Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.

Autor: Schimke LF; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Marques AHC; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Baiocchi GC; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., de Souza Prado CA; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Fonseca DLM; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Freire PP; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Rodrigues Plaça D; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Salerno Filgueiras I; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Coelho Salgado R; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Jansen-Marques G; Information Systems, School of Arts, Sciences and Humanities, University of Sao Paulo, São Paulo 03828-000, Brazil., Rocha Oliveira AE; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Peron JPS; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Cabral-Miranda G; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Barbuto JAM; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.; Laboratory of Medical Investigation in Pathogenesis, Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil., Camara NOS; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Calich VLG; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Ochs HD; Department of Pediatrics, Seattle Children's Research Institute, University of Washington School of Medicine, Seattle, WA 98101, USA., Condino-Neto A; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil., Overmyer KA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA.; Morgridge Institute for Research, Madison, WI 53562, USA., Coon JJ; National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA.; Morgridge Institute for Research, Madison, WI 53562, USA.; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53506, USA.; Department of Chemistry, University of Wisconsin, Madison, WI 53506, USA., Balnis J; Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA.; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Jaitovich A; Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA.; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA., Schulte-Schrepping J; Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany., Ulas T; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, University of Bonn, 53127 Bonn, Germany., Schultze JL; Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Bonn, 53127 Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, University of Bonn, 53127 Bonn, Germany., Nakaya HI; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.; Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil.; Scientific Platform Pasteur, University of São Paulo, São Paulo 05508-020, Brazil., Jurisica I; 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.; Departments of Medical Biophysics and Computer Science, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1L7, Canada.; Institute of Neuroimmunology, Slovak Academy of Sciences, 845 10 Bratislava, Slovakia., Cabral-Marques O; Department of Imunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.; Network of Immunity in Infection, Malignancy, Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo 05508-000, Brazil.
Jazyk: angličtina
Zdroj: Cells [Cells] 2022 Mar 01; Vol. 11 (5). Date of Electronic Publication: 2022 Mar 01.
DOI: 10.3390/cells11050847
Abstrakt: 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.
Databáze: MEDLINE
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