20 Mar, 2025
Researchers Identify Epstein-Barr Virus Reactivation as a Key Trigger for MIS-C
A team of scientists from Charité—Universitätsmedizin Berlin and the German Rheumatology Research Center (DRFZ) has uncovered a crucial link between Multisystem Inflammatory Syndrome in Children (MIS-C) and the Epstein-Barr virus (EBV). Their findings, published in Nature, provide new insights into the causes of this rare but severe inflammatory condition that can develop in children weeks after a COVID-19 infection.
While most children experience mild COVID-19 symptoms, a small percentage can develop MIS-C, a condition where the immune system becomes hyperactive and attacks the body’s organs. This can lead to serious complications such as heart failure, high fever, and skin rashes1. Many affected children require hospitalization, with nearly half needing intensive care. Until now, the precise cause of this excessive immune response remained unclear.
The Role of Epstein-Barr Virus
The Epstein-Barr virus, which causes infectious mononucleosis ("mono"), is present in most people and typically remains dormant in the body after an initial infection2. However, researchers have now found that in children with MIS-C, EBV reactivates, likely due to COVID-19 disrupting immune regulation. Instead of keeping the virus in check, the immune system fails to control it, leading to a dangerous inflammatory response.
A study involving 145 children treated for MIS-C across hospitals in Germany, France, Italy, Türkiye, and Chile revealed high levels of EBV in their blood, along with antibodies and immune cells actively fighting the virus. In contrast, 105 children who had COVID-19 but did not develop MIS-C showed no such EBV reactivation.
TGFβ: The Key Messenger Behind MIS-C
Further investigation identified an immune-suppressing molecule called transforming growth factor beta (TGFβ) as a major factor in this process3. COVID-19 infection leads to elevated TGFβ levels, which weaken immune cells' ability to eliminate EBV-infected cells. As the virus multiplies unchecked, the body responds by producing more immune cells—yet these cells remain ineffective, causing widespread inflammation that can lead to organ damage.
Potential Treatment Breakthroughs
Current MIS-C treatments focus on reducing inflammation using immunoglobulins and corticosteroids. However, researchers now propose that blocking TGFβ early could be a more targeted approach to preventing the severe immune reaction seen in MIS-C.
Beyond MIS-C, these findings could have broader implications for long COVID and severe COVID-19 cases in adults. Evidence suggests that reactivated dormant viruses might also contribute to long COVID symptoms. If so, TGFβ inhibitors could become a potential treatment option for multiple post-COVID complications.
Further research is needed to determine the effectiveness of TGFβ inhibitors in clinical settings, but this discovery marks an important step toward understanding and managing COVID-related inflammatory conditions.
References:
- La Torre F, Taddio A, Conti C, Cattalini M. Multi-Inflammatory Syndrome in Children (MIS-C) in 2023: Is It Time to Forget about It? Children (Basel). 2023 May 31;10(6):980. doi: 10.3390/children10060980. PMID: 37371212; PMCID: PMC10297102.
- Vedham V, Verma M, and Mahabir S (2015). Early-life exposures to infectious agents and later cancer development. Cancer Med 4, 1908–1922
- Goetzke CC et al. TGFβ links EBV to multisystem inflammatory syndrome in children, Nature (2025).