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Multi-omics approach identifies novel age-, time- and treatment-related immunopathological signatures in MIS-C and pediatric COVID-19
Keith Sacco; Riccardo Castagnoli; Svetlana Vakkilainen; Can Liu; Ottavia M. Delmonte; Cihan Oguz; Ian M. Kaplan; Sara Alehashemi; Peter D. Burbelo; Farzana Bhuyan; Adriana A. de Jesus; Kerry Dobbs; Lindsey B. Rosen; Aristine Cheng; Elana Shaw; Mikko S. Vakkilainen; Francesca Pala; Justin Lack; Yu Zhang; Danielle Fink; Vasileios Oikonomou; Andrew L. Snow; Clifton L. Dalgard; Jinguo Chen; Brian A. Sellers; Gina A. Montealegre Sanchez; Karyl Barron; Emma Rey; Maria Cecilia Vial; Maria Cecilia Poli; Amelia Licari; Daniela Montagna; Gian Luigi Marseglia; Francesco Licciardi; Ugo Ramenghi; Valentina Discepolo; Andrea Lo Vecchio; Alfredo Guarino; Eli M. Eisenstein; Luisa Imberti; Alessandra Sottini; Andrea Biondi; Sayonara Mato; Dana Gerstbacher; Meng Truong; Michael A. Stack; Mary Magliocco; Marita Bosticardo; Tomoki Kawai; Jefffrey J. Danielson; Tyler Hulett; Manor Askenazi; - NIAID Immune Response to COVID Group; - Chile MIS-C Group; - Pavia Pediatric COVID-19 Group; Jeffrey I Cohen; Helen C. Su; Douglas B. Kuhns; Michail S. Lionakis; Thomas M. Snyder; Steven M. Holland; Raphaela Goldbach-Mansky; John S. Tsang; Luigi D. Notarangelo.
Afiliación
  • Keith Sacco; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Riccardo Castagnoli; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Svetlana Vakkilainen; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Can Liu; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA, Graduate Program in Biological Sciences, Universit
  • Ottavia M. Delmonte; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Cihan Oguz; NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Ian M. Kaplan; Adaptive Biotechnologies, Seattle, WA 98109, USA
  • Sara Alehashemi; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Peter D. Burbelo; National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
  • Farzana Bhuyan; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Adriana A. de Jesus; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Kerry Dobbs; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Lindsey B. Rosen; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Aristine Cheng; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
  • Elana Shaw; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Mikko S. Vakkilainen; Department of Computer Science, Aalto University, Helsinki, Finland
  • Francesca Pala; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Justin Lack; NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Yu Zhang; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Danielle Fink; Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
  • Vasileios Oikonomou; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Andrew L. Snow; Department of Pharmacology & Molecular Therapeutics, Uniformed Services, University of the Health Sciences, Bethesda, MD 20892, USA.
  • Clifton L. Dalgard; Department of Pharmacology & Molecular Therapeutics, Uniformed Services, University of the Health Sciences, Bethesda, MD 20892, USA.
  • Jinguo Chen; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD 20892, USA
  • Brian A. Sellers; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD 20892, USA
  • Gina A. Montealegre Sanchez; Intramural Clinical Management and Operation Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Inst
  • Karyl Barron; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • Emma Rey; Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile
  • Maria Cecilia Vial; Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile
  • Maria Cecilia Poli; Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile; Unidad de Inmunologia y Reumatologia, Hospital de ninos Dr. Roberto del Rio, S
  • Amelia Licari; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavi
  • Daniela Montagna; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavi
  • Gian Luigi Marseglia; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavi
  • Francesco Licciardi; Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Citta Della Salute E Della Scienza Di Torino, University of Tu
  • Ugo Ramenghi; Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Citta Della Salute E Della Scienza Di Torino, University of Tu
  • Valentina Discepolo; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy
  • Andrea Lo Vecchio; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy
  • Alfredo Guarino; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy
  • Eli M. Eisenstein; Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel
  • Luisa Imberti; CREA (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy
  • Alessandra Sottini; CREA (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy
  • Andrea Biondi; Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM- Ospedale San
  • Sayonara Mato; Randall Children's Hospital at Legacy Emanuel, Portland, Portland, Oregon, OR 97227, USA
  • Dana Gerstbacher; Division of pediatric Rheumatology, Stanford Childrens Hospital, Stanford, CA 94304, USA
  • Meng Truong; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Michael A. Stack; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Mary Magliocco; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA
  • Marita Bosticardo; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Tomoki Kawai; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Jefffrey J. Danielson; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Tyler Hulett; CDI Laboratories, Antygen Division, Baltimore, MD MD 21205, USA
  • Manor Askenazi; CDI Laboratories, Antygen Division, Baltimore, MD MD 21205, USA
  • - NIAID Immune Response to COVID Group;
  • - Chile MIS-C Group;
  • - Pavia Pediatric COVID-19 Group;
  • Jeffrey I Cohen; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious diseases, National Institutes of Health, Bethesda, MD 20892, USA
  • Helen C. Su; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Douglas B. Kuhns; Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
  • Michail S. Lionakis; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Thomas M. Snyder; Adaptive Biotechnologies, Seattle, WA, USA
  • Steven M. Holland; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • Raphaela Goldbach-Mansky; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
  • John S. Tsang; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA; NIH Center for Human Immunology, NIAID, NIH, Bethe
  • Luigi D. Notarangelo; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, US
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21263853
ABSTRACT
Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, a multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in children with COVID-19 (n=105) and MIS-C (n=76). pCOVID-19 was characterized by enhanced type I IFN responses, and MIS-C by type II IFN- and NF-{kappa}B dependent responses, matrisome activation, and increased levels of Spike protein. Reduced levels of IL-33 in pCOVID-19, and of CCL22 in MIS-C suggested suppression of Th2 responses. Expansion of TRBV11-2 T-cell clonotypes in MIS-C was associated with inflammation and signatures of T-cell activation, and was reversed by glucocorticoids. The association of MIS-C with the combination of HLA A*02, B*35, C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load. Use of IVIG was identified as a confounding factor in the interpretation of autoantibody levels.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2021 Tipo del documento: Preprint