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

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art_SANTOS_Plasma_enzymatic_activity_proteomics_and_peptidomics_in_COVID19induced_.PDF (3.11 MB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
SANTOS, Fernando Dos
LI, Joyce B. B.
MAZOR, Rafi
BERETTA, Laura
COUFAL, Nicole G.
LAM, Michael T. Y.
ODISH, Mazen F.
O'DONOGHUE, Anthony J.
Citação
FRONTIERS IN MOLECULAR BIOSCIENCES, v.9, article ID 1051471, 13p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Introduction: 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).Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained for the collection of blood samples and de-identified use of the data. Blood samples were collected at multiple time points and analyzed to quantify a) the circulating proteome and peptidome by mass spectrometry; b) the aminopeptidase activity in plasma; and c) the endopeptidase activity in plasma using fluorogenic substrates that are cleaved by trypsin-like endopeptidases, specific clotting factors and plasmin. The one patient who died was diagnosed with bacterial superinfection on day 7 after beginning of the study.Results: Spikes in protease activity (factor VII, trypsin-like activity), and corresponding increases in the intensity of peptides derived by hydrolysis of plasma proteins, especially of fibrinogen degradation products and downregulation of endogenous protease inhibitors were detected on day 7 for the patient who died. The activity of the analyzed proteases was stable in survivors.Discussion: The combination of multiomics and enzymatic activity quantification enabled to i) hypothesize that elevated proteolysis occurs in COVID-19-induced septic shock with bacterial superinfection, and ii) provide additional insight into malfunctioning protease-mediated systems, such as hemostasis.
Palavras-chave
COVID-19, sepsis, proteolysis, enzymatic activity, peptidomics, proteomics
URI
https://observatorio.fm.usp.br/handle/OPI/53305
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - COVID-19
Artigos e Materiais de Revistas Científicas - LIM/59
Artigos e Materiais de Revistas Científicas - LIM/65
Artigos e Materiais de Revistas Científicas - ODS/03