Breathalyzer Testing: The Future of COVID-19 Diagnostics or Just Hot Air?

Perhaps the biggest story in COVID-19 diagnostics in 2021 has been the emergence of rapid, point-of-care and at-home tests for use in screening asymptomatic populations as the engine of growth. While test producers, policy makers and community health officials will continue to prioritize these tests in the months ahead, the modality of rapid COVID-19 testing is already beginning to evolve. Next year at this time, we may conclude that 2022 was the year that COVID-19 testing advanced beyond swabs to breathalyzers.

The Rapid Testing Challenge

Most of the current rapid assays on the market rely on antigen secreted by antibodies the body produces to fight SARS-CoV-2 to detect the virus. Serology tests detect SARS-CoV-2 antibodies directly. While suitable for screening purposes, antibody and antigen testing is relatively lacking in sensitivity and accuracy. The label “rapid” also belies the fact that these tests do take minutes to process and do not deliver results immediately the way tests based on other modalities do.

Since the public health emergency began, test makers and researchers have sought to develop tests based on other kinds of biomarkers. Among the most promising biomarkers are volatile organic compounds (VOCs) expelled by the lungs that can be detected via a rapid breath test, similar to breathalyzer testing used by law enforcement to measure blood alcohol content to detect impairment. In addition to offering greater accuracy and speed, breathalyzer tests are less invasive than current SARS-CoV-2 rapid tests that rely on samples collected by swabs.

Is COVID-19 Breathalyzer Testing Just a Lot of Hot Air? 

It sounds like a good idea. But will it actually work? There are grounds for skepticism. After all, there is still no reliable exhaled breath test for lung cancer even though researchers have been working on the concept for decades.

Screening real-world populations for coronavirus using breathalyzer testing has actually been tried. In February 2021, the Netherlands government rolled out a screening experiment using a rapid breath test device. The SpiroNose contains seven metal oxide semiconductor sensors that detect thousands of VOCs in exhaled air; when someone has a COVID-19 infection, the mix changes. The experiment was tried in Amsterdam. People with negative test results got the all-clear. Those who tested positive or returned an inconclusive result then had to undergo antigen or polymerase chain reaction (PCR) testing.

But, alas, the experiment proved less than successful and the government had to close it down when 25 people who tested negative on the device turned out to have COVID-19 after all. However, the government concluded that SpiroNose was not the problem and left its authorization intact. It is now being used by a commercial testing company for screening attendees of large public events.

New Study Validates Breathalyzer Technology for SARS-CoV-2

A more positive development is the increasing number of studies that have appeared supporting the feasibility of using VOCs-based breathalyzer testing to detect coronavirus. That includes an exciting new clinical validation study published in the online journal Plos One on October 28.

Researchers from Ohio State administered a breathalyzer test that uses nanosensors to detect specific VOCs in the breath of 46 patients admitted to the ICU. They examined data from patients admitted to the ICU for acute respiratory failure who required mechanical ventilation. All patients were tested for COVID-19 before admission. Twenty-three of them had COVID-19 infection and 23 of them did not. Patients breathed into a “breath bag” on days 1, 3, 7, and 10 of their ICU stay (or until the patient was removed from their ventilator).

The test detected COVID-19 with 88 percent sensitivity, as compared to the 71 percent to 98 percent sensitivity range associated with current SARS-CoV-2 PCR detection platforms. The study authors also found that the breathalyzer test had:

• A specificity of 83 percent;
• A positive predictive value of 78 percent;
• A negative predictive value of 90 percent; and
• Accuracy of 85 percent.

The authors concluded that the test detects a “breath print” unique to COVID-19 based on amounts of oxygen, ammonia, and nitric oxide. “This noninvasive breath test technology can pick up early COVID-19 infection within 72 hours of the onset of respiratory failure, allowing us to rapidly screen patients in a single step and exclude those without COVID-19 on mechanical ventilation,” noted study co-author Matthew Exline, MD, of the Ohio State University.

“This is the first study to demonstrate the use of a nanosensor breathalyzer system to detect a viral infection from exhaled breath prints,” according to co-author Pelagia-Irene Gouma, MD, also of Ohio State.

The authors added that traditional molecular testing for COVID has “low detection accuracy” for early disease, and “persistent positive results after an infection has resolved.” They plan to seek Emergency Use Authorization (EUA) for their device from the U.S. Food and Drug Administration (FDA).

Other COVID-19 Breathalyzer Tests in the Works

The Ohio State study is just one of many research projects evaluating whether breathalyzer nanosensor technology based on VOCs can be applied to COVID-19 detection. Projects are also underway at the University of Colorado, Rutgers University and the University of North Texas. Meanwhile, diagnostics companies have been making progress in creating commercial coronavirus breathalyzer tests for widespread use in asymptomatic screening. Notable examples:

• The National Aeronautics and Space Administration (NASA) is testing a prototype of a COVID-19 breathalyzer device called E-Nose originally developed by Tennessee subcontractor Variable Inc. to measure air quality inside a spacecraft (See, Diagnostic Testing and Emerging Technology, May 22, 2021);
• Canary Health Technologies and Divoc Laboratories are collaborating to develop and validate a handheld digital breath test called ASU Detect CV19, which uses cloud-based artificial intelligence technology to detect the SARS-CoV-2 virus in less than three minutes (See, Laboratory Industry Report, February 22, 2021);
• Singapore startup Silver Factory Technology has begun testing a SARS-CoV-2 breathalyzer at Singapore Changi Airport and plans to build a facility to mass produce the device; and
• Breathonix, another Singapore firm, which was spun off from the National University of Singapore, began testing its own SARS-CoV-2 breath test at a busy bridge checkpoint in Malaysia that is used to test hundreds of incoming truck drivers a day.

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This article originally appeared in G2 Intelligence, Diagnostic Testing & Emerging Technologies, January 2022.