Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3570
• Main Authors: Pagani, Lisa, Chinello, Clizia, Risca, Giulia, Capitoli, Giulia, Criscuolo, Lucrezia, Lombardi, Andrea, Ungaro, Riccardo, Mangioni, Davide, Piga, Isabella, Muscatello, Antonio, Blasi, Francesco, Favalli, Andrea, Martinovic, Martina, Gori, Andrea, Bandera, Alessandra, Grifantini, Renata, Magni, Fulvio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.02.2023; MDPI
• Subjects: Analysis; Asymptomatic; Care and treatment; Chromatography, Liquid; Classification; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - metabolism; Development and progression; Disease transmission; Health aspects; Humans; Infections; Investigations; Mass spectrometry; Patient Acuity; Patients; Plasma; Proteins; Proteomics; Proteomics - methods; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Tandem Mass Spectrometry; Variables; Germany; COVID-19; SARS-CoV-2; proteomics; severe; mass spectrometry; plasma; blood
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043570

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to a wide range of clinical manifestations and determines the need for personalized and precision medicine. To better understand the biological determinants of this heterogeneity, we explored the plasma proteome of 43 COVID-19 patients with different outcomes by an untargeted liquid chromatography-mass spectrometry approach. The comparison between asymptomatic or pauci-symptomatic subjects (MILDs), and hospitalised patients in need of oxygen support therapy (SEVEREs) highlighted 29 proteins emerged as differentially expressed: 12 overexpressed in MILDs and 17 in SEVEREs. Moreover, a supervised analysis based on a decision-tree recognised three proteins (Fetuin-A, Ig lambda-2chain-C-region, Vitronectin) that are able to robustly discriminate between the two classes independently from the infection stage. In silico functional annotation of the 29 deregulated proteins pinpointed several functions possibly related to the severity; no pathway was associated exclusively to MILDs, while several only to SEVEREs, and some associated to both MILDs and SEVEREs; SARS-CoV-2 signalling pathway was significantly enriched by proteins up-expressed in SEVEREs (SAA1/2, CRP, HP, LRG1) and in MILDs (GSN, HRG). In conclusion, our analysis could provide key information for ‘proteomically’ defining possible upstream mechanisms and mediators triggering or limiting the domino effect of the immune-related response and characterizing severe exacerbations.