title: Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report.
abstract: BACKGROUND
  A detailed description of viral kinetics, duration of virus shedding, and intraviral evolution in different body sites is warranted to understand Ebola virus pathogenesis. Patients with Ebola virus infections admitted to university hospitals provide a unique opportunity to do such in-depth virological investigations. We describe the clinical, biological, and virological follow-up of a case of Ebola virus disease.
  
  
  METHODS
  A 43-year-old medical doctor who contracted an Ebola virus infection in Sierra Leone on Nov 16, 2014 (day 1), was airlifted to Geneva University Hospitals, Geneva, Switzerland, on day 5 after disease onset. The patient received an experimental antiviral treatment of monoclonal antibodies (ZMAb) and favipiravir. We monitored daily viral load kinetics, estimated viral clearance, calculated the half-life of the virus in plasma, and analysed the viral genome via high-throughput sequencing, in addition to clinical and biological signs.
  
  
  RESULTS
  The patient recovered rapidly, despite an initial high viral load (about 1 × 10(7) RNA copies per mL 24 h after onset of fever). We noted a two-phase viral decay. The virus half-life decreased from about 26 h to 9·5 h after the experimental antiviral treatment. Compared with a consensus sequence of June 18, 2014, the isolate that infected this patient displayed only five synonymous nucleotide substitutions on the full genome (4901A→C, 7837C→T, 8712A→G, 9947T→C, 16201T→C) despite 5 months of human-to-human transmission.
  
  
  CONCLUSIONS
  This study emphasises the importance of virological investigations to fully understand the course of Ebola virus disease and adaptation of the virus. Whether the viral decay was caused by the effects of the immune response alone, an additional benefit from the antiviral treatment, or a combination of both is unclear. In-depth virological analysis and randomised controlled trials are needed before any conclusion on the potential effect of antiviral treatment can be drawn.
  
  
  BACKGROUND
  Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schibler
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland. Electronic address: pauline.vetter@hcuge.ch.
authors.forename: Pauline
authors.initials: P
authors.lastname: Vetter
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cherpillod
authors.affiliation: Swiss Institute of Bioinformatics, Geneva, Switzerland; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Petty
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Cordey
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Gaël
authors.initials: G
authors.lastname: Vieille
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.affiliation: Departments of Pathology and Immunology, and Paediatrics, WHO Collaborating Centre for Vaccine Immunology, Geneva University Hospitals and University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.affiliation: Department of Haematology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Samii
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Julie-Anne
authors.initials: JA
authors.lastname: Dayer
authors.affiliation: University of Geneva Medical School, and Genomics Platform, Geneva, Switzerland.
authors.forename: Mylène
authors.initials: M
authors.lastname: Docquier
authors.affiliation: Swiss Institute of Bioinformatics, Geneva, Switzerland; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Evgeny M
authors.initials: EM
authors.lastname: Zdobnov
authors.affiliation: Rare and Imported Pathogens Laboratory, Public Health England, Wiltshire, UK.
authors.forename: Andrew J H
authors.initials: AJH
authors.lastname: Simpson
authors.affiliation: Academic Department of Military Medicine, Barts Health NHS Trust and Defence Medical Services, London, UK.
authors.forename: Paul S C
authors.initials: PSC
authors.lastname: Rees
authors.affiliation: Hospital Universitario Dr Carlos J Finlay, Marianao, La Habana, Cuba.
authors.forename: Felix Baez
authors.initials: FB
authors.lastname: Sarria
authors.affiliation: Intensive Care Unit, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.affiliation: Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Chappuis
authors.affiliation: Infection Control Programme, and WHO Collaborating Centre on Patient Safety, Geneva University Hospitals and University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Iten
authors.affiliation: Infection Control Programme, and WHO Collaborating Centre on Patient Safety, Geneva University Hospitals and University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Pittet
authors.affiliation: Intensive Care Unit, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pugin
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Virology and Swiss Reference Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
mesh_terms: D000328:Adult; D000577:Amides / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D029043:Ebolavirus / Q000235:genetics*; D016679:Genome, Viral; D006207:Half-Life; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D011719:Pyrazines / Q000627:therapeutic use; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; C462182:favipiravir