ArticleNature communications2021
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction.
Registry-linked trialOpen access · goldAbstract read
In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05576714 (Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children), which is not on this map. Cited by 48 papers.
0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigation of Prognostic Biomarkers, Host Factors and Viral Factors for COVID-19 Associated Encephalopathy/Encephalitis and Multi-systemic Inflammatory Syndrome in Children
Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Tracking the soluble biomarkers of MIS-C and their association with clinical parameters and severity.Pediatric research · 2026Article
- MIS-C and Kawasaki disease: a shared spectrum of post-infectious hyperinflammation.Pediatric research · 2026Article
- MIS-C: Diagnosis, Management, and Outcomes.Open forum infectious diseases · 2026Review
- Mass spectrometry combined with machine learning identifies novel protein signatures as demonstrated with multisystem inflammatory syndrome in children.Scientific reports · 2025Article
- In depth characterisation of the proteome of MIS-C and post COVID-19 infection in children reveals inflammatory pathway activation and evidence of tissue damage.Journal of translational medicine · 2025Article
- A Method for Comparing Proteins Measured in Serum and Plasma by Olink Proximity Extension Assay.Molecular & cellular proteomics : MCP · 2025Article
- An Update on Multi-System Inflammatory Syndrome in Children.Current rheumatology reports · 2025Review
- NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Proteomic Signatures of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Narrative Review.Children (Basel, Switzerland) · 2024Review
- The Spectrum of Postacute Sequelae of COVID-19 in Children: From MIS-C to Long COVID.Annual review of virology · 2024Review
- The past 25 years in paediatric rheumatology: insights from monogenic diseases.Nature reviews. Rheumatology · 2024Review
- Clinical Significance of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Pediatric Patients: Insights into Their Utility in the Presence or Absence of Pre-Existing Heart Conditions.International journal of molecular sciences · 2024Review
- The complex landscape of immune dysregulation in multisystem inflammatory syndrome in children with COVID-19.Life medicine · 2024Review
- Elevated risk for psychiatric outcomes in pediatric patients with Multisystem Inflammatory Syndrome (MIS-C): A review of neuroinflammatory and psychosocial stressors.Brain, behavior, & immunity - health · 2024Review
- Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.Viruses · 2024Article
- Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children.Communications biology · 2024Article
- Severe pediatric COVID-19: a review from the clinical and immunopathophysiological perspectives.World journal of pediatrics : WJP · 2024Review
- Treatment of multisystem inflammatory syndrome in children.World journal of pediatrics : WJP · 2024Review
- Elevation of IL-17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
Corrections and comments
- Update of
Authors and funding
20 authors at 2 institutions in 1 country.
Caroline DiorioDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Rawan ShraimDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Laura A VellaDivision of Infectious Diseases, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Josephine R GilesInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Amy E BaxterInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1555-0713
Derek A OldridgeInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Scott W CannaImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Sarah E HenricksonDivision of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Kevin O McNerneyDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Frances BalamuthDivision of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Chakkapong BurudpakdeeDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Jessica LeeDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Tomas LengDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8069-3393
Alvin FarrelDivision of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Michele P LambertImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0439-402X
Kathleen E SullivanImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
E John WherryInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0477-1956
David T Teachey *Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. TEACHEYD@chop.edu.ORCID http://orcid.org/0000-0001-7373-8987
Hamid Bassiri *Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Edward M Behrens *Immune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Children's Hospital of Philadelphia · USTranslational Therapeutics (United States) · US
Funding
Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MImproving risk allocation and developing novel therapies for children with T-ALL and T-LLR01CA193776 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Terzah M Horton, ADAM B OLSHEN · 2015 to 2026
$6.2MCOG NCTN Integrated Translational Science Center for Hematopoietic Malignancies in ChildrenUG1CA233249 · NCI · PUBLIC HEALTH INSTITUTE · PI MESHINCHI, SOHEIL · 2019 to 2025
$4.9MIL-33 Blockade as a Novel Therapeutic for T-cell Mediated Hypercytokinemia SyndromesR01AI121250 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BEHRENS, EDWARD M, KAMBAYASHI, TAKU · 2016 to 2020
$3.0MDiagnosis of MIS-C in febrile childrenR33HD105594 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSIRI, HAMID, ODOM JOHN, AUDREY RAGAN · 2023 to 2023
$2.9MDiagnosis of MIS-C in febrile childrenR61HD105594 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSIRI, HAMID, ODOM JOHN, AUDREY RAGAN · 2021 to 2022
$1.8MUnderstanding Interleukin-18 Mediated Susceptibility to Systemic HyperinflammationR01HD098428 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CANNA, SCOTT WILLIAM · 2019 to 2023
$1.7MCellular and transcriptional control of exhausted CD8 T cells lineage dynamicsR01AI105343 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2014 to 2017
$1.6MTranscriptional and epigenetic regulation of Tfh dysfunction in HIVK08AI136660 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI VELLA, LAURA A · 2018 to 2022
$778kAlex's Lemonade Stand Foundation for Childhood Cancer (Alex's Lemonade Stand Foundation) N/ALeukemia and Lymphoma Society (Leukemia & Lymphoma Society) N/ANCI NIH HHS R01 CA193776NCI NIH HHS T32 CA009140NCI NIH HHS UG1 CA233249NIAID NIH HHS K08 AI136660NIAID NIH HHS R01 AI105343NIAID NIH HHS R01 AI121250NIAID NIH HHS U19 AI082630NICHD NIH HHS R01 HD098428NICHD NIH HHS R33 HD105594NICHD NIH HHS R61 HD105594U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 5UG1CA233249U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA193776U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) X01HD100702-01
Abstract
Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. Here we perform a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesize that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. We show that protein signatures demonstrate overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is an important marker of MIS-C that associates with TMA. We find that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.
Indexed as
ProteomeBiomarkersCase-Control StudiesChemokine CXCL9ChildCOVID-19Endothelium, VascularGroup II Phospholipases A2HumansInflammationInterferon-gammaInterleukin-10ProteomicsSystemic Inflammatory Response SyndromeVascular DiseasesBiomarkersChemokine CXCL9CXCL9 protein, humanGroup II Phospholipases A2IL10 protein, humanInterferon-gammaInterleukin-10PLA2G2A protein, humanProteome
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Registered trials
NCT05576714ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.