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

doi:10.3389/fmed.2022.1050804

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

Front Med (Lausanne). 2022 Dec 5:9:1050804. doi: 10.3389/fmed.2022.1050804. eCollection 2022.

Authors

Nathella Pavan Kumar¹, Aishwarya Venkataraman¹, Poovazhagi Varadarjan², Arul Nancy³, Anuradha Rajamanickam³, Elilarasi Selladurai², Thangavelu Sankaralingam⁴, Kannan Thiruvengadam¹, Ramya Selvam⁴, Akshith Thimmaiah⁴, Suresh Natarajan⁵, Ganesh Ramaswamy⁵, Sulochana Putlibai⁶, Kalaimaran Sadasivam⁶, Balasubramanian Sundaram⁶, Syed Hissar¹, Uma Devi Ranganathan¹, Thomas B Nutman⁷, Subash Babu^{3

7}

Affiliations

¹ ICMR - National Institute for Research in Tuberculosis, Chennai, India.
² Institute of Child Health and Hospital for Children, Chennai, India.
³ National Institutes of Health-National Institute for Research in Tuberculosis - International Center for Excellence in Research, Chennai, India.
⁴ Dr. Mehta's Children's Hospital, Chennai, India.
⁵ Rainbow Children's Hospital, Chennai, India.
⁶ Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India.
⁷ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

Abstract

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.

Keywords: COVID-19; MIS-C; MMPs; biomarker; seropositive.

Copyright © 2022 Pavan Kumar, Venkataraman, Varadarjan, Nancy, Rajamanickam, Selladurai, Sankaralingam, Thiruvengadam, Selvam, Thimmaiah, Natarajan, Ramaswamy, Putlibai, Sadasivam, Sundaram, Hissar, Ranganathan, Nutman and Babu.