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

Autor:	Dos Santos F; Department of Anesthesiology, School of Medicine, University of California, San Diego, CA, United States., Li JB; Department of Bioengineering, University of California, San Diego, CA, United States., Juocys N; Department of Anesthesiology, School of Medicine, University of California, San Diego, CA, United States.; Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (InCor-FMUSP), São Paulo, Brazil., Mazor R; Department of Anesthesiology, School of Medicine, University of California, San Diego, CA, United States., Beretta L; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, United States., Coufal NG; Department of Pediatrics, School of Medicine, University of California, San Diego, CA, United States., Lam MTY; Department of Medicine, School of Medicine, University of California, San Diego, CA, United States., Odish MF; Department of Medicine, School of Medicine, University of California, San Diego, CA, United States., Irigoyen MC; Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (InCor-FMUSP), São Paulo, Brazil., O'Donoghue AJ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA, United States., Aletti F; Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São Josê dos Campos, Brazil., Kistler EB; Department of Anesthesiology, School of Medicine, University of California, San Diego, CA, United States.; Department of Anesthesiology and Critical Care, VA San Diego Healthcare System, San Diego, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2023 Jan 11; Vol. 9, pp. 1051471. Date of Electronic Publication: 2023 Jan 11 (Print Publication: 2022).
DOI:	10.3389/fmolb.2022.1051471
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Dos Santos, Li, Juocys, Mazor, Beretta, Coufal, Lam, Odish, Irigoyen, O’Donoghue, Aletti and Kistler.)
Databáze:	MEDLINE
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