iciHHV-6 in a Patient With Multisystem Inflammatory Syndrome in Children

Pediatrics. 2021 Sep;148(3):e2021051297. doi: 10.1542/peds.2021-051297. Epub 2021 Jun 2.


Multisystem inflammatory syndrome in children (MIS-C) is a serious, sometimes life-threatening late complication of coronavirus disease 2019 (COVID-19) with multiorgan involvement and evidence of immune activation. The pathogenesis of MIS-C is not known, nor is the pathogenesis of the severe organ damage that is the hallmark of MIS-C. Human herpesvirus 6 (HHV-6), the virus responsible for roseola, is a ubiquitous herpesvirus that causes close to universal infection by the age of 3 years. HHV-6 remains latent for life and can be activated during inflammatory states, by other viruses, and by host cell apoptosis. HHV-6 has been associated with end-organ diseases, including hepatitis, carditis, and encephalitis. In addition, ∼1% of people have inherited chromosomally integrated human herpesvirus 6 (iciHHV-6), which is HHV-6 that has been integrated into chromosomal telomeric regions and is transmitted through the germ line. iciHHV-6 can be reactivated and has been associated with altered immune responses. We report here a case of MIS-C in which an initial high HHV-6 DNA polymerase chain reaction viral load assay prompted testing for iciHHV-6, which yielded a positive result. Additional research may be warranted to determine if iciHHV-6 is commonly observed in patients with MIS-C and, if so, whether it may play a part in MIS-C pathogenesis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / virology*
  • COVID-19 Nucleic Acid Testing
  • Child
  • DNA, Viral / isolation & purification
  • Herpesvirus 6, Human* / genetics
  • Herpesvirus 6, Human* / isolation & purification
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Roseolovirus Infections / virology*
  • Systemic Inflammatory Response Syndrome / virology*
  • Telomere / virology
  • Viral Load
  • Virus Latency


  • DNA, Viral

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related