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The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.
Syrimi, Eleni; Fennell, Eanna; Richter, Alex; Vrljicak, Pavle; Stark, Richard; Ott, Sascha; Murray, Paul G; Al-Abadi, Eslam; Chikermane, Ashish; Dawson, Pamela; Hackett, Scott; Jyothish, Deepthi; Kanthimathinathan, Hari Krishnan; Monaghan, Sean; Nagakumar, Prasad; Scholefield, Barnaby R; Welch, Steven; Khan, Naeem; Faustini, Sian; Davies, Kate; Zelek, Wioleta M; Kearns, Pamela; Taylor, Graham S.
  • Syrimi E; Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK.
  • Fennell E; Health Research Institute and the Bernal Institute, University of Limerick, Limerick, Ireland.
  • Richter A; Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK.
  • Vrljicak P; Warwick Medical School, University of Warwick, Coventry, UK.
  • Stark R; Bioinformatics Research Technology Platform, University of Warwick, Coventry, UK.
  • Ott S; Warwick Medical School, University of Warwick, Coventry, UK.
  • Murray PG; Bioinformatics Research Technology Platform, University of Warwick, Coventry, UK.
  • Al-Abadi E; Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK.
  • Chikermane A; Health Research Institute and the Bernal Institute, University of Limerick, Limerick, Ireland.
  • Dawson P; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Hackett S; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Jyothish D; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Kanthimathinathan HK; Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Monaghan S; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Nagakumar P; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Scholefield BR; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Welch S; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Khan N; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Faustini S; Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
  • Davies K; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
  • Zelek WM; Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
  • Kearns P; Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK.
  • Taylor GS; Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK.
iScience ; 24(11): 103215, 2021 Nov 19.
Article in English | MEDLINE | ID: covidwho-1446746
ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.
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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Type of study: Risk factors Language: English Journal: IScience Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Type of study: Risk factors Language: English Journal: IScience Year: 2021
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