A Covid breathalyzer

One of the successes of the Covid-19 pandemic response has been the development of a wide variety of diagnostic tests to detect coronavirus infection. The gold standard based on accuracy is the PCR test, in which the viral RNA genome (from a nasal swab) is detected by reverse transcription (RT) to DNA followed by PCR amplification. However laboratory equipment (i.e. PCR machine) is needed, and so one cannot perform the test at home. Fortunately, antigen tests have also been developed that detect viral proteins using antibodies attached to lateral flow strips. They are simple to perform (nasal swab into a solution that is spotted on the strip) taking about 10 minutes, and are approximately 80% accurate. But the 10 minutes and swabbing the nose can be a barrier for those desiring an even more rapid (i.e. real-time) and streamlined testing.

The dream is inventing a breath test in which a few breaths into a device could register the presence (or absence) of coronavirus. Such real-time monitoring could be used to screen visitors and employees to a hospital, for example. If sufficiently accurate, the breath test could identify people with a coronavirus infection quickly and effortlessly.

Progress is being made toward this goal. Interestingly, the current generation of experimental Covid breath tests do not try to detect the virus directly. Instead, they monitor the presence of volatile chemicals in the breath that are correlated with a coronavirus infection. In principle, this approach is similar to a dog sniffing out a person with Covid (QH).

There are several companies pursuing this objective, and one of the furthest advanced is the company InspectIR (FierceBiotech):

“A portable breathalyzer developed by InspectIR Systems aims to deliver a result within three minutes by looking for the exhaled chemical compounds that can come with an infection.”

How does the InspectIR COVID-19 Breathalyzer work?

“The device includes its own miniaturized mass spectrometer, shrunk down to about the size of a carry-on suitcase. It’s designed to be used under the supervision of a healthcare professional in locations such as doctors' offices, hospitals and mobile testing sites.

By blowing into a tube connected directly to the machine, InspectIR’s test searches for five specific volatile organic compounds that are produced by the body when it’s fighting off COVID.” 

Basically a person blows into a tube connected to a mass spectrometer that analyzes the breath sample for five volatile organic compounds (Figure 1). The whole test takes three minutes (which is shorter than the 10-15 minutes of an antigen test). 

Of course the big question is how accurate is the breathalyzer? According to the article, accuracy was assessed in a study (pre-Omicron) of more than 2,400 people with and without symptoms, and 4.2% of participants testing positive by PCR. The false negative rate by the breath test was less than 1%, corresponding to a sensitivity (true positive rate = percent of true positives identified by test) of over 99%, which is impressive, suggesting that nearly everyone with Covid was detected. The false positive rate was not mentioned. The accuracy results were confirmed by further testing when the Omicron variant was dominant. Based on these data, the company was granted an emergency authorization (EUA) by the FDA, a significant stamp of approval.

The accuracy appears to be quite good (assuming the false positive rate is low), and as a breath test, the device is the first of its kind for Covid approved by the FDA. The downsides are that it is not quite real-time (3 min), and requires an expensive instrument (mass spec). Also, there is the question (related to the issue of false positives) of whether the breathalyzer can distinguish between various types of viral infections (i.e. Covid versus flu or RSV); it is possible that volatile chemical signature detected by the breathalyzer is indicative of an immune response to a viral pathogen without being specific to coronavirus. Regardless, the InspectIR breathalyzer draws a line in the sand for future breath tests to match or exceed in accuracy, speed, and convenience/cost. 

I previously wrote about a fanciful experimental prototype that won the open innovation track of the 2021 X-Prize competition to develop high-quality, affordable COVID-19 testing. The device used a novel technology (RNA aptamers), and the company claimed it can detect the virus within 30 seconds with 99% accuracy "for the price of a latte ($5)." However, without an authorization by the FDA there is no validation of these claims, and so the device remains as vaporware.

Figure 1. The new InspectIR COVID-19 Breathalyzer measures the concentrations of five organic volatile compounds in your breath to determine whether or not you have been infected by coronavirus.