{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:58:39Z","timestamp":1793393919042,"version":"4.5.0"},"reference-count":14,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006418","name":"Brown University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54GM115677"],"award-info":[{"award-number":["U54GM115677"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Although the range of immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is variable, cytokine storm is observed in a subset of symptomatic individuals. To further understand the disease pathogenesis and, consequently, to develop an additional tool for clinicians to evaluate patients for presumptive intervention, we sought to compare plasma cytokine levels between a range of donor and patient samples grouped by a COVID-19 Severity Score (CSS) based on the need for hospitalization and oxygen requirement. Here we utilize a mutual information algorithm that classifies the information gain for CSS prediction provided by cytokine expression levels and clinical variables. Using this methodology, we found that a small number of clinical and cytokine expression variables are predictive of presenting COVID-19 disease severity, raising questions about the mechanism by which COVID-19 creates severe illness. The variables that were the most predictive of CSS included clinical variables such as age and abnormal chest x-ray as well as cytokines such as macrophage colony-stimulating factor, interferon-inducible protein 10, and interleukin-1 receptor antagonist. Our results suggest that SARS-CoV-2 infection causes a plethora of changes in cytokine profiles and that particularly in severely ill patients, these changes are consistent with the presence of macrophage activation syndrome and could furthermore be used as a biomarker to predict disease severity.<\/jats:p>","DOI":"10.7554\/elife.64958","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T08:05:00Z","timestamp":1610611500000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.64958","source":"Crossref","is-referenced-by-count":27,"title":["Cytokine ranking via mutual information algorithm correlates cytokine profiles with presenting disease severity in patients infected with SARS-CoV-2"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5810-8220","authenticated-orcid":true,"given":"Kelsey E","family":"Huntington","sequence":"first","affiliation":[{"name":"Brown Experimentalists Against COVID-19 (BEACON) Group, Brown University, Providence, United States"},{"name":"Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, United States"},{"name":"Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-6106","authenticated-orcid":true,"given":"Anna D","family":"Louie","sequence":"additional","affiliation":[{"name":"Brown Experimentalists Against COVID-19 (BEACON) Group, Brown University, Providence, United States"},{"name":"Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, United States"},{"name":"Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"Department of Surgery, Lifespan Health System and Warren Alpert Medical School, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, United States"},{"name":"Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A","family":"Elias","sequence":"additional","affiliation":[{"name":"The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, United States"},{"name":"Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"Department of Molecular Microbiology and Immunology, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A","family":"Ross","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Temple University Health System, Philadelphia, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-8266","authenticated-orcid":true,"given":"Wafik S","family":"El-Deiry","sequence":"additional","affiliation":[{"name":"Brown Experimentalists Against COVID-19 (BEACON) Group, Brown University, Providence, United States"},{"name":"Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"The Joint Program in Cancer Biology, Brown University and Lifespan Health System, Providence, United States"},{"name":"Cancer Center at Brown University, Warren Alpert Medical School, Brown University, Providence, United States"},{"name":"Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"bib1","article-title":"Varrank: an R package for variable ranking based on mutual information with applications to observed systemic datasets.\u00a0","volume-title":"arXiv","author":"Kratzer","year":"2018","unstructured":"Kratzer G, Furrer R. 2018. Varrank: an R package for variable ranking based on mutual information with applications to observed systemic datasets.\u00a0. arXiv. http:\/\/arxiv.org\/abs\/1804.07134."},{"key":"bib2","article-title":"Varrank","volume-title":"Heuristics Tools Based on Mutual Information for Variable Ranking","author":"Kratzer","year":"2020","unstructured":"Kratzer G, Furrer R. 2020. Varrank. Heuristics Tools Based on Mutual Information for Variable Ranking. 0.3. https:\/\/CRAN.R-project.org\/package=varrank."},{"key":"bib3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.cytogfr.2011.06.001","article-title":"CXCL10\/IP-10 in infectious diseases pathogenesis and potential therapeutic implications","volume":"22","author":"Liu","year":"2011","journal-title":"Cytokine & Growth Factor Reviews"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102537","article-title":"The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation Syndrome-Like disease","volume":"19","author":"McGonagle","year":"2020","journal-title":"Autoimmunity Reviews"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nature Reviews Immunology"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-020-00131-w","article-title":"Macrophage activation syndrome and COVID-19","volume":"40","author":"Otsuka","year":"2020","journal-title":"Inflammation and Regeneration"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd5487","article-title":"Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients","volume":"12","author":"Pierce","year":"2020","journal-title":"Science Translational Medicine"},{"key":"bib8","article-title":"R: A Language and Environment for Statistical Computing","author":"R Development Core Team","year":"2020","unstructured":"R Development Core Team. 2020. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. https:\/\/www.r-project.org\/."},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 cytokine storm; What we know so far","volume":"11","author":"Ragab","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"bib10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01708","article-title":"Cytokine storm in COVID-19: the current evidence and treatment strategies","volume":"11","author":"Tang","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in hospitalized patients with Covid-19 \u2014 Preliminary Report","volume":"17","author":"The RECOVERY Collaborative Group","year":"2020","journal-title":"The New England Journal of Medicine"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1101\/2020.02.10.20021832","article-title":"Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)","volume-title":"medRxiv","author":"Wan","year":"2020"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"4201","DOI":"10.18632\/oncotarget.27799","article-title":"MEK inhibitors reduce cellular expression of ACE2, pERK, pRb while stimulating NK-mediated cytotoxicity and attenuating inflammatory cytokines relevant to SARS-CoV-2 infection","volume":"11","author":"Zhou","year":"2020","journal-title":"Oncotarget"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"New England Journal of Medicine"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64958\/elife-64958-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/64958\/elife-64958-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/64958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:07:36Z","timestamp":1697058456000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/64958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":14,"alternative-id":["10.7554\/eLife.64958"],"URL":"https:\/\/doi.org\/10.7554\/elife.64958","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.11.24.20235721","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.64958.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.64958.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"article-number":"e64958"}}