Pathogenesis of hyperinflammatory syndrome associated with COVID-19 in children
The first reports about COVID-19 suggested that children infected with SARS-CoV-2 often presented with milder symptoms than adults. However, subsequently several studies from Europe and the USA have reported that in rare cases children can develop a severe hyperinflammatory syndrome (MIS-C). These children present with high fever, and other symptoms previously associated with Kawasaki disease. Kawasaki disease involves production of self-reactive antibodies during the acute immune response to a viral infection. Previous studies of Kawasaki disease showed an imbalance of interleukin (IL)-17-producing T cells and regulatory T cells during the acute phase of the disease.
Only few studies about MIS-C in children associated with COVID-19 have been published so far. In one of these studies, Camila Rosat Consiglio and colleagues (PI: Petter Brodin) performed a systems-level analysis of immune cells, cytokines, and antibodies, and compared blood from children presenting with MIS-C with children with mild SARS-CoV-2 infection, children with Kawasaki disease, and healthy children (the healthy children were enrolled prior to the COVID-19 pandemic). Consiglio and colleagues found that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19. The results also showed that the inflammatory response in MIS-C shares several features with Kawasaki disease but differs from Kawasaki in some respects, for example T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. The authors conclude that T cell subsets discriminate Kawasaki disease patients from MIS-C and that while IL-17A drives Kawasaki, it is not driving MIS-C hyperinflammation. In summary, the autoantibody profiling suggested multiple autoantibodies that could be involved in the pathogenesis of MIS-C and be important for the future treatment options for children with the hyperinflammatory syndrome.
The researchers have deposited datasets from their study and supplementary tables including multiple omics data from plasma protein expression (Olink- NPX-values, FACS, and autoantibodies) in the SciLifeLab Data Repository under DOI: 10.17044/scilifelab.13181273. The scripts to reproduce the analyses presented in each figure of the paper were made available on Github.
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This project has received funding from the Knut and Alice Wallenberg Foundation (KAW) to SciLifeLab, Bure Equity AB and Jonas and Christina af Jochnick Foundation to Karolinska Institutet and the SciLifeLab/KAW national COVID-19 research program project grant (P.B.) Children’s Hospital “Bambino Gesu”, 5 X mille 2019, ricerca corrente 2020 (N.C.) and ricerca corrente 2019 (P.P).
Consiglio, C. R., Cotugno, N., Sardh, F., Pou, C., Amodio, D., Rodriguez, L., Tan, Z., Zicari, S., Ruggiero, A., Rubens Pascucci, G., Santilli, V., Campbell, T., Bryceson, Y., Eriksson, D., Wang, J., Marchesi, A., Lakshmikanth, T., Campana, A., Villani, A., Rossi, P., the CACTUS Study Team, Landegren, N., Palma, P., & Brodin, P. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell, 183 (4), P968-981.e7 (2020).
Multiple omics data:
- Plasma protein expression (Olink - NPX values)