While children were observed to experience less severe symptoms of Coronavirus 2019 (COVID-19) than adults, SARS-CoV-2 infection can lead to a severe hyperinflammatory condition known as multisystem inflammatory syndrome in children (MIS-C), which typically occurs 4-8 weeks post-infection2. MIS-C is marked by specific T cell expansion and systemic hyperinflammation, yet its underlying mechanisms remained largely unclear. A recent study reveals that acute MIS-C is associated with impaired reactivation of virus-reactive memory T cells, which is linked to elevated serum levels of the cytokine transforming growth factor β (TGFβ)3. This impairment leads to functional changes in T cells, B cells, and monocytes, which can potentially be reversed by blocking TGFβ. Moreover, signs of Epstein-Barr virus (EBV) reactivation have been observed in MIS-C patients, whose immune systems are hindered by TGFβ to suppress EBV, leading to hyperinflammation. This study highlights the complex role TGFβ plays in driving inflammation and suggests TGFβ as a promising treatment target for MIS-C as well as other COVID-related complications.
References
2. Okuducu YK, et al. Clin. Chest Med 2024;45:675–684. 3. Goetzke CC, et al. Nature 2025. https://doi.org/10.1038/s41586-025-08697-6.
