No expansion of MIS-c associated TCR Vβ 21.3+ T-cells in pediatric Post-COVID condition

Adam J Tulling1, Marloes G Holierhoek1, Savannah N van der Kroft1

  • 1Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.

Immunology Letters
|June 3, 2026
PubMed

Insights

Pediatric post-COVID Condition (PPCC) lacks a clear cause. Unlike MIS-C, PPCC patients do not show T-cell Vβ21.3 expansion, suggesting different underlying mechanisms for these post-COVID complications in children.

Area of Science:

  • Immunology
  • Pediatrics
  • Virology

Background:

  • Pediatric post-COVID Condition (PPCC) etiology is unknown.
  • Multisystem Inflammatory Syndrome in Children (MIS-C) is a known SARS-CoV-2 complication.
  • MIS-C involves expansion of polyclonal TCR Vβ 21.3+ (TRBV11-2) T-cells.

Purpose of the Study:

  • To investigate the T-cell Vβ 21.3 expression in PPCC.
  • To compare T-cell profiles in PPCC, MIS-C, acute COVID-19, and healthy children.
  • To explore potential shared or distinct pathophysiologies between PPCC and MIS-C.

Main Methods:

  • Flow cytometry analysis.
  • Quantification of TCR Vβ 21.3+ T-cells within activated HLA-DR+/Ki67+ T-cells.
  • Study included 86 PPCC, 32 MIS-C, 7 acute COVID-19, and 15 healthy pediatric controls.

Main Results:

  • 78% of MIS-C patients (25/32) showed enrichment of Vβ21.3+ T-cells within activated T-cells.
  • No enrichment of Vβ21.3 expressing cells was observed in PPCC patients.
  • T-cell profiles differed significantly between MIS-C and PPCC groups.

Conclusions:

  • The findings argue against a shared T-cell expansion pathophysiology between MIS-C and PPCC.
  • Distinct immune responses may underlie different post-COVID conditions in children.
  • Further research is needed to elucidate PPCC pathogenesis.

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