Rising population density and global mobility are among the reasons why pathogens such as SARS-CoV-2, the virus that causes COVID-19, spread so rapidly across the globe. The policy response to such pandemics will always have to include accurate monitoring of the spread, as this provides one of the few alternatives to total lockdown. However, COVID-19 diagnosis is currently performed almost exclusively by reverse transcription polymerase chain reaction (RT-PCR). Although this is efficient, automatable, and acceptably cheap, reliance on one type of technology comes with serious caveats, as illustrated by recurring reagent and test shortages. We therefore developed an alternative diagnostic test that detects proteolytically digested SARS-CoV-2 proteins using mass spectrometry (MS). We established the Cov-MS consortium, consisting of 15 academic laboratories and several industrial partners to increase applicability, accessibility, sensitivity, and robustness of this kind of SARS-CoV-2 detection. This, in turn, gave rise to the Cov-MS Digital Incubator that allows other laboratories to join the effort, navigate, and share their optimizations and translate the assay into their clinic. As this test relies on viral proteins instead of RNA, it provides an orthogonal and complementary approach to RT-PCR using other reagents that are relatively inexpensive and widely available, as well as orthogonally skilled personnel and different instruments. Data are available via ProteomeXchange with identifier PXD022550.

The mobile phase additive (DMSO) has been described as a useful tool to enhance electrospray ionization (ESI) of peptides and proteins. So far, this technique has mainly been used in proteomic/peptide research, and its applicability in a routine clinical laboratory setting (i.e., doping control analysis) has not been described yet. This work provides a simple, easy to implement screening method for the detection of doping relevant small peptides (GHRPs, GnRHs, GHS, and vasopressin-analogues) with molecular weight less than 2 kDa applying DMSO in the mobile phase. The gain in sensitivity was sufficient to inject the urine samples after a 2-fold dilution step omitting a time consuming sample preparation. The employed analytical procedure was validated for the qualitative determination of 36 compounds, including 13 metabolites. The detection limits (LODs) ranged between 50 and 1000 pg/mL and were compliant with the 2 ng/mL minimum detection level required by the World Anti-Doping Agency (WADA) for all the target peptides. To demonstrate the feasibility of the work, urine samples obtained from patients who have been treated with desmopressin or leuprolide and urine samples that have been declared as adverse analytical findings were analyzed. Graphical Abstract ᅟ.

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Rising population density and global mobility are among the reasons why pathogens such as SARS-CoV-2, the virus that causes COVID-19, spread so rapidly across the globe. The policy response to such pandemics will always have to include accurate monitoring of the spread, as this provides one of the few alternatives to total lockdown. However, COVID-19 diagnosis is currently performed almost exclusively by Reverse Transcription Polymerase Chain Reaction (RT-PCR). Although this is efficient, automatable and acceptably cheap, reliance on one type of technology comes with serious caveats, as illustrated by recurring reagent and test shortages. We therefore developed an alternative diagnostic test that detects proteolytically digested SARS-CoV-2 proteins using Mass Spectrometry (MS). We established the Cov-MS consortium, consisting of fifteen academic labs and several industrial partners to increase applicability, accessibility, sensitivity and robustness of this kind of SARS-CoV-2 detection. This in turn gave rise to the Cov-MS Digital Incubator that allows other labs to join the effort, navigate and share their optimizations, and translate the assay into their clinic. As this test relies on viral proteins instead of RNA, it provides an orthogonal and complementary approach to RT-PCR, using other reagents that are relatively inexpensive and widely available, as well as orthogonally skilled personnel and different instruments. Data are available via ProteomeXchange with identifier PXD022550.

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