TY - JOUR
T1 - 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
AU - Peart Akindele, Nadine
AU - Kouo, Theodore
AU - Karaba, Andrew H.
AU - Gordon, Oren
AU - Fenstermacher, Katherine Z.J.
AU - Beaudry, Jeanette
AU - Rubens, Jessica H.
AU - Atik, Christine C.
AU - Zhou, Weiqiang
AU - Ji, Hongkai
AU - Tao, Xueting
AU - Vaidya, Dhananjay
AU - Mostafa, Heba
AU - Caturegli, Patrizio
AU - Blair, Paul W.
AU - Sauer, Lauren
AU - Cox, Andrea L.
AU - Persaud, Deborah
N1 - Funding Information:
This work is funded by the National Institutes of Health (NIH) (Grant Number NIH5T32AI052071; to N. P. A. and J. H. R.); NIH Grant Numbers 5T32HD044355-17 (to T. K.), R01HG009518 (to W. Z. and H. J.), UM1AI0686, UM1 AI068613-14, R01 DA045556-04S1, and 3U54HL143541-02S2 (to H. M.); The Bauernschmidt Committee of the Eudowood Board at Johns Hopkins School of Medicine (to N. P. A.); The Johns Hopkins University Center for AIDS Research (Grant Number P30AI094189; to D. P.); the International Maternal Pediatric Adolescent Clinical Trials Laboratory Center (Grant Number UM1AI106716; to D. P.); the Bill & Melinda Gates Foundation (Grant Number 134582; to A. L. C.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Grant Number K12-HD000850; to J. H. R.); and also supported by a Johns Hopkins University Provost Research Grant.
Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PY - 2021/8/15
Y1 - 2021/8/15
N2 - 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.
AB - 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.
KW - COVID-19
KW - MIS-C
KW - SARS-CoV-2
KW - coronavirus
KW - viral RNA
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U2 - 10.1093/infdis/jiab285
DO - 10.1093/infdis/jiab285
M3 - Article
C2 - 34398245
AN - SCOPUS:85111338707
SN - 0022-1899
VL - 224
SP - 606
EP - 615
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -