{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:50:47Z","timestamp":1768564247538,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,4]]},"group-title":"Pediatrics","reference-count":30,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>An objective method to identify imminent or current Multi-Inflammatory Syndrome in Children (MIS-C) infected with SARS-CoV-2 is highly desirable. The aims was to define an algorithmically interpreted novel cytokine\/chemokine assay panel providing such an objective classification. This study was conducted on 4 groups of patients seen at multiple sites of Texas Children\u2019s Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine\/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 66 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January-May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August-October 2021 infected with alpha and\/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021-January 2022 infected with delta and\/or omicron variants. Group 1 was used to train a L1-regularized logistic regression model which was validated using 5-fold cross validation, and then separately validated against the remaining na\u00efve groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the algorithmically interpreted cytokine\/chemokine assay panel. Standard laboratory markers predict MIS-C with a 5-fold cross-validated AUROC of 0.86 \u00b1 0.05 and an F1 score of 0.78 \u00b1 0.07, while the cytokine\/chemokine panel predicted MIS-C with a 5-fold cross-validated AUROC of 0.95 \u00b1 0.02 and an F1 score of 0.91 \u00b1 0.04, with only sixteen of the forty-five cytokines\/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine\/chemokine panel yielded AUROC =0.98, F1=0.93, on Group 3 it yielded AUROC=0.89, F1 = 0.89, and on Group 4 AUROC= 0.99, F1= 0.97). Adding standard laboratory markers to the cytokine\/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieves equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine\/chemokine panel as well as the top ten subset provides a sensitive, specific method to identify MIS-C in patients infected with SARS-CoV-2 of all the major variants identified to date.<\/jats:p>","DOI":"10.1101\/2023.04.04.23288117","type":"posted-content","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T17:50:11Z","timestamp":1680630611000},"source":"Crossref","is-referenced-by-count":1,"title":["Stratification of Pediatric COVID-19 cases by inflammatory biomarker profiling and machine learning"],"prefix":"10.64898","author":[{"given":"Devika","family":"Subramanian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aadith","family":"Vittala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinpu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Julien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Rusin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl","family":"Allen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Rider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zbigniew","family":"Starosolski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananth","family":"Annapragada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridevi","family":"Devaraj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"9","key":"2023040704150485000_2023.04.04.23288117v1.1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1001\/jamapediatrics.2020.1467","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review","volume":"174","year":"2020","journal-title":"JAMA Pediatr"},{"issue":"22","key":"2023040704150485000_2023.04.04.23288117v1.2","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1016\/j.vaccine.2021.01.054","article-title":"Multisystem inflammatory syndrome in children and adults (MIS-C\/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data","volume":"39","year":"2021","journal-title":"Vaccine"},{"issue":"2","key":"2023040704150485000_2023.04.04.23288117v1.3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3345\/cep.2020.01900","article-title":"Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019","volume":"64","year":"2021","journal-title":"Clin Exp Pediatr"},{"key":"2023040704150485000_2023.04.04.23288117v1.4","doi-asserted-by":"publisher","DOI":"10.100\/jama.2020.10369"},{"issue":"6","key":"2023040704150485000_2023.04.04.23288117v1.5","doi-asserted-by":"crossref","first-page":"e0253894","DOI":"10.1371\/journal.pone.0253894","article-title":"Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis","volume":"16","year":"2021","journal-title":"PLoS One"},{"issue":"11","key":"2023040704150485000_2023.04.04.23288117v1.6","first-page":"e14450","article-title":"Multisystem inflammatory syndrome in children (MISC): a systematic review","volume":"75","year":"2021","journal-title":"Int J Clin Pract"},{"issue":"1","key":"2023040704150485000_2023.04.04.23288117v1.7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","article-title":"Regression shrinkage and selection via the lasso","volume":"58","year":"1996","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"2023040704150485000_2023.04.04.23288117v1.8","doi-asserted-by":"crossref","unstructured":"Ng AY. 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