86d0388d387fb8e1fa15b9305ebd745a 309006.pdf 566f2e286e1ff2023cc1509d3a5cb267cf2e2ac6 309006.pdf 930c65877f5ae5d2adc7ec3006e85d460bbf0f9f6912bf781efa867e5524d539 309006.pdf Title: The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease Subject: Purpose: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease. Results: Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease. Keywords: cancer; COVID-19; dNLR; neutrophils; IL-6 Author: Elia Seguí, Juan Manuel Torres, Edouard Auclin, David Casadevall, Sara Peiro Carmona, Juan Aguilar-Company, Marta García de Herreros, Teresa Gorría, Juan Carlos Laguna, Marta Rodríguez, Azucena González, Nicolas Epaillard, Javier Gavira, Victor Bolaño, Jose C. Tapia, Marco Tagliamento, Cristina Teixidó, Hugo Arasanz, Sara Pilotto, Rafael Lopez-Castro, Xabier Mielgo-Rubio, Cristina Urbano, Gonzalo Recondo, Mar Diaz Pavon, Maria Virginia Bluthgen, José Nicolas Minatta, Lorena Lupinacci, Fara Brasó-Maristany, Aleix Prat, Alexandru Vlagea and Laura Mezquita Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Aug 27 12:11:03 2024 CEST ModDate: Tue Aug 27 12:17:41 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2607446 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 YBVJTP+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 HDEFFY+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 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DJIJPO+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 262 0 DJIJPP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 268 0 DJIKAA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 271 0 DJIKAB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 274 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-03-19 02:42:14 CET RepresentationInformation: 309006.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-03-18 13:54:43 CET Size: 2607446 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 464 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Children: Item: Title: Study Design, Study Population, and Data Collection Destination: subsection.2.1 Children: Item: Title: Retrospective Clinical Cohort Destination: subsubsection.2.1.1 Item: Title: Prospective Exploratory Cohort Destination: subsubsection.2.1.2 Item: Title: Data Collection Destination: subsubsection.2.1.3 Item: Title: Endpoints Destination: subsection.2.2 Item: Title: Immunophenotyping Destination: subsection.2.3 Item: Title: Serum Analyses Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Study Population Destination: subsection.3.1 Children: Item: Title: Retrospective Clinical Cohort Destination: subsubsection.3.1.1 Item: Title: Prospective Exploratory Cohort Destination: subsubsection.3.1.2 Item: Title: dNLR in Patients with Cancer and COVID-19 Infection Destination: subsection.3.2 Item: Title: Building of the FLARE Score Destination: subsection.3.3 Item: Title: The FLARE Score Is Correlated with Early Mortality Destination: subsection.3.4 Item: Title: Circulating Neutrophils in Patients with Cancer and COVID-19 Infection Destination: subsection.3.5 Item: Title: Circulating Immature Neutrophils in Patients with Cancer and COVID-19 Infection Destination: subsection.3.6 Item: Title: Correlation between Circulating Inflammatory Cytokines, Circulating Immature Neutrophils, and Circulating Inflammatory Markers (dNLR) in Patients with Cancer and COVID-19 Infection Destination: subsection.3.7 Item: Title: Monitoring of Circulating Neutrophils and IL-6 Destination: subsection.3.8 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease Author: Elia Seguí, Juan Manuel Torres, Edouard Auclin, David Casadevall, Sara Peiro Carmona, Juan Aguilar-Company, Marta García de Herreros, Teresa Gorría, Juan Carlos Laguna, Marta Rodríguez, Azucena González, Nicolas Epaillard, Javier Gavira, Victor Bolaño, Jose C. Tapia, Marco Tagliamento, Cristina Teixidó, Hugo Arasanz, Sara Pilotto, Rafael Lopez-Castro, Xabier Mielgo-Rubio, Cristina Urbano, Gonzalo Recondo, Mar Diaz Pavon, Maria Virginia Bluthgen, José Nicolas Minatta, Lorena Lupinacci, Fara Brasó-Maristany, Aleix Prat, Alexandru Vlagea and Laura Mezquita Subject: Purpose: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease. Results: Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease. 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