Non-invasive Detection of Pneumonia in Context of Covid-19 Using Gas Chromatography - Ion Mobility Spectrometry (GC-IMS)

• ClinicalTrials.gov Identifier: NCT04329507
• Recruitment Status: Completed
• First Posted: April 1, 2020
• Last Update Posted: September 8, 2021
• Sponsor: NHS Lothian
• Information provided by (Responsible Party): NHS Lothian

Study Description

Brief Summary:

On Dec 31, 2019, a number of viral pneumonia cases were reported in China. The virus causing pneumonia was then identified as a new coronavirus called SARS-CoV-2. Since this time, the infection called coronavirus disease 2019 (COVID-19) has spread around the world, causing huge stress for health care systems. To diagnose this infection, throat and nose swabs are taken. Unfortunately, the results often take more than 24 hrs to return from a laboratory. Speeding diagnosis up would be of great help.

This study aims to look at the breath to find signs that might allow clinicians to diagnose the coronavirus infection at the bedside, without needing to send samples to the laboratory. To do this, the team will be using a machine called a BreathSpec which has been adapted to fit in the hospital for this purpose.

Condition or disease	Intervention/treatment
COVID-19; Respiratory Disease	Diagnostic Test: Breath test

Detailed Description:

Analysis of volatile organic compounds (VOCs) in exhaled breath is of increasing interest in the diagnosis of lung infection. Over 2,000 VOCs can be detected through gas chromatography and mass spectrometry (GC-MS); patterns of VOC detected can offer information on chronic obstructive pulmonary disease, asthma, lung cancer and interstitial lung disease. Unfortunately, GC-MS while highly sensitive cannot be done at the bedside and at best takes hours to prepare samples, run the analysis and then interpret the results.

Compared with other methods of breath analysis, ion mobility spectrometry (IMS) offers a tenfold higher detection rate of VOCs. By coupling an ion mobility spectrometer with a GC column, GC-IMS offers immediate twofold separation of VOCs with visualisation in a three-dimensional chromatogram. The total analysis time is about 300 seconds and the equipment has been miniaturised to allow bedside analysis.

The BreathSpec machine has been previously used to study both radiation injury in patients undergoing radiotherapy at the Edinburgh Cancer Centre (REC ref 16-SS-0059, as part of the H2020 TOXI-triage project, http://www.toxi-triage.eu/) and pneumonia in patients presenting to the ED of the Royal Infirmary of Edinburgh (REC ref 18-LO-1029). This work has developed artificial intelligence methodology that allows rapid analysis of the vast amount of data collected from these breath samples to identify signatures that may indicate a particular pathological process such as pneumonia or radiation injury.

The TOXI-triage project showed that the BreathSpec GC-IMS could rapidly triage individuals to identify those who had been exposed to particular volatile liquids in a mass casualty situation (http://www.toxi-triage.eu/).

A pilot trial assessed chest infections at the Acute Medical Unit of the Royal Liverpool University Hospital. The final diagnostic model permitted fair discrimination between bacterial chest infections and chest infections due to other agents with an area under the receiver operator characteristic curve (AUC-ROC) of 0.73 (95% CI 0.61-0.86). The summary test characteristics were a sensitivity of 62% (95% CI 41-80%) and specificity of 80% (95% CI 64 - 91%) [8].

This was expanded in the EU H2020 funded "Breathspec Study" which aimed to differentiate breath samples from patients with bacterial or viral upper or lower respiratory tract infection. Over 1220 patients were recruited, with 191 patients identified as definitely bacterial infection and 671 classed as definitely not bacterial. Virology was undertaken on all patients, with 259 patients confirmed viral infection. Date processing is still on going to determine how well they can be distinguished using this methodology. More than 100 patients were recruited to this study in Edinburgh. Since then, artificial intelligence has been incorporated into our analytical processes, permitting faster and more refined analysis.

Our ambition is that this technology will identify a signature of Covid-19 pneumonia or within 10 min in non-invasively collected breath samples to allow triage of patients into high and low risk categories for Covid-19. This will allow targeting of scarce resources and complex protocols associated with high risk patients including personal protective equipment (PPE), cohorting, and dedicated medical and nursing personel.

A healthy volunteer arm was added in July 2020 - 40 particpants

Study Design

• Study Type: Observational
• Actual Enrollment: 225 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Non-invasive Detection of Pneumonia in Context of Covid-19 Using Gas Chromatography - Ion Mobility Spectrometry (GC-IMS)
• Actual Study Start Date: March 25, 2020
• Actual Primary Completion Date: January 31, 2021
• Actual Study Completion Date: May 30, 2021

Groups and Cohorts

Intervention Details:

• Diagnostic Test: Breath test
  collection of an exhaled breath sample

Outcome Measures

Primary Outcome Measures :

1. To perform a study in patients with clinical features of pneumonia/chest infection to identify a signature of Covid-19 pneumonia in patients exposed to SARS-CoV-2, compared to unexposed patients or those without. [ Time Frame: up to daily during hospital admission ]
   breath sample collection

Secondary Outcome Measures :

1. Detection of markers of Covid-19 pneumonia in non-invasive breath samples. [ Time Frame: multiple samples up to 60 days ]
   breath sample collection
2. Relationship of this biomarker signature to the presence of SARS-CoV-2 in nasal and throat swabs. [ Time Frame: multiple samples up to 60 days ]
   breath sample collection
3. Subsequently, the signature's relationship to other biomarkers of SARS-CoV-2 infection which are currently being explored [ Time Frame: multiple samples up to 60 days ]
   breath sample collection
4. In a smaller group of participants, ideally daily non-invasive breath samples will be collected to determine if there are changes between SARS-CoV-2 positive patients and those that are negative until hospital discharge or undue participant burden . [ Time Frame: multiple samples up to 60 days ]
   breath sample collection

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to hospital with respiratory signs and tested for SARS-CoV-2

Criteria

Inclusion Criteria:

• ≥18 years old with clinical features consistent with pneumonia or chest infection due to SARS-CoV-2 AND

  • presenting to the Royal Infirmary of Edinburgh where they are swabbed and triaged for Covid-19.

Exclusion Criteria:

• Inability to provide informed consent
• Age 17 years or less

Contacts and Locations

Locations

United Kingdom

NHS Lothian

Edinburgh, United Kingdom, EH16 4SA

Sponsors and Collaborators

NHS Lothian

More Information

• Responsible Party: NHS Lothian
• ClinicalTrials.gov Identifier: NCT04329507
• Other Study ID Numbers: 282014
• First Posted: April 1, 2020
• Last Update Posted: September 8, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: no plan made as yet - this research needs to be expedited during the pandemic

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NHS Lothian:

COVID-19

Additional relevant MeSH terms:

COVID-19; Pneumonia; Respiration Disorders; Respiratory Tract Diseases; Respiratory Tract Infections; Infections; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases