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Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children

INTRODUCTION: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in ma...

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Autores principales: Pavan Kumar, Nathella, Venkataraman, Aishwarya, Varadarjan, Poovazhagi, Nancy, Arul, Rajamanickam, Anuradha, Selladurai, Elilarasi, Sankaralingam, Thangavelu, Thiruvengadam, Kannan, Selvam, Ramya, Thimmaiah, Akshith, Natarajan, Suresh, Ramaswamy, Ganesh, Putlibai, Sulochana, Sadasivam, Kalaimaran, Sundaram, Balasubramanian, Hissar, Syed, Ranganathan, Uma Devi, Nutman, Thomas B., Babu, Subash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760695/
https://www.ncbi.nlm.nih.gov/pubmed/36544496
http://dx.doi.org/10.3389/fmed.2022.1050804
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author Pavan Kumar, Nathella
Venkataraman, Aishwarya
Varadarjan, Poovazhagi
Nancy, Arul
Rajamanickam, Anuradha
Selladurai, Elilarasi
Sankaralingam, Thangavelu
Thiruvengadam, Kannan
Selvam, Ramya
Thimmaiah, Akshith
Natarajan, Suresh
Ramaswamy, Ganesh
Putlibai, Sulochana
Sadasivam, Kalaimaran
Sundaram, Balasubramanian
Hissar, Syed
Ranganathan, Uma Devi
Nutman, Thomas B.
Babu, Subash
author_facet Pavan Kumar, Nathella
Venkataraman, Aishwarya
Varadarjan, Poovazhagi
Nancy, Arul
Rajamanickam, Anuradha
Selladurai, Elilarasi
Sankaralingam, Thangavelu
Thiruvengadam, Kannan
Selvam, Ramya
Thimmaiah, Akshith
Natarajan, Suresh
Ramaswamy, Ganesh
Putlibai, Sulochana
Sadasivam, Kalaimaran
Sundaram, Balasubramanian
Hissar, Syed
Ranganathan, Uma Devi
Nutman, Thomas B.
Babu, Subash
author_sort Pavan Kumar, Nathella
collection PubMed
description INTRODUCTION: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. METHODS: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). RESULTS: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. DISCUSSION: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation.
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spelling pubmed-97606952022-12-20 Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children Pavan Kumar, Nathella Venkataraman, Aishwarya Varadarjan, Poovazhagi Nancy, Arul Rajamanickam, Anuradha Selladurai, Elilarasi Sankaralingam, Thangavelu Thiruvengadam, Kannan Selvam, Ramya Thimmaiah, Akshith Natarajan, Suresh Ramaswamy, Ganesh Putlibai, Sulochana Sadasivam, Kalaimaran Sundaram, Balasubramanian Hissar, Syed Ranganathan, Uma Devi Nutman, Thomas B. Babu, Subash Front Med (Lausanne) Medicine INTRODUCTION: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. METHODS: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). RESULTS: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. DISCUSSION: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation. Frontiers Media S.A. 2022-12-05 /pmc/articles/PMC9760695/ /pubmed/36544496 http://dx.doi.org/10.3389/fmed.2022.1050804 Text en Copyright © 2022 Pavan Kumar, Venkataraman, Varadarjan, Nancy, Rajamanickam, Selladurai, Sankaralingam, Thiruvengadam, Selvam, Thimmaiah, Natarajan, Ramaswamy, Putlibai, Sadasivam, Sundaram, Hissar, Ranganathan, Nutman and Babu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Pavan Kumar, Nathella
Venkataraman, Aishwarya
Varadarjan, Poovazhagi
Nancy, Arul
Rajamanickam, Anuradha
Selladurai, Elilarasi
Sankaralingam, Thangavelu
Thiruvengadam, Kannan
Selvam, Ramya
Thimmaiah, Akshith
Natarajan, Suresh
Ramaswamy, Ganesh
Putlibai, Sulochana
Sadasivam, Kalaimaran
Sundaram, Balasubramanian
Hissar, Syed
Ranganathan, Uma Devi
Nutman, Thomas B.
Babu, Subash
Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title_full Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title_fullStr Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title_full_unstemmed Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title_short Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
title_sort role of matrix metalloproteinases in multi-system inflammatory syndrome and acute covid-19 in children
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760695/
https://www.ncbi.nlm.nih.gov/pubmed/36544496
http://dx.doi.org/10.3389/fmed.2022.1050804
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