Breath samples may help diagnose COVID-19 better: Study

Breath samples of patients may come in handy for a much accurate diagnosis of COVID-19 including that of its variants, and of non-COVID illnesses, a new study has suggested.

Investigators from the University of Michigan’s Max Harry Weil Institute for Critical Care Research and Innovation, US, used portable gas chromatography (GC) to examine breath samples collected during the surge of the Delta variant of the virus and its transition to Omicron, between April 2021 and May 2022, the study said.

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The results showed that the GC technology could diagnose COVID-19 with a high level of accuracy.

The study found that the volatile organic compounds contained in the breath of patients with Omicron differed from those in patients with Delta and earlier variants.

These molecular-level differences, according to the team, could potentially be used to distinguish between COVID-19, its variants and non-COVID illnesses.

The emergence of new COVID-19 variants has led to reduced accuracy across current rapid testing methods, the study said.

The results are published in the Journal of the American Medical Association (JAMA) Network Open.

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“Exhaled breath contains hundreds of VOCs, which the body produces in response to infection and inflammation,” said principal investigator and study author Xudong (Sherman) Fan, associate director of the Weil Institute.

“Early in the pandemic, we used GC technology to discover and define sets of variants of concern (VOCs) for detecting COVID-19. However, we needed to gain a better understanding of how dynamically emerging variants impact this technology,” Fan added.

Three cohorts

The team of researchers conducted a diagnostic study of 167 adult patients in the Michigan Medicine ICUs and emergency department.

They collected 205 breath samples from symptomatic and asymptomatic patients in three cohorts:

1. COVID-19 (2021): Patients with COVID-19 who were recruited before December 14, 2021 and were assumed to be infected by the Delta or earlier variants.

2. COVID-19 (2022): Patients with COVID-19 who were recruited from January 2022 to the end of May 2022 and were assumed to be infected by the Omicron variant.

3. Non-COVID-19 illness: Patients who were COVID-19 negative at the time of breath analysis, as well as patients who were previously COVID-19 positive but had recovered.

Using a novel point-of-care GC device developed by Fan and the team, in combination with an advanced biomarker discovery algorithm and data analysis platform developed at the university, the investigators defined four sets of VOCs that they were able to distinguish between COVID-19 (2021) and non-COVID illness.

They were able to differentiate these VOCs between COVID-19 and non-COVID illnesses with a sensitivity of 92.7 per cent, a specificity of 95.5 per cent and an accuracy of 94.7 per cent, the study said.

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However, when the team applied the same VOCs in a setting of presumed Omicron, sensitivity decreased drastically to 60.4 per cent, they said.

“We already knew clinically that different strains of SARS-CoV-2 can act quite differently,” said study co-author Robert Dickson, deputy director of the Weil Institute.

“This decrease in performance supports our suspicion that their effects on lung biology are quite different as well,” said Dickson.

Based on their findings, the team hypothesised that it could be possible to use breath analysis to distinguish between COVID variants.

They undertook additional biomarker searches and defined new VOCs to discern between Omicron and Delta, Omicron and non-COVID illness, and between patients with COVID-19 and non-COVID illness regardless of variants, they said.

The combined analysis resulted in the ability to detect COVID-19 infected patients, regardless of variant, from non-COVID patients with a sensitivity of 89.4 per cent, a specificity of 91 per cent and an accuracy of 90.2 per cent, the study said.

Close to RT-PCR, better than rapid antigen tests

The study said that the performance is close to that of RT-PCR tests, the gold standard, and better than many rapid antigen tests.

“This work suggests that breath analysis using point-of-care GC may be a promising method for detecting COVID-19 and similar diseases that result in VOC production,” said co-author and co-principal investigator Kevin Ward, executive director of the Weil Institute.