Detection of SARS-CoV-2 infection by exhaled breath spectral analysis: Introducing a ready-to-use point-of-care mass screening method

Izhar Ben Shlomo, Hilel Frankenthal, Arie Laor, Ayala Kobo Greenhut

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background: The current SARS-CoV-2 pandemic created an urgent need for rapid, infection screening applied to large numbers of asymptomatic individuals. To date, nasal/throat swab polymerase chain reaction (PCR) is considered the “gold standard”. However, this is inconducive to mass, point-of-care (POC) testing due to person discomfort during sampling and a prolonged result turnaround. Breath testing for disease specific organic compounds potentially offers a practical, rapid, non-invasive, POC solution. The study compares the Breath of Health, Ltd. (BOH) breath analysis system to PCR's ability to screen asymptomatic individuals for SARS-CoV-2 infection. The BOH system is mobile and combines Fourier-transform infrared (FTIR) spectroscopy with artificial intelligence (AI) to generate results within 2 min and 15 s. In contrast to prior SARS-CoV-2 breath analysis research, this study focuses on diagnosing SARS-CoV-2 via disease specific spectrometric profiles rather than through identifying the disease specific molecules. Methods: Asymptomatic emergency room patients with suspected SARS-CoV-2 exposure in two leading Israeli hospitals were selected between February through April 2021. All were tested via nasal/throat-swab PCR and BOH breath analysis. In total, 297 patients were sampled (mean age 57·08 ± SD 18·86, 156 males, 139 females, 2 unknowns). Of these, 96 were PCR-positive (44 males, 50 females, 2 unknowns), 201 were PCR-negative (112 males, 89 females). One hundred samples were used for AI identification of SARS-CoV-2 distinguishing spectroscopic wave-number patterns and diagnostic algorithm creation. Algorithm validation was tested in 100 proof-of-concept samples (34 PCR-positive, 66 PCR-negative) by comparing PCR with AI algorithm-based breath-test results determined by a blinded medical expert. One hundred additional samples (12 true PCR-positive, 85 true PCR-negative, 3 confounder false PCR-positive [not included in the 297 total samples]) were evaluated by two blinded medical experts for further algorithm validation and inter-expert correlation. Findings: The BOH system identified three distinguishing wave numbers for SARS-CoV-2 infection. In the first phase, the single expert identified the first 100 samples correctly, yielding a 1:1 FTIR/AI:PCR correlation. The two-expert second-phase also yielded 1:1 FTIR/AI:PCR correlation for 97 non-confounders and null correlation for the 3 confounders. Inter-expert correlation was 1:1 for all results. In total, the FTIR/AI algorithm demonstrated 100% sensitivity and specificity for SARS-CoV-2 detection when compared with PCR. Interpretation: The SARS-CoV-2 method of breath analysis via FTIR with AI-based algorithm demonstrated high PCR correlation in screening for asymptomatic individuals. This is the first practical, rapid, POC breath analysis solution with such high PCR correlation in asymptomatic individuals. Further validation is required with a larger sample size. Funding: Breath of Health Ltd, Rehovot, Israel provided study funding.

Original languageEnglish
Article number101308
StatePublished - Mar 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)


Ayala Kobo Greenhut, PhD provided regulatory oversight, analyzed results, authored, and edited article text., Breath of Health Ltd, Rehovot, Israel provided study funding. The authors would like to thank the hospital administrations, emergency room, and laboratory staff of Hadassah Ein Karem Hospital, Jerusalem, Israel, and Sheba Tel-HaShomer Hospital, Ramat Gan, Israel, for their cooperation and assistance in conducting this study.

FundersFunder number
Sheba Tel-HaShomer Hospital


    • Detection
    • Exhaled breath spectral analysis
    • SARS-CoV-2
    • Screening method


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