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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Seasonal factitious increase in serum potassium: still a problem and should be recognised.

AIM: Spurious serum elevation of potassium concentration can occur in the presence of cold ambient temperatures and the aim of this study was to assess the effect of changes in temperature on the average serum potassium concentration in our population. METHOD: We conducted a retrospective review of all serum potassium samples received to the laboratory between January 2009 and September 2012 from accident & emergency (AE), general practice (GP), in-patient (IP) and out-patient (OP) departments and compared these with the mean ambient temperatures for these months supplied by the Met Office for South East and Central England. RESULTS: We have identified that in a relatively condensed south London region seasonal factitious serum potassium elevation occurs in primary care samples but also somewhat surprisingly also in hospital in-patient and out-patient samples although apparently less so in AE samples. We found an inverse correlation between ambient temperature and serum potassium in GP blood samples (Pearson correlation coefficient=-0.83, P<0.001), there were weaker correlations with inpatient (-0.41, P=0.005) and outpatient samples (-0.28, P=0.06) but not in AE samples. CONCLUSION: Factitious seasonal potassium increase can occur in patient blood samples particularly those from primary health care.