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The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children: A Systematic Review
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Background: The clinical manifestations and natural history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related multisystem inflammatory syndrome in children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C. Methods: Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search, and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion. Results: MEDLINE and EMBASE searches produced 129 articles, and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty-two children (14.7%) had negative results for SARS-CoV-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), cheilitis/ “strawberry tongue” (55.7%), or extremity edema/erythema (47.5%). Median serum C-reactive protein, ferritin, fibrinogen, and D-dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone (57.6%) were the most common therapeutic interventions; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%), but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died. Conclusions: MIS-C following SARS-CoV-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, cheilitis, and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.
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Multisystem inflammatory syndrome in children associated with SARS-CoV-2 is an example of how disease expression of COVID-19 is tied to maturational state.
“The emergence of the multisystem inflammatory syndrome in children associated with SARS-CoV-2 (ref. 24) is an example of how disease expression of COVID-19 is tied to maturational state.”
From SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges (2021) · cites this paper as [24]
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Metadata
- Authors
- Aronoff, S. C., Hall, A., & Del Vecchio, M. T.
- Affiliations
- St. Christopher's Hospital for Children (US)
- Temple University (US)
- Department of Pediatrics, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA
- Corresponding author
- Aronoff, Stephen C
- Venue
- Journal of the Pediatric Infectious Diseases Society
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-09-14
- Volume
- 9
- Issue
- 6
- Pages
- 746-751
- ISSN
- 2048-7193 (ISSN-L)
- 2048-7207
- PMC
- PMC7797745
- OpenAlex
- W3085761938
- Cited by
- 78
- References
- 24
- Citations by year
- 2025: 1 · 2024: 7 · 2023: 13 · 2022: 22 · 2021: 32 · 2020: 3
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of the Pediatric Infectious Diseases Society (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Kawasaki Disease and Coronary Complications
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- multisystem inflammatory syndrome in children, SARS-CoV-2, COVID-19 pandemic, natural history (disease), clinical features, cardiac dysfunction, organ dysfunction, intravenous immunoglobulin, corticosteroids, immunomodulation, anticoagulation, thrombotic complications, acute kidney injury, extracorporeal membrane oxygenation, pediatric patients, case series
- MeSH terms
- COVID-19, Acute Disease, Child, Humans, Systemic Inflammatory Response Syndrome
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