Resolving omicron sub-variants of SARS CoV-2 coronavirus with MALDI mass spectrometry.

Mass mapping using high resolution mass spectrometry has been applied to identify and rapidly distinguish the omicron sub-variants across the BA.1-BA.5 lineages. Lineage-specific protein mutations in the surface spike protein give rise to peptide biomarkers of unique mass that can be confidently and sensitively detected with high resolution mass spectrometry. Those that are most efficiently ionised and detected within the S1 subunit in recombinant forms facilitate their detection in clinical specimens containing other SARS-CoV2 viral proteins and contaminants. A study of five dozen omicron-positive specimens, using a selected ion monitoring approach, detected peptide biomarkers for strains of BA.1, BA.2.75 and BA.4 sub-variants in 23%, 42% and 28% of samples respectively, consistent with their reported levels in the local population. The virus was confidently assigned in over 93% of omicron positive specimens. The ease of detection of the BA.2.75 variant, in particular, is of vital importance given its rapid global spread in late 2022 due to several immune evasive mutations within the receptor-binding domain.