摘要:SummaryThe altered molecular proteins and pathways in response to COVID-19 infection are still unclear. Here, we performed a comprehensive proteomics-based investigation of nasopharyngeal swab samples from patients with COVID-19 to study the host response by employing simple extraction strategies. Few of the host proteins such as interleukin-6, L-lactate dehydrogenase, C-reactive protein, Ferritin, and aspartate aminotransferase were found to be upregulated only in COVID-19-positive patients using targeted multiple reaction monitoring studies. The most important pathways identified by enrichment analysis were neutrophil degranulation, interleukin-12 signaling pathways, and mRNA translation of proteins thus providing the detailed investigation of host response in COVID-19 infection. Thus, we conclude that mass spectrometry-detected host proteins have a potential for disease severity progression; however, suitable validation strategies should be deployed for the clinical translation. Furthermore, thein silicodocking of potential drugs with host proteins involved in the interleukin-12 signaling pathway might aid in COVID-19 therapeutic interventions.Graphical abstractDisplay OmittedHighlights•High-resolution mass spectrometry of swab identified 164 significant host proteins•Upregulation of LDH, Ferritin, and AST was validated by MRM assays•Significant alteration of immune response and translational pathways was observed•In silicodocking identified Loratadine binding to interleukin signaling proteinsSpecimen; molecular biology; proteomics