ArticleScience immunology2021
Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19.
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Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.
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148citing papers in PubMed, 2 pooled it
37.4field-weighted citation impact, top 1% of its field
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Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis.The American journal of emergency medicine · 2021Pooled it
- The inflammatory markers of multisystem inflammatory syndrome in children (MIS-C) and adolescents associated with COVID-19: A meta-analysis.Journal of medical virology · 2021Pooled it
- Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function.JCI insight · 2026Article
- From hyperinflammation to recovery: serum immune biomarkers predict severity and track rapid inflammatory resolution in MIS-C.Pediatric research · 2026Article
- Screening of autoinflammatory genes in patients with SARS-CoV-2-associated MIS-C.Human genomics · 2026Article
- Shared TCR Vβ21.3+ T cell immunological signature between MIS-A and MIS-C.Journal of human immunity · 2026Article
- Differentiating Multisystem Inflammatory Syndrome in Children (MIS-C) from Acute COVID-19 Using Biomarkers: Toward a Practical Clinical Scoring Model.Biomedicines · 2026Article
- MIS-C: Diagnosis, Management, and Outcomes.Open forum infectious diseases · 2026Review
- How the wild things are: comparative T cell phenotyping and memory T cell identification in wild boar and domestic pigs.Frontiers in immunology · 2026Article
- Association of blood group B and of rare variants affecting immune system with multisystem inflammatory syndrome in children in an Italian cohort.Frontiers in immunology · 2026Article
- Rare Structural Variants Uncovered by Optical Genome Mapping in Multisystem Inflammatory Syndrome in Children (MIS-C).Advanced genetics (Hoboken, N.J.) · 2025Article
- The seven enigmas of SARS-CoV-2: from the past to the future.Journal of human immunity · 2025Article
- Immunological Mechanisms Underlying Allergy Predisposition After SARS-CoV-2 Infection in Children.Cells · 2025Review
- Comparison of Immunomodulatory Therapies for Cardiovascular Clinical and Inflammatory Markers Outcomes in Mild to Moderately Ill Hospitalized Multisystem Inflammatory Syndrome in Children Patients.Journal of cardiovascular development and disease · 2025Article
- SARS-CoV-2 Infection in Children: Revisiting Host-Virus Interactions Through Post-Infection Immune Profiling.Pathogens (Basel, Switzerland) · 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
- Article
- Differentiating Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Using Blood Composite Scores: Insights into Clinical Outcomes and Predictive Indices.Pediatric cardiology · 2025Article
- Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis.Life (Basel, Switzerland) · 2025Review
- SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults' responses.Nature communications · 2025Article
88 more citing papers are in PubMed but not listed here.
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- Update of
Authors and funding
40 authors at 4 institutions in 1 country.
Laura A VellaDivision 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.ORCID 0000-0002-8917-4845
Josephine R GilesInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-3713-338X
Amy E BaxterInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-1555-0713
Derek A OldridgeInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0003-2177-5633
Caroline DiorioImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-8005-3836
Leticia Kuri-CervantesInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-2432-9500
Cécile AlanioInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0003-2785-7445
M Betina PampenaInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0001-6665-4865
Jennifer E WuInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-9302-8904
Zeyu ChenInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Yinghui Jane HuangInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0003-0974-9539
Elizabeth M AndersonInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-1168-4773
Sigrid GoumaInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-7853-8340
Kevin O McNerneyImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-4359-3569
Julie ChaseImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0001-9486-3891
Chakkapong BurudpakdeeImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Jessica H LeeImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Sokratis A ApostolidisInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-0224-0097
Alexander C HuangInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Divij MathewInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-8323-7358
Oliva KuthuruInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-9435-9764
Eileen C GoodwinInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Madison E WeirickInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0003-2112-8102
Marcus J BoltonInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-6933-0548
Claudia P ArevaloInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0003-4062-1605
Andre RamosInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
C J JasenDivision of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,19104, USA.ORCID 0000-0001-9098-467X
Peyton E ConreyDivision of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,19104, USA.ORCID 0000-0001-7766-9878
Samir SayedDivision of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,19104, USA.ORCID 0000-0003-4981-5721
Heather M GianniniDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.ORCID 0000-0002-8979-3806
Kurt D'AndreaDivision of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-7005-3800
UPenn COVID Processing Unit
Nuala J MeyerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.ORCID 0000-0003-4597-5584
Edward M BehrensInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-4603-7963
Hamid BassiriDivision of Infectious Diseases, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0001-6532-8478
Scott E HensleyInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-2928-7506
Sarah E HenricksonInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0001-5569-4132
David T TeacheyImmune Dysregulation Frontier Program, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0001-7373-8987
Michael R BettsInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-7690-1484
E John WherryInstitute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. vellal@chop.edu wherry@pennmedicine.upenn.edu.ORCID 0000-0003-0477-1956
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · USTranslational Therapeutics (United States) · USParker Institute for Cancer Immunotherapy · US
Funding
Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG, GEORG Michael LAUER · 2009 to 2026
$48.1MPenn integrated Human Pancreas procurement and Analysis ProgramUC4DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI BETTS, MICHAEL R, FELDMAN, MICHAEL D · 2016 to 2020
$17.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MTRAINING IN PULMONARY IMMUNOLOGYT32HL007586 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 1985 to 2025
$8.8MTRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8MImproving 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
$6.2MIL-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
$3.0MTargeting Angiopoietin-2 in ARDSR01HL137006 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 2017 to 2021
$2.5MReconsidering the IL-1 axis in sepsis-associated ARDSR01HL137915 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MEYER, NUALA JENNINGS · 2017 to 2020
$2.1MDiagnosis of MIS-C in febrile childrenR61HD105594 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSIRI, HAMID, ODOM JOHN, AUDREY RAGAN · 2021 to 2022
$1.8MCellular and transcriptional control of exhausted CD8 T cells lineage dynamicsR01AI105343 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2014 to 2017
$1.6MThe Penn-StARR Program for Research in ResidencyR38HL143613 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KLEIN, PETER S · 2018 to 2021
$1.4MNCI NIH HHS F99 CA234842NCI NIH HHS K00 CA234842NCI NIH HHS K08 CA230157NCI NIH HHS R01 CA193776NCI NIH HHS T32 CA009140NHLBI NIH HHS R01 HL137006NHLBI NIH HHS R01 HL137915NHLBI NIH HHS R38 HL143613NHLBI NIH HHS T32 HL007586NIAID NIH HHS K08 AI135091NIAID NIH HHS K08 AI136660NIAID NIH HHS R01 AI105343NIAID NIH HHS R01 AI121250NIAID NIH HHS T32 AI007324NIAID NIH HHS U19 AI082630NICHD NIH HHS R61 HD105594NIH HHS AI082630NIH HHS AI105343NIH HHS CA230157NIH HHS HL137006NIH HHS HL137915NIH HHS HL143613Wellcome Trust
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.
Indexed as
Lymphocyte ActivationAdolescentAdultAgingChildChild, PreschoolCOVID-19FemaleFlow CytometryHumansLeukopeniaMaleSystemic Inflammatory Response SyndromeT-LymphocytesYoung Adult
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