mmHg), continuous variable	March 1st, 2020 to July 31st, 2020
SaO2	Venous blood oxygen saturation (SaO2, in %), continuous variable	March 1st, 2020 to July 31st, 2020
CRP	C-reactive protein serum sampling (mg/L), continuous variable	March 1st, 2020 to July 31st, 2020
Thrombocytes	Blood thrombocyte count (number per liter), continuous variable	March 1st, 2020 to July 31st, 2020
ICU admission	Rate of patients admitted in the intensive care unit (ICU)	March 1st, 2020 to July 31st, 2020
Alveolar opacity	Rate of lung segments with alveolar opacity	March 1st, 2020 to July 31st, 2020
Vascular congestion	Rate of lung segments with vascular congestion	March 1st, 2020 to July 31st, 2020
Vascular volume	Vascular volume measured at the segmental level (in mL), continuous variable	March 1st, 2020 to July 31st, 2020
Vein-to-artery ratio	The vein-to-artery ratio will be calculated at the segmental level (venous diameter [mm] / arterial diamter [mm]), continuous variable	March 1st, 2020 to July 31st, 2020

Collaborators and Investigators

• Sponsor: Salah D. Qanadli
• Collaborators: University of Zurich; University of Bern; University of Basel; University of Geneva, Switzerland

Publications and helpful links

General Publications

• Qanadli SD, Beigelman-Aubry C, Rotzinger DC. Vascular Changes Detected With Thoracic CT in Coronavirus Disease (COVID-19) Might Be Significant Determinants for Accurate Diagnosis and Optimal Patient Management. AJR Am J Roentgenol. 2020 Jul;215(1):W15. doi: 10.2214/AJR.20.23185. Epub 2020 Apr 7. No abstract available.
• Nevesny F, Rotzinger DC, Sauter AW, Loebelenz LI, Schmuelling L, Alkadhi H, Ebner L, Christe A, Platon A, Poletti PA, Qanadli SD. Acute Pulmonary Embolism in COVID-19: A Potential Connection between Venous Congestion and Thrombus Distribution. Biomedicines. 2022 Jun 2;10(6):1300. doi: 10.3390/biomedicines10061300.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): July 31, 2020
• Study Completion (Anticipated): March 31, 2021

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Computed tomography; COVID-19; Thromboembolism; Vascular abnormalities; Lung infection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Embolism and Thrombosis; COVID-19; Embolism; Congenital Abnormalities; Pneumonia, Viral; Pulmonary Embolism
• Other Study ID Numbers: 2020-1469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No