title: Kinetic Analysis of Biomarkers in a Cohort of US Patients With Ebola Virus Disease.
abstract: Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease.
  
  
  
  In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention.
  
  
  
  Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease.
  
  
  
  Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD.
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention Division of Pediatric Infectious Disease.
authors.forename: Anita K
authors.initials: AK
authors.lastname: McElroy
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention Division of Pediatric Infectious Disease.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Harmon
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Flietstra
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention.
authors.forename: Shelley
authors.initials: S
authors.lastname: Campbell
authors.affiliation: Emory Vaccine Center Division of Infectious Diseases.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Division of Infectious Diseases Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.affiliation: Division of Infectious Diseases.
authors.forename: Marshall G
authors.initials: MG
authors.lastname: Lyon
authors.affiliation: Division of Infectious Diseases.
authors.forename: Jay B
authors.initials: JB
authors.lastname: Varkey
authors.affiliation: Division of Infectious Diseases.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Ribner
authors.affiliation: Office of the Vice Chancellor for Research, University of Nebraska Medical Center.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kratochvil
authors.affiliation: Department of Pathology and Microbiology.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Iwen
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center College of Medicine, Omaha.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Smith
authors.affiliation: Emory Vaccine Center.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Viral Special Pathogens Branch, US Centers for Disease Control and Prevention.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D018925:Chemokines / Q000097:blood*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D029043:Ebolavirus / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D056724:Immunity, Humoral; D007249:Inflammation; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014766:Viremia
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines
keywords: EVD; Ebola; biomarkers; cytokines; immunity