covidProgress is impossible without change, and those who cannot change their minds cannot change anything” – George Bernard Shaw

“The new normal,” “social distancing,” “flattening the curve” – in any other year, day or night – these phrases would not have meant much. However, this is 2020 and these phrases do mean a lot more than we ever expected! COVID-19 is a real issue, a big threat – perhaps much bigger than most other pandemics/epidemics known to us. From detection and monitoring of a potentially infected patient to ensuring the status of a ‘cured’ patient who was diagnosed as COVID-19 positive, — the analytical process relies heavily on the strength of the technology. Real-Time-Polymerase Chain Reaction is the most trusted in that list of analytical technology and is widely used by most around the world in routine monitoring of patients who are either asymptomatic, showing symptoms, or have been diagnosed as infected with COVID-19.

There are several ways to test for COVID-19 – from studying viral antigens, nucleic acids or detection of virus-specific antibodies in the blood samples collected from patients. Each of these testing approaches has their preferred analytical technology. As an example, historical viral antigen testing tends to be primarily based on immunoassays, which can offer good detection sensitivity and rapid turnaround times. However, RT-PCR has become the preferred path for COVID-19 detection as this technology exhibits significantly higher sensitivity (compared to immunoassays). RT-PCR can also address viruses that exhibit antigenic shifts. With the turnaround times of RT-PCR being similar to Immunoassays, this technology has become the most popular technology choice for COVID-19 identification. Alternate approaches that exhibit equal or better selectivity, stability, and throughput while achieving similar sensitivity can help, too.

One of the recent publications from Dr. Akhilesh Pandey (Mayo Clinic, Rochester, MN) in MedRxiv highlights a unique workflow approach capitalizing Thermo Fisher’s  Thermo Scientific™ Orbitrap™ Exploris 480 high-resolution accurate mass spectrometer (HRAM), high field asymmetric waveform ion mobility spectrometry (FAIMS), Mass Spectrometric Immunoassay (MISA) columns to detect SARS-CoV-2 from clinical samples. The research paper studied 363 nasopharyngeal residual swab samples from patients with matched clinical molecular test results using RT-PCR and samples were prepared using Thermo ScientificTM. Dr. Pandey’s studies comprised LC-MS analysis of inactivated SARS-CoV-2 virus and recombinant viral proteins in determination, selection of critical proteins and peptides. Upon selection, the optimal peptides were used to develop a targeted parallel reaction monitoring (PRM) assay to characterize and quantify the targeted peptides. The group continued to develop targeted assays via automated antibody capture using Thermo Scientific™ MSIA™ (Mass Spectrometric Immunoassay) microcolumns. Dr. Pandey’s group also used Thermo Scientific™ FAIMS Pro™ interface (capitalizing the high field asymmetric waveform ion mobility spectrometry) to further improve the sensitivity of detection in the PRM workflow. The evaluation of the nasopharyngeal swab samples with and without FAIMS showed significantly higher signal-to-noise (S/N) ratio for the selected peptides using FAIMS. Several such examples with peptides from nasopharyngeal swab samples containing high viral load were reported in this article.

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Dr. Pandey’s results and similar efforts across the globe do not necessarily pose LC-MS as a competing or better technology than RT-PCR. So how does LC-MS fit into the COVID-19 testing paradigm? LC-MS is an excellent orthogonal, complementary technology that can be used to reduce the overall testing volume pressure on RT-PCR. In addition, as indicated by Dr Pandey’s work, LC-MS demonstrates the highest specificity with the ability to achieve similar sensitivity. Measurement of the protein-peptide markers is also shown to be a more stable assay, that does require additional storage precautions. LC-MS a desirable technology to address some critical analytical requirements, especially when it comes to something as deadly and threatening as COVID-19.

Transitioning to LC-MS can be challenging” –I hear this way too often along with the challenges being i) lack of expertise; ii) time to develop methods; iii) cost/sample and availability of capital funds needed to purchase LC-MS, etc. However, now is the time for us to be prepared to address one of the most critical challenges – saving human lives. LC-HRAM (MS) can enable increased confidence in data, which in turn offers better information resulting in better detection, diagnosis, prevention/cure of critical disease states.

For Clinical Research Only – Not for Use in Diagnostic Procedures.