Comparative proteomics of human naso-oropharyngeal swabs from COVID19 patients for identification of potential biomarker candidates

COVID19 continues to be a public health issue with subvariants of the main strains causing infections globally. This study looks to identify potential biomarker candidates that can help to understand molecular etio-pathogenesis. Proteins from naso-oropharyngeal samples of healthy Control and COVID19 subjects were trypsin digested and subjected to liquid chromatography assisted mass spectrometry analysis on Orbitrap Fusion Lumos (ThermoFisher). Proteomic analysis was carried out using Proteome Discoverer 2.4 (ThermoFisher) using human and SARS-CoV-2 FASTA databases from UniProtKB. Proteins with fold Change ≤0.5, or ≥2 were designated as differentially expressed and taken up for interactomic analysis using STRING and Cytoscape, and pathway analysis using KEGG, Reactome, and Wiki pathway. Area under curve for receiver operating characteristic was done in MetaboAnalyst (v6.0) to estimate diagnostic parameters of sensitivity and specificity. Proteomic analysis of naso-oropharyngeal swabs from COVID19 patients identified 26 differentially expressed human proteins of which 11 are potential biomarker candidate proteins. In addition, 29 SARS-CoV-2 specific peptides from spike protein, nucleocapsid, membrane, ORF1ab, ORF6, ORF7a, ORF8 and ORF9b proteins have been identified of which 6 were mutated. These SARS-CoV-2 proteins make an array of interactions with the identified human proteins establishing their roles in pathogenesis of viral infection. Human biomarker candidate proteins are associated with alterations in glycolytic pathways and immune dysregulation, which are known to facilitate viral invasion, replication, and contribute to disease severity. Identified biomarker candidates have a minimum of 70% and a maximum of 100%, sensitivity and specificity thereby having translational value in developing protein-based tests that can complement currently available diagnostics for COVID19.