Simone Lanini1,2, Gina Portella3, Francesco Vairo1,2, Gary P Kobinger2,4, Antonio Pesenti3,5, Martin Langer3,6, Soccoh Kabia7, Giorgio Brogiato3, Jackson Amone8, Concetta Castilletti9, Rossella Miccio3, Maria Rosaria Capobianchi9, Gino Strada2,3, Alimuddin Zumla2,10, Antonino Di Caro1,2, Giuseppe Ippolito1,2. 1. National Institute for Infectious Diseases "Lazzaro Spallanzani," Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. 2. International Public Health Crisis Group, Milan, Italy. 3. EMERGENCY, Milan, Italy. 4. Research Centre on Infectious Diseases, Faculty of Medicine, Université Laval, Québec, Canada. 5. Department of Anesthesia, Critical Care Medicine and Emergency, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda-Ospedale Maggiore Policlinico, and Department of Pathophysiology and Transplantation, University of Milan. 6. Department of Oncology and Onco-Hematology, University of Milan, and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. Connaught Hospital Tower Hill, Freetown, Sierra Leone. 8. Department of Clinical Services, Ministry of Health, Kampala, Uganda. 9. National Institute for Infectious Diseases "Lazzaro Spallanzani," Istituto di Ricovero e Cura a Carattere Scientifico , Rome, Italy. 10. Division of Infection and Immunity, University College London, and National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust, United Kingdom.
Abstract
Background: Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods: We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood urea nitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results: One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions: This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.
Background: Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage. Methods: We recruited patients with detectable Ebola viremia admitted to the EMERGENCY Organizzazione Non Governativa Organizzazione Non Lucrativa di Utilità Sociale (ONG ONLUS) Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH), activated prothrombin time (aPTT), international normalized ratio (INR), creatinine, and blood ureanitrogen (BUN) were recorded. Patients were followed up from admission until death or discharge. Results: One hundred patients (49 survivors and 51 nonsurvivors) were included in the analysis. Unadjusted analysis to compare survivors and nonsurvivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in nonsurvivors than in survivors. Multivariable mixed-effects models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT, and INR. In contrast, no direct linear association was found between viremia and either creatinine, BUN, or bilirubin. Conclusions: This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not find strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.
Authors: Martin Langer; Gina Portella; Stefano Finazzi; Liliane Chatenoud; Simone Lanini; Francesco Vairo; Robert Fowler; Rossella Miccio; Giuseppe Ippolito; Guido Bertolini; Gino Strada Journal: Intensive Care Med Date: 2018-07-30 Impact factor: 17.440
Authors: Isaac Downs; Joshua C Johnson; Franco Rossi; David Dyer; David L Saunders; Nancy A Twenhafel; Heather L Esham; William D Pratt; John Trefry; Elizabeth Zumbrun; Paul R Facemire; Sara C Johnston; Erin L Tompkins; Nathan K Jansen; Anna Honko; Anthony P Cardile Journal: Viruses Date: 2021-11-17 Impact factor: 5.048
Authors: Whitney A Scoon; Liliana Mancio-Silva; Ellen L Suder; Carlos Villacorta-Martin; Jonathan Lindstrom-Vautrin; John G Bernbaum; Steve Mazur; Reed F Johnson; Judith Olejnik; Elizabeth Y Flores; Aditya Mithal; Feiya Wang; Adam J Hume; Joseph E Kaserman; Sandra March-Riera; Andrew A Wilson; Sangeeta N Bhatia; Elke Mühlberger; Gustavo Mostoslavsky Journal: Stem Cell Reports Date: 2022-09-08 Impact factor: 7.294
Authors: Jessica L Abbate; Pierre Becquart; Eric Leroy; Vanessa O Ezenwa; Benjamin Roche Journal: Emerg Infect Dis Date: 2020-02-17 Impact factor: 6.883
Authors: Christopher P Stefan; Catherine E Arnold; Charles J Shoemaker; Elizabeth E Zumbrun; Louis A Altamura; Christina E Douglas; Cheryl L Taylor-Howell; Amanda S Graham; Korey L Delp; Candace D Blancett; Keersten M Ricks; Scott P Olschner; Joshua D Shamblin; Suzanne E Wollen; Justine M Zelko; Holly A Bloomfield; Thomas R Sprague; Heather L Esham; Timothy D Minogue Journal: Microorganisms Date: 2021-03-23