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An immune-based biomarker signature is associated with mortality in COVID-19 patients.
Abers, Michael S; Delmonte, Ottavia M; Ricotta, Emily E; Fintzi, Jonathan; Fink, Danielle L; de Jesus, Adriana A Almeida; Zarember, Kol A; Alehashemi, Sara; Oikonomou, Vasileios; Desai, Jigar V; Canna, Scott W; Shakoory, Bita; Dobbs, Kerry; Imberti, Luisa; Sottini, Alessandra; Quiros-Roldan, Eugenia; Castelli, Francesco; Rossi, Camillo; Brugnoni, Duilio; Biondi, Andrea; Bettini, Laura Rachele; D'Angio', Mariella; Bonfanti, Paolo; Castagnoli, Riccardo; Montagna, Daniela; Licari, Amelia; Marseglia, Gian Luigi; Gliniewicz, Emily F; Shaw, Elana; Kahle, Dana E; Rastegar, Andre T; Stack, Michael; Myint-Hpu, Katherine; Levinson, Susan L; DiNubile, Mark J; Chertow, Daniel W; Burbelo, Peter D; Cohen, Jeffrey I; Calvo, Katherine R; Tsang, John S; Su, Helen C; Gallin, John I; Kuhns, Douglas B; Goldbach-Mansky, Raphaela; Lionakis, Michail S; Notarangelo, Luigi D.
  • Abers MS; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Delmonte OM; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Ricotta EE; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Fintzi J; Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, USA.
  • Fink DL; Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • de Jesus AAA; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Zarember KA; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Alehashemi S; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Oikonomou V; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Desai JV; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Canna SW; Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Shakoory B; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Dobbs K; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Imberti L; CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Sottini A; CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy.
  • Quiros-Roldan E; Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
  • Castelli F; Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy.
  • Rossi C; Direzione Sanitaria, ASST Spedali Civili di Brescia, Italy.
  • Brugnoni D; Laboratorio Analisi Chimico-Cliniche, ASST Spedali Civili, Brescia, Italy.
  • Biondi A; Pediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
  • Bettini LR; Pediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
  • D'Angio' M; Pediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders-University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
  • Bonfanti P; Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
  • Castagnoli R; Department of Pediatrics and.
  • Montagna D; Laboratory of Immunology and Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Licari A; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Marseglia GL; Department of Pediatrics and.
  • Gliniewicz EF; Department of Pediatrics and.
  • Shaw E; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Kahle DE; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Rastegar AT; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Stack M; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Myint-Hpu K; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Levinson SL; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • DiNubile MJ; BioAegis Therapeutics, Inc, North Brunswick, New Jersey, USA.
  • Chertow DW; BioAegis Therapeutics, Inc, North Brunswick, New Jersey, USA.
  • Burbelo PD; Critical Care Medicine Department, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
  • Cohen JI; National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
  • Calvo KR; Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
  • Tsang JS; Hematology Section, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
  • Su HC; Center for Human Immunology, Autoimmunity, and Inflammation, NIAID, NIH, Bethesda, Maryland, USA.
  • Kuhns DB; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Goldbach-Mansky R; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
  • Lionakis MS; Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
JCI Insight ; 6(1)2021 01 11.
Article in English | MEDLINE | ID: covidwho-1027164
Semantic information from SemMedBD (by NLM)
1. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
2. NF-kappa B AUGMENTS Transcriptio
Subject
NF-kappa B
Predicate
AUGMENTS
Object
Transcriptio
3. Discordance COEXISTS_WITH COVID-19
Subject
Discordance
Predicate
COEXISTS_WITH
Object
COVID-19
4. Hospitalization TREATS Patients
Subject
Hospitalization
Predicate
TREATS
Object
Patients
5. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
6. NF-kappa B AUGMENTS Transcription, Genetic
Subject
NF-kappa B
Predicate
AUGMENTS
Object
Transcription, Genetic
7. Discordance COEXISTS_WITH COVID-19
Subject
Discordance
Predicate
COEXISTS_WITH
Object
COVID-19
8. Hospitalization TREATS Patients
Subject
Hospitalization
Predicate
TREATS
Object
Patients
ABSTRACT
Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.
Subject(s)
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Observational study / Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.144455

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Observational study / Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.144455