Kinetic Analysis of Biomarkers in a Cohort of US Patients With Ebola Virus Disease

• Type of Material: Article
• Authors: Anita McElroy, Emory University; Jessica R. Harmon, US Centers for Disease Control and Prevention; Timothy D. Flietstra, US Centers for Disease Control and Prevention; Shelley Campbell, US Centers for Disease Control and Prevention; Aneesh Mehta, Emory University; Colleen Kraft, Emory University; Marshall G. Lyon, Emory University; Jay Varkey, Emory University; Bruce Ribner, Emory University; Christopher J. Kratochvil, University of Nebraska Medical Center; Peter C. Iwen, University of Nebraska Medical Center; Philip W. Smith, University of Nebraska Medical Center; Rafi Ahmed, Emory University; Stuart Nichol, Emory University; Christina Spiropoulou, Emory University
• Language: English
• Date: 2016-08-15
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Published by Oxford University Press for the Infectious Diseases Society of America 2016.
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciw334
• Title of Journal or Parent Work: Clinical Infectious Diseases
• ISSN: 1058-4838
• Volume: 63
• Issue: 4
• Start Page: 460
• End Page: 467
• Grant/Funding Information: This work was supported by the CDC, the National Institutes of Health Atlanta Pediatric Scholars program (K12HD072245 to A. K. M.), the Defense Advanced Research Projects Agency (W31P4Q-14-1-0010 to R. A.), and the Burroughs Wellcome Fund (1013362.01 to A. K. M.).
• Keywords: EVD; immunity; UNITED-STATES; ACTIVATION; INFECTED PATIENTS; MANAGEMENT; CONVALESCENT PLASMA; Science & Technology; Immunology; APOPTOSIS; Ebola; biomarkers; Infectious Diseases; Life Sciences & Biomedicine; cytokines; HEMORRHAGIC-FEVER; SIERRA-LEONE; OUTBREAK; RESPONSES; Microbiology
• Research Categories: Health Sciences, Pathology; Biology, Microbiology

Abstract

Background. 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. Methods. 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. Results. 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. Conclusions. 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.