{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:37:43Z","timestamp":1790019463923,"version":"4.0.1"},"reference-count":125,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Latin American Society of Immunodeficiencies","award":["LASID Fellowship award 2020"],"award-info":[{"award-number":["LASID Fellowship award 2020"]}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2018\/18886-9, 2020\/01688-0, and 2020\/07069-0"],"award-info":[{"award-number":["2018\/18886-9, 2020\/01688-0, and 2020\/07069-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ontario Research Fund","award":["#34876"],"award-info":[{"award-number":["#34876"]}]},{"name":"Natural Sciences Research Council","award":["#203475"],"award-info":[{"award-number":["#203475"]}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["#29272, #225404, #33536"],"award-info":[{"award-number":["#29272, #225404, #33536"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL130704, HL160661, P41 GM108538"],"award-info":[{"award-number":["HL130704, HL160661, P41 GM108538"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine\/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.<\/jats:p>","DOI":"10.3390\/cells11050847","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T08:17:03Z","timestamp":1646122623000},"page":"847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5616-3410","authenticated-orcid":false,"given":"Lena F.","family":"Schimke","sequence":"first","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre H. C.","family":"Marques","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0246-5883","authenticated-orcid":false,"given":"Gabriela Crispim","family":"Baiocchi","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-6303","authenticated-orcid":false,"given":"Caroline Aliane","family":"de Souza Prado","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennyson Leandro M.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0649-8279","authenticated-orcid":false,"given":"Paula Paccielli","family":"Freire","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desir\u00e9e","family":"Rodrigues Pla\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-4464","authenticated-orcid":false,"given":"Igor","family":"Salerno Filgueiras","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-9747","authenticated-orcid":false,"given":"Ranieri","family":"Coelho Salgado","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Jansen-Marques","sequence":"additional","affiliation":[{"name":"Information Systems, School of Arts, Sciences and Humanities, University of Sao Paulo, S\u00e3o Paulo 03828-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Edson","family":"Rocha Oliveira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1638-8866","authenticated-orcid":false,"given":"Jean Pierre Schatzmann","family":"Peron","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Cabral-Miranda","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, 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NY 12208, USA"},{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Jaitovich","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA"},{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Schulte-Schrepping","sequence":"additional","affiliation":[{"name":"Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany"},{"name":"Systems Medicine, Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ulas","sequence":"additional","affiliation":[{"name":"Systems Medicine, Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim L.","family":"Schultze","sequence":"additional","affiliation":[{"name":"Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany"},{"name":"Systems Medicine, Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder I.","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05652-900, Brazil"},{"name":"Scientific Platform Pasteur, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-946X","authenticated-orcid":false,"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[{"name":"Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, Canada"},{"name":"Departments of Medical Biophysics and Computer Science, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1L7, Canada"},{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ot\u00e1vio","family":"Cabral-Marques","sequence":"additional","affiliation":[{"name":"Department of Imunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Network of Immunity in Infection, Malignancy, Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and 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