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Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.
Sacco, Keith; Castagnoli, Riccardo; Vakkilainen, Svetlana; Liu, Can; Delmonte, Ottavia M; Oguz, Cihan; Kaplan, Ian M; Alehashemi, Sara; Burbelo, Peter D; Bhuyan, Farzana; de Jesus, Adriana A; Dobbs, Kerry; Rosen, Lindsey B; Cheng, Aristine; Shaw, Elana; Vakkilainen, Mikko S; Pala, Francesca; Lack, Justin; Zhang, Yu; Fink, Danielle L; Oikonomou, Vasileios; Snow, Andrew L; Dalgard, Clifton L; Chen, Jinguo; Sellers, Brian A; Montealegre Sanchez, Gina A; Barron, Karyl; Rey-Jurado, Emma; Vial, Cecilia; Poli, Maria Cecilia; Licari, Amelia; Montagna, Daniela; Marseglia, Gian Luigi; Licciardi, Francesco; Ramenghi, Ugo; Discepolo, Valentina; Lo Vecchio, Andrea; Guarino, Alfredo; Eisenstein, Eli M; Imberti, Luisa; Sottini, Alessandra; Biondi, Andrea; Mató, Sayonara; Gerstbacher, Dana; Truong, Meng; Stack, Michael A; Magliocco, Mary; Bosticardo, Marita; Kawai, Tomoki; Danielson, Jeffrey J.
  • Sacco K; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Castagnoli R; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Vakkilainen S; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Liu C; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Delmonte OM; Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Oguz C; Graduate Program in Biological Sciences, University of Maryland, College Park, MD, USA.
  • Kaplan IM; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Alehashemi S; NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Burbelo PD; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD, USA.
  • Bhuyan F; Adaptive Biotechnologies, Seattle, WA, USA.
  • de Jesus AA; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dobbs K; National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
  • Rosen LB; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Cheng A; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Shaw E; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Vakkilainen MS; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Pala F; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Lack J; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhang Y; Department of Computer Science, Aalto University, Helsinki, Finland.
  • Fink DL; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Oikonomou V; Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Snow AL; NIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dalgard CL; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Chen J; Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Sellers BA; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Montealegre Sanchez GA; Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Barron K; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Rey-Jurado E; The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
  • Vial C; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.
  • Poli MC; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.
  • Licari A; Intramural Clinical Management and Operation Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Montagna D; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Marseglia GL; Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
  • Licciardi F; Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
  • Ramenghi U; Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
  • Discepolo V; Unidad de Inmunología y Reumatología, Hospital de niños Dr. Roberto del Río, Santiago, Chile.
  • Lo Vecchio A; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Guarino A; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Eisenstein EM; Laboratory of Immunology and Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Imberti L; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Sottini A; Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Città Della Salute E Della Scienza Di Torino, University of Turin, Turin, Italy.
  • Biondi A; Department of Pediatric and Public Health Sciences, Regina Margherita Children's Hospital, A.O.U. Città Della Salute E Della Scienza Di Torino, University of Turin, Turin, Italy.
  • Mató S; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
  • Gerstbacher D; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
  • Truong M; Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
  • Stack MA; Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
  • Magliocco M; CREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Bosticardo M; CREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Kawai T; Pediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN, University of Milano Bicocca, Fondazione MBBM, Ospedale San Gerardo, Monza, Italy.
  • Danielson JJ; Randall Children's Hospital at Legacy Emanuel, Portland, OR, USA.
Nat Med ; 28(5): 1050-1062, 2022 05.
Article in English | MEDLINE | ID: covidwho-1701612
ABSTRACT
Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Topics: Long Covid Limits: Child / Humans Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2022 Document Type: Article Affiliation country: S41591-022-01724-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Topics: Long Covid Limits: Child / Humans Language: English Journal: Nat Med Journal subject: Molecular Biology / Medicine Year: 2022 Document Type: Article Affiliation country: S41591-022-01724-3