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Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19.
Vella, Laura A; Giles, Josephine R; Baxter, Amy E; Oldridge, Derek A; Diorio, Caroline; Kuri-Cervantes, Leticia; Alanio, Cécile; Pampena, M Betina; Wu, Jennifer E; Chen, Zeyu; Huang, Yinghui Jane; Anderson, Elizabeth M; Gouma, Sigrid; McNerney, Kevin O; Chase, Julie; Burudpakdee, Chakkapong; Lee, Jessica H; Apostolidis, Sokratis A; Huang, Alexander C; Mathew, Divij; Kuthuru, Oliva; Goodwin, Eileen C; Weirick, Madison E; Bolton, Marcus J; Arevalo, Claudia P; Ramos, Andre; Jasen, C J; Conrey, Peyton E; Sayed, Samir; Giannini, Heather M; D'Andrea, Kurt; Meyer, Nuala J; Behrens, Edward M; Bassiri, Hamid; Hensley, Scott E; Henrickson, Sarah E; Teachey, David T; Betts, Michael R; Wherry, E John.
  • Vella LA; Division of Infectious Diseases, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. vellal@chop.edu wherry@pennmedicine.upenn.edu.
  • Giles JR; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Baxter AE; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Oldridge DA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Diorio C; Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Kuri-Cervantes L; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Alanio C; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Pampena MB; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Wu JE; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Chen Z; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Huang YJ; Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Anderson EM; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Gouma S; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • McNerney KO; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Chase J; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Burudpakdee C; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Lee JH; Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Apostolidis SA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Huang AC; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Mathew D; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Kuthuru O; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Goodwin EC; Parker Institute for Cancer Immunotherapy at University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Weirick ME; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Bolton MJ; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Arevalo CP; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Ramos A; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Jasen CJ; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Conrey PE; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Sayed S; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Giannini HM; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • D'Andrea K; Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Meyer NJ; Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Behrens EM; Division of Rheumatology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Bassiri H; Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Hensley SE; Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Henrickson SE; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Teachey DT; Division of Rheumatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Betts MR; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  • Wherry EJ; Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sci Immunol ; 6(57)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1115087
Semantic information from SemMedBD (by NLM)
1. Mild disease PROCESS_OF Adult
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PROCESS_OF
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Adult
2. pediatric inflammatory multisystem syndrome CAUSES Shock
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pediatric inflammatory multisystem syndrome
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CAUSES
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Shock
3. pediatric inflammatory multisystem syndrome CAUSES Blood Vessel complications
Subject
pediatric inflammatory multisystem syndrome
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CAUSES
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Blood Vessel complications
4. Immune response PROCESS_OF hospitalized patients
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PROCESS_OF
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hospitalized patients
5. pediatric inflammatory multisystem syndrome PROCESS_OF Patients
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pediatric inflammatory multisystem syndrome
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6. Malaise PROCESS_OF Adult
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7. pediatric inflammatory multisystem syndrome PROCESS_OF Adult
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pediatric inflammatory multisystem syndrome
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8. COVID-19 PROCESS_OF Patients
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9. Respiratory Distress Syndrom PROCESS_OF C0030705
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11. pediatric inflammatory multisystem syndrome CAUSES Shock
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pediatric inflammatory multisystem syndrome
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Shock
12. pediatric inflammatory multisystem syndrome CAUSES Blood Vessel complications
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pediatric inflammatory multisystem syndrome
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Blood Vessel complications
13. Immune response PROCESS_OF hospitalized patients
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pediatric inflammatory multisystem syndrome
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16. pediatric inflammatory multisystem syndrome PROCESS_OF Adult
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pediatric inflammatory multisystem syndrome
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17. COVID-19 PROCESS_OF Patients
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ABSTRACT
Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Lymphocyte Activation / T-Lymphocytes / Systemic Inflammatory Response Syndrome / COVID-19 Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Young adult Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Lymphocyte Activation / T-Lymphocytes / Systemic Inflammatory Response Syndrome / COVID-19 Limits: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male / Young adult Language: English Year: 2021 Document Type: Article