Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children
IntroductionMultisystem 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...
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| Format: | Article |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1050804/full |
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| author | Nathella Pavan Kumar Aishwarya Venkataraman Poovazhagi Varadarjan Arul Nancy Anuradha Rajamanickam Elilarasi Selladurai Thangavelu Sankaralingam Kannan Thiruvengadam Ramya Selvam Akshith Thimmaiah Suresh Natarajan Ganesh Ramaswamy Sulochana Putlibai Kalaimaran Sadasivam Balasubramanian Sundaram Syed Hissar Uma Devi Ranganathan Thomas B. Nutman Subash Babu Subash Babu |
| author_facet | Nathella Pavan Kumar Aishwarya Venkataraman Poovazhagi Varadarjan Arul Nancy Anuradha Rajamanickam Elilarasi Selladurai Thangavelu Sankaralingam Kannan Thiruvengadam Ramya Selvam Akshith Thimmaiah Suresh Natarajan Ganesh Ramaswamy Sulochana Putlibai Kalaimaran Sadasivam Balasubramanian Sundaram Syed Hissar Uma Devi Ranganathan Thomas B. Nutman Subash Babu Subash Babu |
| author_sort | Nathella Pavan Kumar |
| collection | DOAJ |
| description | IntroductionMultisystem 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.MethodsTo 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).ResultsChildren 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.DiscussionOur 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. |
| first_indexed | 2024-04-11T07:16:12Z |
| format | Article |
| id | doaj.art-fd468096e8cd42619a7d3b167d173120 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-11T07:16:12Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-fd468096e8cd42619a7d3b167d1731202022-12-22T04:37:57ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-12-01910.3389/fmed.2022.10508041050804Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in childrenNathella Pavan Kumar0Aishwarya Venkataraman1Poovazhagi Varadarjan2Arul Nancy3Anuradha Rajamanickam4Elilarasi Selladurai5Thangavelu Sankaralingam6Kannan Thiruvengadam7Ramya Selvam8Akshith Thimmaiah9Suresh Natarajan10Ganesh Ramaswamy11Sulochana Putlibai12Kalaimaran Sadasivam13Balasubramanian Sundaram14Syed Hissar15Uma Devi Ranganathan16Thomas B. Nutman17Subash Babu18Subash Babu19ICMR – National Institute for Research in Tuberculosis, Chennai, IndiaICMR – National Institute for Research in Tuberculosis, Chennai, IndiaInstitute of Child Health and Hospital for Children, Chennai, IndiaNational Institutes of Health-National Institute for Research in Tuberculosis – International Center for Excellence in Research, Chennai, IndiaNational Institutes of Health-National Institute for Research in Tuberculosis – International Center for Excellence in Research, Chennai, IndiaInstitute of Child Health and Hospital for Children, Chennai, IndiaDr. Mehta’s Children’s Hospital, Chennai, IndiaICMR – National Institute for Research in Tuberculosis, Chennai, IndiaDr. Mehta’s Children’s Hospital, Chennai, IndiaDr. Mehta’s Children’s Hospital, Chennai, IndiaRainbow Children’s Hospital, Chennai, IndiaRainbow Children’s Hospital, Chennai, IndiaKanchi Kamakoti CHILDS Trust Hospital, Chennai, IndiaKanchi Kamakoti CHILDS Trust Hospital, Chennai, IndiaKanchi Kamakoti CHILDS Trust Hospital, Chennai, IndiaICMR – National Institute for Research in Tuberculosis, Chennai, IndiaICMR – National Institute for Research in Tuberculosis, Chennai, IndiaLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesNational Institutes of Health-National Institute for Research in Tuberculosis – International Center for Excellence in Research, Chennai, IndiaLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesIntroductionMultisystem 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.MethodsTo 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).ResultsChildren 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.DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fmed.2022.1050804/fullMIS-CCOVID-19seropositiveMMPsbiomarker |
| spellingShingle | Nathella Pavan Kumar Aishwarya Venkataraman Poovazhagi Varadarjan Arul Nancy Anuradha Rajamanickam Elilarasi Selladurai Thangavelu Sankaralingam Kannan Thiruvengadam Ramya Selvam Akshith Thimmaiah Suresh Natarajan Ganesh Ramaswamy Sulochana Putlibai Kalaimaran Sadasivam Balasubramanian Sundaram Syed Hissar Uma Devi Ranganathan Thomas B. Nutman Subash Babu Subash Babu Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children Frontiers in Medicine MIS-C COVID-19 seropositive MMPs biomarker |
| 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 | MIS-C COVID-19 seropositive MMPs biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1050804/full |
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