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

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.