Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status

BackgroundSystemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases...

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Main Authors: Stefano Brusa, Daniela Terracciano, Dario Bruzzese, Mariano Fiorenza, Lucia Stanziola, Biagio Pinchera, Valeria Valente, Ivan Gentile, Antonio Cittadini, Ilaria Mormile, Mauro Mormile, Giuseppe Portella
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2022.1034288/full
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author Stefano Brusa
Daniela Terracciano
Dario Bruzzese
Mariano Fiorenza
Lucia Stanziola
Biagio Pinchera
Valeria Valente
Ivan Gentile
Antonio Cittadini
Ilaria Mormile
Mauro Mormile
Giuseppe Portella
author_facet Stefano Brusa
Daniela Terracciano
Dario Bruzzese
Mariano Fiorenza
Lucia Stanziola
Biagio Pinchera
Valeria Valente
Ivan Gentile
Antonio Cittadini
Ilaria Mormile
Mauro Mormile
Giuseppe Portella
author_sort Stefano Brusa
collection DOAJ
description BackgroundSystemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients.MethodsNinety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support.ResultsSerum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4–9.5) vs. 7.1 (4.5–9.9), p = 0.782; TIMP-1: 298.1 (20.5–460) vs. 222.2 (28.5–452.8), p = 0.01; HA: 117.1 (55.4–193.7) vs. 75.1 (36.9–141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9–44.5) vs. 9.3 (3.4–33.8), p = 0.039 and 373 (282–465) vs. 289 (218–383), p = 0.013, respectively].ConclusionIn patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.
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spelling doaj.art-d93a1d6fb012425fa203062be6b957922022-12-22T03:44:21ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-11-01910.3389/fmed.2022.10342881034288Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity statusStefano Brusa0Daniela Terracciano1Dario Bruzzese2Mariano Fiorenza3Lucia Stanziola4Biagio Pinchera5Valeria Valente6Ivan Gentile7Antonio Cittadini8Ilaria Mormile9Mauro Mormile10Giuseppe Portella11Department of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Public Health, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyDepartment of Translational Medical Science, University of Naples Federico II, Naples, ItalyBackgroundSystemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients.MethodsNinety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support.ResultsSerum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score <5 [PIIINP: 7.2 (5.4–9.5) vs. 7.1 (4.5–9.9), p = 0.782; TIMP-1: 298.1 (20.5–460) vs. 222.2 (28.5–452.8), p = 0.01; HA: 117.1 (55.4–193.7) vs. 75.1 (36.9–141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score < 5 [15.8 (9–44.5) vs. 9.3 (3.4–33.8), p = 0.039 and 373 (282–465) vs. 289 (218–383), p = 0.013, respectively].ConclusionIn patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.https://www.frontiersin.org/articles/10.3389/fmed.2022.1034288/fullCOVID-19fibrosisTIMP-1collagen metabolitesextrcellular matrix remodelling biomarkers
spellingShingle Stefano Brusa
Daniela Terracciano
Dario Bruzzese
Mariano Fiorenza
Lucia Stanziola
Biagio Pinchera
Valeria Valente
Ivan Gentile
Antonio Cittadini
Ilaria Mormile
Mauro Mormile
Giuseppe Portella
Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
Frontiers in Medicine
COVID-19
fibrosis
TIMP-1
collagen metabolites
extrcellular matrix remodelling biomarkers
title Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
title_full Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
title_fullStr Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
title_full_unstemmed Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
title_short Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
title_sort circulating tissue inhibitor of metalloproteinases 1 timp 1 at covid 19 onset predicts severity status
topic COVID-19
fibrosis
TIMP-1
collagen metabolites
extrcellular matrix remodelling biomarkers
url https://www.frontiersin.org/articles/10.3389/fmed.2022.1034288/full
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