Frontiers in Medicine (Dec 2022)

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

  • 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

DOI
https://doi.org/10.3389/fmed.2022.1050804
Journal volume & issue
Vol. 9

Abstract

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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.

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