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.
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.
['Peart Akindele|Nadine|N|0000-0001-8697-0240', 'Kouo|Theodore|T|', 'Karaba|Andrew H|AH|', 'Gordon|Oren|O|', 'Fenstermacher|Katherine Z J|KZJ|', 'Beaudry|Jeanette|J|', 'Rubens|Jessica H|JH|', 'Atik|Christine C|CC|', 'Zhou|Weiqiang|W|', 'Ji|Hongkai|H|', 'Tao|Xueting|X|', 'Vaidya|Dhananjay|D|', 'Mostafa|Heba|H|', 'Caturegli|Patrizio|P|', 'Blair|Paul W|PW|', 'Sauer|Lauren|L|', 'Cox|Andrea L|AL|', 'Persaud|Deborah|D|']
D000293:Adolescent D000367:Age Factors D000914:Antibodies, Viral D015415:Biomarkers D000086382:COVID-19 D018925:Chemokines D002648:Child D002675:Child, Preschool D016207:Cytokines D054884:Host-Pathogen Interactions D006801:Humans D008297:Male D012367:RNA, Viral D000086402:SARS-CoV-2 D012698:Serologic Tests D012720:Severity of Illness Index D012737:Sex Factors D018746:Systemic Inflammatory Response Syndrome D019562:Viral Load
coronavirus MIS-C SARS-CoV-2 COVID-19 viral RNA