Non-invasive Prognostication of COVID-19 Patients by Use of Biomarkers in Exhaled Breath Condensate (VTE-COVID-19)

The main objective of this study is to assess if analysis of exhaled breath condensate (EBC) can provide useful prognostic markers for admission to the intensive care unit (ICU) due to acute respiratory insufficiency among patients with Coronavirus disease 2019 (COVID-19). Additionally, to give a characterization of the lung damage caused by COVID-19 by analysis of daily blood samples.

The hypothesis is that the protein content of the EBC from COVID-19 patients who require admission to the ICU differs from the EBC from COVID-19 patients with uncomplicated hospitalization, potentially providing diagnostic markers of COVID-19 related pulmonary damage.

Study Overview

• Status: Completed
• Conditions: Covid19; Corona Virus Infection

Detailed Description

Two EBC samples will be collected from each study participant; a baseline sample (at admission) and a sample at either hospital discharge or transfer to the ICU. In addition, blood samples will be collected in order to investigate the pathophysiology of COVID-19 using metabolomics analysis, and for standardization and validation of the putative markers from the EBC.

The investigators will collect EBC from COVID-19 positive patients acutely admitted to Aalborg University Hospital due to COVID-19 symptoms and compare the protein and metabolite profiles in patients, who are treated at the ward with patients, who are transferred to the ICU for mechanical ventilation. The main-outcome (i.e. means of the relative amounts of specific proteins in the EBC samples) will be compared by unpaired t-tests after assessment of normality and standard deviations within the two groups in the following comparison: EBC collected at admission (baseline) from patients who did not need mechanical ventilation vs. EBC at admission from patients who did need mechanical ventilation. Paired t-tests will compare the proteins in baseline EBC samples and samples at either transfer to the ICU intubation or discharge to home in order to describe the pathophysiology in the two groups (no ICU need versus need of ICU admission). The investigators will not collect EBC from patients admitted to the ICU for open-circuit respiratory support, e.g. high-flow oxygenation; these patients will be asked to give an EBC sample before discharge, like the patients who did not need ICU care.

A blood sample will be drawn at the two days of EBC collection (i.e. a 9 mL tube drawn along with routine work-up blood samples) from the study participants for two purposes: 1) Standardization of the putative markers and verification and supplementing analysis of the EBC markers. In order to qualify the most suitable markers and substrates for standardization, the analysis of the EBC samples must be completed before the blood samples can be analyzed. Conventional biochemical analysis will be used for this purpose. 2) Pathophysiological description of patients hospitalized with COVID-19 using metabolomics and proteomics analysis. No genetic analysis will be conducted on the stored blood samples.

After collection of the EBC, the samples will be stored directly in the collection tube marked with study subject id at -80⁰C. The EBC samples will be used solely for the subsequent analysis of the protein composition (i.e. proteomics) and metabolites (i.e. metabolomics).

The collection of EBC will not lead to deviations from standard diagnostic procedures or treatments. The patients will have routine blood samples drawn as a part of the diagnostic work-up and daily disease monitoring. The investigators will ask for consent to draw an extra 9 mL blood sample along with the routine blood samples at the two days of EBC collection.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

COVID-19 positive patients acutely admitted to Aalborg University Hospital due to COVID-19 symptoms.

Description

Inclusion Criteria:

• Age ≥18 years and admitted at Aalborg Hospital with confirmed COVID-19
• Need for hospitalization due to COVID-19 symptoms.
• Able to provide informed consent

Exclusion Criteria:

• Need for vasopressor therapy, mechanical ventilation, extracorporal circulation, or dialysis at admission

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of admission to ICU in hospitalized COVID-19 patients	The primary outcome is prediction of admission to ICU in hospitalized COVID-19 patients by use of one or more novel biomarkers in the EBC	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathophysiology in COVID-19 patients	In a sub-study, we will collect the daily blood samples for analysis in order to investigate the pathophysiology in COVID-19, and for standardization and validation of putative EBC markers in the blood.	1 year

Collaborators and Investigators

• Sponsor: Inger Lise Gade
• Collaborators: Aarhus University Hospital Skejby
• Investigators: Principal Investigator: Inger L Gade, MD, PhD, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2020
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Exhaled breath condensate
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: ILG-VTE-COVID-19-2020; N-20200069 (Other Identifier: Den Videnskabsetiske Komite for Region Nordjylland)

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