Dataset Information

Distinct Cytokine and Chemokine Dysregulation in Hospitalized Children With Acute Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome With Similar Levels of Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 Shedding.

ABSTRACT:

Background

Multisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood.

Methods

Hospitalized children <18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex.

Results

The median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5-13.9) and 2.2 years (IQR, 1.1-10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL]-1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP]-1α, MCP-2, MIP-1β, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate <0.05; P < .05).

Conclusions

The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.

SUBMITTER: Peart Akindele N

PROVIDER: S-EPMC8241418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe 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.MethodsCase 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.ResultsMEDLINE 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.ConclusionsMIS-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.