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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSANTOS, Fernando Dos
dc.contributor.authorLI, Joyce B. B.
dc.contributor.authorJUOCYS, Nathalia
dc.contributor.authorMAZOR, Rafi
dc.contributor.authorBERETTA, Laura
dc.contributor.authorCOUFAL, Nicole G.
dc.contributor.authorLAM, Michael T. Y.
dc.contributor.authorODISH, Mazen F.
dc.contributor.authorIRIGOYEN, Maria Claudia
dc.contributor.authorO'DONOGHUE, Anthony J.
dc.contributor.authorALETTI, Federico
dc.contributor.authorKISTLER, Erik B.
dc.date.accessioned2023-04-14T18:15:23Z
dc.date.available2023-04-14T18:15:23Z
dc.date.issued2023
dc.description.abstractIntroduction: 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.eng
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipCalifornia Breast Cancer Research Program of the University of California, RGPO Grant [R01RG3766, R00RG2541]
dc.description.sponsorshipUS Army Medical Research Acquisition Activity (USAMRAA) Award [W81XWH-17-2-0047]
dc.identifier.citationFRONTIERS IN MOLECULAR BIOSCIENCES, v.9, article ID 1051471, 13p, 2023
dc.identifier.doi10.3389/fmolb.2022.1051471
dc.identifier.eissn2296-889X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/53305
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Molecular Biosciences
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectCOVID-19eng
dc.subjectsepsiseng
dc.subjectproteolysiseng
dc.subjectenzymatic activityeng
dc.subjectpeptidomicseng
dc.subjectproteomicseng
dc.subject.otherproteolysiseng
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.titlePlasma enzymatic activity, proteomics and peptidomics in COVID-19-induced sepsis: A novel approach for the analysis of hemostasiseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalSANTOS, Fernando Dos:Univ Calif San Diego, Sch Med, Dept Anesthesiol, San Diego, CA USA
hcfmusp.author.externalLI, Joyce B. B.:Univ Calif San Diego, Dept Bioengn, San Diego, CA USA
hcfmusp.author.externalMAZOR, Rafi:Univ Calif San Diego, Sch Med, Dept Anesthesiol, San Diego, CA USA
hcfmusp.author.externalBERETTA, Laura:Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA USA
hcfmusp.author.externalCOUFAL, Nicole G.:Univ Calif San Diego, Sch Med, Dept Pediat, San Diego, CA USA
hcfmusp.author.externalLAM, Michael T. Y.:Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA USA
hcfmusp.author.externalODISH, Mazen F.:Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA USA
hcfmusp.author.externalO'DONOGHUE, Anthony J.:Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA USA
hcfmusp.author.externalALETTI, Federico:Univ Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, Brazil
hcfmusp.author.externalKISTLER, Erik B.:Univ Calif San Diego, Sch Med, Dept Anesthesiol, San Diego, CA USA; VA San Diego Healthcare Syst, Dept Anesthesiol & Crit Care, San Diego, CA USA
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcNATHALIA JUOCYS DIAS MOREIRA
hcfmusp.contributor.author-fmusphcMARIA CLAUDIA COSTA IRIGOYEN
hcfmusp.description.articlenumber1051471
hcfmusp.description.volume9
hcfmusp.origemWOS
hcfmusp.origem.pubmed36710882
hcfmusp.origem.scopus2-s2.0-85146991210
hcfmusp.origem.wosWOS:000922571000001
hcfmusp.publisher.cityLAUSANNEeng
hcfmusp.publisher.countrySWITZERLANDeng
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Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - COVID-19
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