Rapid and Sensitive Detection of SARS-CoV-2 Infection Using Quantitative Peptide Enrichment Analysis

Reliable, robust, large-scale molecular testing for SARS-CoV-2 is essential for monitoring the ongoing Covid-19 pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immunoaffinity enrichment combined with liquid chromatography - mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in PBS swab media from combined throat/nasopharynx/saliva samples.
The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their corresponding RT-PCR readout. The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with quantitative readout of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 20 to 35. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% specificity and 86% sensitivity when analyzing clinical samples collected from asymptomatic patients. These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.