Manuel Schibler1, Pauline Vetter2, Pascal Cherpillod3, Tom J Petty4, Samuel Cordey3, Gaël Vieille1, Sabine Yerly3, Claire-Anne Siegrist5, Kaveh Samii6, Julie-Anne Dayer7, Mylène Docquier8, Evgeny M Zdobnov4, Andrew J H Simpson9, Paul S C Rees10, Felix Baez Sarria11, Yvan Gasche12, François Chappuis13, Anne Iten14, Didier Pittet14, Jérôme Pugin12, Laurent Kaiser3. 1. 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. 2. 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. 3. 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. 4. Swiss Institute of Bioinformatics, Geneva, Switzerland; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. 5. Departments of Pathology and Immunology, and Paediatrics, WHO Collaborating Centre for Vaccine Immunology, Geneva University Hospitals and University of Geneva Medical School, Geneva, Switzerland. 6. Department of Haematology, Geneva University Hospitals, Geneva, Switzerland. 7. Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland. 8. University of Geneva Medical School, and Genomics Platform, Geneva, Switzerland. 9. Rare and Imported Pathogens Laboratory, Public Health England, Wiltshire, UK. 10. Academic Department of Military Medicine, Barts Health NHS Trust and Defence Medical Services, London, UK. 11. Hospital Universitario Dr Carlos J Finlay, Marianao, La Habana, Cuba. 12. Intensive Care Unit, Geneva University Hospitals, Geneva, Switzerland. 13. Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland. 14. Infection Control Programme, and WHO Collaborating Centre on Patient Safety, Geneva University Hospitals and University of Geneva Medical School, Geneva, Switzerland.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.
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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.
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