  Rapid testing is essential to fighting pandemics such as COVID-19, the
disease caused by the SARS-CoV-2 virus. Exhaled human breath contains multiple
volatile molecules providing powerful potential for non-invasive diagnosis of
diverse medical conditions. We investigated breath detection of SARS-CoV-2
infection using cavity-enhanced direct frequency comb spectroscopy (CE-DFCS), a
state-of-the-art laser spectroscopic technique capable of a real-time massive
collection of broadband molecular absorption features at ro-vibrational quantum
state resolution and at parts-per-trillion volume detection sensitivity. Using
a total of 170 individual breath samples (83 positive and 87 negative with
SARS-CoV-2 based on Reverse Transcription Polymerase Chain Reaction tests), we
report excellent discrimination capability for SARS-CoV-2 infection with an
area under the Receiver-Operating-Characteristics curve of 0.849(4). Our
results support the development of CE-DFCS as an alternative, rapid,
non-invasive test for COVID-19 and highlight its remarkable potential for
optical diagnoses of diverse biological conditions and disease states.
