In South Africa, COVID-19 Breath Test Trial Set for June

The investigators are waiting on approval from regulatory authorities to begin the test and work out the logistics of importing it into South Africa, as many tests suppliers have been affected by lockdown regulations. If all moves ahead, the scientists will use a sensitive, handheld device fitted with disposable nanosensors that pick up gases in a normal exhaled breath. For the Phase 1 study, breath samples will be collected from 60 adults with positively confirmed COVID-19 and 90 negative controls. Ezintsha is assessing the product and the developer, US-based Canary Health Technologies, would commercialize it. 

A cloud-based pattern-recognition technology will determine if a COVID-19 breath pattern can be established with accuracy. 

“This study at Wits will confirm the expected metabolic fingerprint of COVID-19 disease in the breath based on our assessment of the impact of COVID-19 on human body,” Raj Reddy, the chief executive officer of Canary and inventor of the technology, tells The Scientist.

SARS-CoV-2, the virus that causes COVID-19, can initiate oxidative stress by a similar mechanism observed in other viral pneumonias, according to Reddy, with the production of highly reactive nitrogen oxide species. “This would in turn enhance the concentration of alkanes and oxygenated compounds that are exhaled from the breath. A larger load of distinctive biomarker molecules would eventually result in higher sensor response for patients with COVID-19 disease as compared to COVID-19 negative individuals,” says Reddy. “Our differentially reactive sensor system is expected to generate a distinct pattern that can discriminate between people with COVID-19 disease and those without.”

One challenge the test may face is the reliance on an internet-based “lab in the cloud” for analysis, given that some regions in Africa have limited internet access.

Scientists will then use the breath patterns to measure the sensitivity and specificity of the test when compared to a standard PCR-based diagnostic.

Majam says he believes the test is very safe, as the disposable sensor prevents COVID-19 infected breath from touching the inside of the main device that is used to transmit the data to the cloud for analysis. The machine is disinfected between uses. 

“Any rapid test that could be used to identify infected individuals during this pandemic, especially those who are asymptomatic, is very important, says Burtram Fielding, a molecular biologist at the University of Western Cape who has been working on coronaviruses since 2003.

Diagnostic tests modeled around the same type of technology for asthma and lung disease are globally in use. The typical problems with these types of tests are that they are not very specific or sensitive, Fielding says. “This means that it could register false positives—someone tests positive, but is not infected—and false negatives—someone tests negative, but is indeed infected,” Fielding tells The Scientist. The latter, he says, is of much greater concern as an infected person could spread the disease not knowing that they are positive. False positives could also be due to the test detecting the same biomarkers for other, less-dangerous coronaviruses or other types of viruses altogether.

As with all other rapid tests, this could make a good screening tool if the sensitivity and specificity are high enough, Fielding says. Used as a screening test, individuals testing positive could at least be isolated while they are tested by the confirmatory RT-PCR test, which is the gold standard. “Unless the clinical trial shows a very high sensitivity and specificity, this would not be a very useful test during the epidemic of a virus with such a high infective rate,” he says.

Johanna Lindahl, a veterinary epidemiologist for the International Livestock Research Institute and the Swedish University of Agricultural Sciences, agrees it’s an interesting method, and echoes Fielding’s sentiments, “Other viruses may also produce similar changes in the breath, and therefore could give false positive results, unless this is really evaluated,” she tells The Scientist. 

“I think it is in the very early stages to talk about whether it will actually work, its specificity, and its sensitivity,” Ahmed Kalebi, the group managing director for Lancet Group of Laboratories for East Africa, based in Nairobi, Kenya, tells The Scientist. If the breath test’s accuracy is borne out through the clinical trial, the advantage of this approach is obvious in terms of speed and point-of-care accessibility compared to lab tests, Kalebi adds.

Gerald Mboowa, a bioinformatics scientist at the Infectious Diseases Institute at Makerere University in Uganda, says COVID-19 testing kits in his country mainly imported from Europe and the United States are in short supply. “In Uganda, the total number of COVID-19 positive stands at 241 [as of May 28] and over 108 cross-border truck drivers have tested positive for COVID-19,” he says. Rapid testing in a landlocked country such as Uganda can offer quick decisions, for instance, regarding which truck drivers at the border need quarantining before they can be granted entry.

“I am optimistic that this product will meet its expectations,” says Mboowa. One challenge the test may face is the reliance on an internet-based “lab in the cloud” for analysis, given that some regions in Africa have limited internet access, Mboowa tells The Scientist.

In May, researchers at Ben-Gurion University of the Negev in Israel announced they had developed a COVID-19 electro-optical test of nose, throat, or breath samples that looks for signs of the virus’s presence itself and gives results in less than one minute. This product would cost approximately $50 US. Current PCR tests range between $45 and $70 US. “We believe we will be able to produce the tests at a significantly lower cost,” says Majam. 

Canary Health is discussing plans to conduct clinical trials on the device in the United Kingdom and the US, but a trial planned in Hong Kong won’t go ahead now that there are very few COVID-19 cases, according to Anna Wang, Canary’s senior vice president for corporate affairs.

“We will seek accelerated regulatory approval in South Africa as soon as they are confident of the performance, [and we hope] to have this test on the market before the end of 2020,” Wang says.