Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis

Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis

Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-aff...

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Bibliographic Details
Main Authors: Andreas Hober, Khue Hua Tran-Minh, Dominic Foley, Thomas McDonald, Johannes PC Vissers, Rebecca Pattison, Samantha Ferries, Sigurd Hermansson, Ingvar Betner, Mathias Uhlén, Morteza Razavi, Richard Yip, Matthew E Pope, Terry W Pearson, Leigh N Andersson, Amy Bartlett, Lisa Calton, Jessica J Alm, Lars Engstrand, Fredrik Edfors
Format: article
Language:EN
Published: eLife Sciences Publications Ltd 2021
Subjects:
SARS CoV-2
COVID-19
SISCAPA
proteomics
diagnostics
mass spectrometry
Medicine
R
Science
Q
Biology (General)
QH301-705.5
Online Access:https://doaj.org/article/b86beb7f359342dfa0a6a2b4f3d48930
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Summary:Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity 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 phosphate-buffered saline (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 correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). 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.

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