Dataset Information

Dysregulation of circulating protease activity in COVID-19-associated superinfection

ABSTRACT: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis and septic shock. Our past studies demonstrated that dysregulated systemic proteolysis is associated with the pathological mechanism in bacterial septic shock. Thus, here we perform shotgun proteomics and peptidomics analysis by LC-MS/MS to identify and quantify the circulating protein and peptide profile of COVID-19 patient plasma. Plasma samples from four COVID-19 patients were collected at different time points of their ICU stay, including samples from a patient with COVID-19-induced sepsis and bacterial superinfection. By combining mass spectrometry analysis with enzymatic activity assays, our study elucidates the possible pathological involvement of proteolysis in COVID-19-induced sepsis, with particular insight into the dyregulation of protease-mediated systems, such as the coagulation cascade.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Covid-19

SUBMITTER: Joyce Li

LAB HEAD: Erik B. Kistler

PROVIDER: PXD029181 | Pride | 2023-03-10

REPOSITORIES: Pride

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Publications

Plasma enzymatic activity, proteomics and peptidomics in COVID-19-induced sepsis: A novel approach for the analysis of hemostasis.

Dos Santos Fernando F Li Joyce B JB Juocys Nathalia N Mazor Rafi R Beretta Laura L Coufal Nicole G NG Lam Michael T Y MTY Odish Mazen F MF Irigoyen Maria Claudia MC O'Donoghue Anthony J AJ Aletti Federico F Kistler Erik B EB

Frontiers in molecular biosciences 20230111

<b>Introduction:</b> Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). <b>Methods:</b> Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center ...[more]

PMID: 36710882

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Project description:Background: COVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks.We employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing COVID-19, sepsis, and sepsis-induced ARDS. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS.Results: Our investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across 3 diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes.Our investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes novel avenues for targeted therapies.

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