Multisystem inflammatory syndrome in children characterized by enhanced antigen-specific T-cell expression of cytokines and its reversal following recovery

Nathella Pavan Kumar; Kadar M Abbas; Rachel M Renji; Aishwarya Venkataraman; Arul Nancy; Poovazhagi Varadarjan; Elilarasi Selladurai; Thankgavelu Sangaralingam; Ramya Selvam; Akshith Thimmaiah; Suresh Natarajan; Ganesh Ramasamy; Syed Hissar; Uma Devi Ranganathan; Thomas B Nutman; Subash Babu

doi:10.3389/fped.2023.1235342

Multisystem inflammatory syndrome in children characterized by enhanced antigen-specific T-cell expression of cytokines and its reversal following recovery

Front Pediatr. 2023 Dec 5:11:1235342. doi: 10.3389/fped.2023.1235342. eCollection 2023.

Authors

Nathella Pavan Kumar^#¹, Kadar M Abbas^#², Rachel M Renji², Aishwarya Venkataraman³, Arul Nancy², Poovazhagi Varadarjan⁴, Elilarasi Selladurai⁴, Thankgavelu Sangaralingam⁵, Ramya Selvam⁵, Akshith Thimmaiah⁵, Suresh Natarajan⁶, Ganesh Ramasamy⁶, Syed Hissar³, Uma Devi Ranganathan¹, Thomas B Nutman⁷, Subash Babu^{2

7}

Affiliations

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

^# Contributed equally.

Abstract

Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied.

Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections. Whole blood was stimulated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antigens and flow cytometry was performed to examine CD4⁺ and CD8⁺ T-cell responses.

Results: Children with MIS had higher frequencies of CD4⁺ and CD8⁺ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with COVID-19 and/or other infections. Children with COVID-19 also exhibited higher frequencies of CD4⁺ and CD8⁺ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with other infections. At 6-9 months following treatment and recovery, this enhanced response against SARS-CoV-2 antigens was down modulated in children with MIS.

Conclusion: Our study, therefore, provides evidence of enhanced activation of CD4⁺ and CD8⁺ T-cell responses in children with MIS and reversal following recovery.

Keywords: CD4+ T cells; CD8+ T cells; COVID-19; MIS-C; SARS-CoV-2; cellular immune responses.

Grants and funding

This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Health (NIH), National Institute of Research in Tuberculosis (NIRT), and the International Center for Excellence in Research (ICER).