Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients

Abstract

COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative nasooropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.

Increased elastase sensitivity and decreased intramolecular interactions in the more transmissible SARS-CoV-2 variants’ spike protein: Analysis of the new UK and SA SARS-CoV-2 variants

“…In contrast to the above proteases, the neutrophil elastase is enriched in the nose of humans compared to other tissues ( 19 ) and neutrophils, a source for this elastase, are recruited to the nose in SARS-CoV-2 infection ( 20 ). Indeed, the now worldwide dominant Asp614Gly variant, introduced a new elastase proteolysis site in the spike protein ( 2, 21 ).…”

“…Proteomic analyses identified five proteins with increased expression in nasopharyngeal swab of subjects with high polymerase chain reaction titer for SARS-CoV-2 ( 20 ). Among these five proteins is neutrophil elastase, whose levels increased 3-fold in SARS-CoV-2 infected vs. noninfected individuals.…”

“…Furthermore, there is a 10-fold increase in neutrophil number in swabs from infected individuals. Elastase was also found to be critical for accelerating viral entry as well as inducing hypertension, thrombosis and vasculitis ( 20, 35 ). As there are several approved elastase inhibitors, including Sivelestat (which is approved for acute respiratory syndrome), Alvestat (α1-antitrypsin) and Roseltide, the use of these inhibitors, perhaps as intranasal spray or drops, should be considered.…”

Role of Multiomics Data to Understand Host–Pathogen Interactions in COVID-19 Pathogenesis

“…In agreement with other studies, these belonged to pathways involved in neutrophil degranulation, antimicrobial activity, and other elements of the innate immune system. 63 …”

“…Overall, they specifically trigger immune cells to release cytokines, 64 many different antimicrobial peptides, and trigger the formation of reactive oxygen species that collectively act as early antiviral defenses. 64 The same study identified highly expressed azurophil granule proteins myeloperoxidase (MPO), elastase (ELANE), cathepsin G (CTSG), azurocidin 1 (AZU1), and proteinase 3 (PRTN3) that are collectively thought to play critical roles in viral clearance, 63 although it is completely unknown how neutrophils and their activation followed by degranulation play a role in modulating the immune response in the case of SARS CoV-2 infection. A different study from oro- and NPS samples detected three proteins to be present exclusively in COVID-19 patients, namely tapasin, MHC II DRβ chain, and guanylate-binding protein 1 (GBP1).…”