Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use.

Humans SARS-CoV-2 Pandemics COVID-19 / diagnosis COVID-19 Testing Tandem Mass Spectrometry / methods Chromatography, Liquid Prospective Studies Clinical Laboratory Techniques / methods Sensitivity and Specificity Peptides

high performance liquid chromatography laboratory methods & tools mass spectrometry proteins

Journal

Clinical chemistry and laboratory medicine

ISSN: 1437-4331

Titre abrégé: Clin Chem Lab Med

Pays: Germany

ID NLM: 9806306

Informations de publication

Date de publication:
27 01 2023

Historique:

received: 05 10 2022

accepted: 04 11 2022

pubmed: 18 11 2022

medline: 16 12 2022

entrez: 17 11 2022

Statut: epublish

Résumé

During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95. This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.

Identifiants

DOI: 10.1515/cclm-2022-1000 PMID: 36395058

pubmed: 36395058

pii: cclm-2022-1000

doi: 10.1515/cclm-2022-1000

doi:

Substances chimiques

Peptides 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

302-310

Subventions

Organisme : Medical Research Council

ID : MC_PC_18054

Pays : United Kingdom

Informations de copyright

Références

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