Rapid Screening of COVID-19 Disease Directly from Clinical Nasopharyngeal Swabs using the MasSpec Pen Technology

Abstract

The outbreak of COVID-19 has created an unprecedent global crisis. While PCR is the gold standard method for detecting active SARS-CoV-2 infection, alternative high-throughput diagnostic tests are of 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 a 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 aquired. Classifier 1 was built to distinguish symptomatic PCR-positive from asymptomatic PCR-negative individuals, yielding 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% accuracy, 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 MS allows fast (under a minute) screening of COVID-19 disease using minimal operating steps and no specialized reagents, thus representing a promising alternative high-throughput method for screening of COVID-19.

Advances in rapid detection of SARS-CoV-2 by mass spectrometry

“…Apart from the above, some innovative handheld devices were also developed for mass spectrometric analysis in clinics. For example, a handheld device modified based on the MasSpec Pen technology [ 61 ] integrated with ESI-MS was recently reported to successfully analyze lipid profiles in nasopharynx swabs [ 62 ]. It was demonstrated that the lipid profiles could allow identification of SARS-CoV-2 infected patients, as changing in lipid profiles was found upon SARS-CoV-2 infection [ 63 , 64 ].…”

“…The solvent is transported from conduit 1 to extract lipids from the swab for 10 s. The lipid-extracted solvent is delivered to the ESI-MS for data acquisition through conduit 2 for 30 s. The total analysis takes about 45 s only (Adapted from Ref. [ 62 ]). …”