The outbreak of COVID-19 has created an unprecedent global crisis. While the polymerase
chain reaction (PCR) is the gold standard method for detecting active SARS-CoV-2
infection, alternative high-throughput diagnostic tests are of a significant value to
meet universal testing demands. Here, we describe a new design of the MasSpec Pen
technology integrated to electrospray ionization (ESI) for direct analysis of clinical
swabs and investigate its use for COVID-19 screening. The redesigned MasSpec Pen system
incorporates a disposable sampling device refined for uniform and efficient analysis of
swab tips via liquid extraction directly coupled to an ESI source. Using this system, we
analyzed nasopharyngeal swabs from 244 individuals including symptomatic COVID-19
positive, symptomatic negative, and asymptomatic negative individuals, enabling rapid
detection of rich lipid profiles. Two statistical classifiers were generated based on
the lipid information acquired. Classifier 1 was built to distinguish symptomatic
PCR-positive from asymptomatic PCR-negative individuals, yielding a cross-validation
accuracy of 83.5%, sensitivity of 76.6%, and specificity of 86.6%, and validation set
accuracy of 89.6%, sensitivity of 100%, and specificity of 85.3%. Classifier 2 was built
to distinguish symptomatic PCR-positive patients from negative individuals including
symptomatic PCR-negative patients with moderate to severe symptoms and asymptomatic
individuals, yielding a cross-validation accuracy of 78.4%, specificity of 77.21%, and
sensitivity of 81.8%. Collectively, this study suggests that the lipid profiles detected
directly from nasopharyngeal swabs using MasSpec Pen-ESI mass spectrometry (MS) allow
fast (under a minute) screening of the COVID-19 disease using minimal operating steps
and no specialized reagents, thus representing a promising alternative high-throughput
method for screening of COVID-19.