ArticleNature medicine2022
Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Nature medicine, 2022. 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 158 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed, 4 pooled it
52.7field-weighted citation impact, top 1% of its field
What it found
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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
158 citing papers in PubMed, 4 syntheses or guidelines pooled it, 249 citations in OpenAlex.
- Long-Term Complications of Multisystem Inflammatory Syndrome in Children and Adults Post-COVID-19: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Multi-omics time-series analysis in microbiome research: a systematic review.Briefings in bioinformatics · 2025Pooled it
- Early peripheral blood MCEMP1 and HLA-DRA expression predicts COVID-19 prognosis.EBioMedicine · 2023Pooled it
- Safety of COVID-19 Pfizer-BioNtech (BNT162b2) mRNA vaccination in adolescents aged 12-17 years: A systematic review and meta-analysis.Human vaccines & immunotherapeutics · 2022Pooled it
- Autoantibody-Based Models for the Diagnosis and Activity Assessment of Takayasu Arteritis.Journal of cardiovascular translational research · 2026Article
- A pre-trained large generative model for translating single-cell transcriptomes to proteomes.Nature biomedical engineering · 2026Article
- From hyperinflammation to recovery: serum immune biomarkers predict severity and track rapid inflammatory resolution in MIS-C.Pediatric research · 2026Article
- Tracking the soluble biomarkers of MIS-C and their association with clinical parameters and severity.Pediatric research · 2026Article
- SARS-CoV-2 infection and vaccination elicit distinct pharyngeal mucosal B cell responses in children.Nature communications · 2026Article
- A longitudinal comparative analysis of serum metabolomic signatures in children with SARS-CoV-2 infection and MIS-C.Communications medicine · 2026Article
- The Effect of Low Socioeconomic Status on the Leptin-to-Adiponectin Ratio.Nursing open · 2026Review
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) from Acute COVID-19 Using Biomarkers: Toward a Practical Clinical Scoring Model.Biomedicines · 2026Article
- Ozone exposure is positively correlated with the occurrence of Kawasaki disease in Chinese children.Pediatric research · 2026Article
- Cytokine and Whole-Genome Sequence Analysis in Korean Patients With Multisystem Inflammatory Syndrome in Children.Journal of Korean medical science · 2025Article
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- Mass spectrometry combined with machine learning identifies novel protein signatures as demonstrated with multisystem inflammatory syndrome in children.Scientific reports · 2025Article
- Polyclonal Vβ21.3 expansion in multisystem inflammatory syndrome in children despite SARS-CoV-2 vaccination.RMD open · 2025Article
- Immunological Mechanisms Underlying Allergy Predisposition After SARS-CoV-2 Infection in Children.Cells · 2025Review
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
65 authors at 18 institutions in 6 countries.
Keith Sacco *Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8189-7769
Riccardo Castagnoli *Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0029-9383
Svetlana Vakkilainen *Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Can Liu *Multiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8411-3891
Ottavia M DelmonteLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Cihan OguzNIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ian M KaplanAdaptive Biotechnologies, Seattle, WA, USA.
Sara AlehashemiLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6531-6108
Peter D BurbeloNational Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Farzana BhuyanLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Adriana A de JesusLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kerry DobbsLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3432-3137
Lindsey B RosenLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Aristine ChengLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Elana ShawLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Mikko S VakkilainenDepartment of Computer Science, Aalto University, Helsinki, Finland.
Francesca PalaLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4537-9061
Justin LackMultiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Yu ZhangLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Danielle L FinkApplied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Vasileios OikonomouLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7553-0159
Andrew L SnowDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8728-6691
Clifton L DalgardDepartment of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2025-8239
Jinguo ChenTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.
Brian A SellersTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation (CHI), National Institutes of Health, Bethesda, MD, USA.
Gina A Montealegre SanchezIntramural Clinical Management and Operation Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Karyl BarronDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Emma Rey-JuradoFacultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
Cecilia VialFacultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.ORCID http://orcid.org/0000-0002-0399-6144
Maria Cecilia PoliFacultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.ORCID http://orcid.org/0000-0001-6817-0573
Amelia LicariPediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Daniela MontagnaPediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Gian Luigi MarsegliaPediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Francesco LicciardiDepartment 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.
Ugo RamenghiDepartment 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.
Valentina DiscepoloDepartment of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
Andrea Lo VecchioDepartment of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
Alfredo GuarinoDepartment of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Napoli, Italy.
Eli M EisensteinDepartment of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel.
Luisa ImbertiCREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.ORCID http://orcid.org/0000-0002-2075-8391
Alessandra SottiniCREA Laboratory (AIL Center for Hemato-Oncologic Research), Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.ORCID http://orcid.org/0000-0001-5404-228X
Andrea BiondiPediatric Department and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN, University of Milano Bicocca, Fondazione MBBM, Ospedale San Gerardo, Monza, Italy.
Sayonara MatóRandall Children's Hospital at Legacy Emanuel, Portland, OR, USA.
Dana GerstbacherDivision of Pediatric Rheumatology, Stanford Children's Hospital, Stanford, CA, USA.
Meng TruongLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Michael A StackLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Mary MaglioccoMolecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Marita BosticardoLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1771-4523
Tomoki KawaiLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jeffrey J DanielsonLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Tyler HulettCDI Laboratories, Antygen Division, Baltimore, MD, USA.
Manor AskenaziCDI Laboratories, Antygen Division, Baltimore, MD, USA.
Shaohui HuCDI Laboratories, Antygen Division, Baltimore, MD, USA.
NIAID Immune Response to COVID Group
Chile MIS-C Group
Pavia Pediatric COVID-19 Group
Jeffrey I CohenLaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Helen C SuLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5582-9110
Douglas B KuhnsApplied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Michail S LionakisLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4994-9500
Thomas M SnyderAdaptive Biotechnologies, Seattle, WA, USA.
Steven M HollandLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3207-5464
Raphaela Goldbach-ManskyLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
John S TsangMultiscale Systems Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3186-3047
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. luigi.notarangelo2@nih.gov.ORCID http://orcid.org/0000-0002-8335-0262
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USUniversity of Pavia · ITHospital Roberto del Rio · CLCDI Laboratories (United States) · PRUniversidad del Desarrollo · CLUniversity of Naples Federico II · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITOspedale Regina Margherita · ITUniformed Services University of the Health Sciences · USAalto University · FIAdaptive Biotechnologies (United States) · USFrederick National Laboratory for Cancer Research · USHadassah Medical Center · ILLeidos (United States) · USLucile Packard Children's Hospital · USRandall Children's Hospital at Legacy Emanuel · USUniversity of Milano-Bicocca · IT
Funding
WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6MInfectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1MCenter for Human Immunology ZICAI001226 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2018 to 2025
$34.1MPathogenesis, and Outcome of Autoinflammatory Diseases, NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Stills-like Diseases, and other Undifferentiated Autoinflammatory DiseasesZIAAI001220 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI GOLDBACH-MANSKY, RAPHAELA · 2017 to 2025
$22.3MIntegrative analysis and modeling of human immune responses and pathologiesZIAAI001152 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TSANG, JOHN · 2011 to 2022
$14.1MHost factors contributing to susceptibility to COVID-19 diseaseZIAAI001265 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN CHUN-HUI · 2020 to 2025
$9.5MImmune response to COVID-19 vaccination in individuals with immune disordersZIAAI001335 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RICOTTA, EMILY · 2021 to 2024
$1.8MSystems Immunology of COVID-19ZIAAI001266 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TSANG, JOHN · 2020 to 2022
$1.2MCharacterization of host immune responses to SARS-CoV-2ZIAAI001270 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2020 to 2025
$1.2MSerologic studies of persons with COVID-19 infectionZIAAI001258 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI COHEN, JEFFREY · 2020 to 2025
$411kThe pathogenesis of COVID-19ZIAAI001318 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LIONAKIS, MICHAIL · 2020 to 2023
$290kAnticytokine Autoantibodies in COVID-19ZIAAI001312 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2020 to 2024
$140kIntramural NIH HHS ZIA AI001265Intramural NIH HHS ZIA AI001270NCI NIH HHS 75N91019D00024
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.
Indexed as
COVID-19ChildHumansSARS-CoV-2Systemic Inflammatory Response SyndromeT-Lymphocytes
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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.