TY - JOUR
T1 - Relationship between Viremia and Specific Organ Damage in Ebola Patients
T2 - A Cohort Study
AU - Lanini, Simone
AU - Portella, Gina
AU - Vairo, Francesco
AU - Kobinger, Gary P.
AU - Pesenti, Antonio
AU - Langer, Martin
AU - Kabia, Soccoh
AU - Brogiato, Giorgio
AU - Amone, Jackson
AU - Castilletti, Concetta
AU - Miccio, Rossella
AU - Capobianchi, Maria Rosaria
AU - Strada, Gino
AU - Zumla, Alimuddin
AU - Di Caro, Antonino
AU - Ippolito, Giuseppe
AU - Biava, Mirella
AU - Cannas, Angela
AU - Chiappini, Roberta
AU - Coen, Sabrina
AU - Colavita, Francesca
AU - Grassi, Germana
AU - Lapa, Daniele
AU - Mazzarelli, Antonio
AU - Meschi, Silvia
AU - Minosse, Claudia
AU - Quartu, Serena
AU - Valli, Maria Beatrice
AU - Venditti, Carolina
AU - Vulcano, Antonella
AU - Zaccaro, Paola
AU - Ahmad, Umar
AU - Checcarelli, Elisabetta
AU - Guanti, Michela Delli
AU - Giovanella, Elena
AU - Gottardello, Davide
AU - Guastalegname, Maurizio
AU - Jocic, Milos
AU - Monti, Giorgio
AU - Parsons, Clare
AU - Rossi, Nicola
AU - Salvati, Giampiero
AU - Scaccabarozzi, Giovanna
AU - Sisillo, Erminio
AU - Tagliabue, Paola
AU - Turella, Marta
AU - Valdatta, Caterina
N1 - Funding Information:
1National Institute for Infectious Diseases “Lazzaro Spallanzani,” Istituto di Ricovero e Cura a Carattere Scientifico , Rome, Italy; 2International Public Health Crisis Group; 3EMERGENCY, Milan, Italy; 4Research Centre on Infectious Diseases, Faculty of Medicine, Université Laval, Québec, Canada; 5Department 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, and 6Department of Oncology and Onco-Hematology, University of Milan, and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 7Connaught Hospital Tower Hill, Freetown, Sierra Leone; 8Department of Clinical Services, Ministry of Health, Kampala, Uganda; and 9Division 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
Funding Information:
Acknowledgments. Goderich ETC has been built by the Royal Engineers as proxy for the Department for International Development, UK Government (DFID), in cooperation with EMERGENCY’s Technical Division. The ETC’s operations have been cofunded by DFID and EMERGENCY’s private donations. The upgrading of the virology laboratory has been supported by a grant from the Italian Ministry of Foreign Affairs–Direzione General per la Cooperazione allo Sviluppo (DGCS). INMI’s research activities have been performed thanks to grants from the Italian Ministry of Health (Ricerca Corrente IRCCS and Ricerca Finalizzata). Deployment of laboratory personnel was possible thanks to a grant from the Italian Ministry of Foreign Affairs–DGCS. We thank the EMLab European consortium (IFS/2011/272–372; www.emlab.eu), which has been where we have developed the knowledge and experience that have allowed us to establish the virology laboratory at Goderich ETC. We thank the people who worked at the ETC in Goderich, Sierra Leone, and all members of the INMI-EMERGENCY EBOV Sierra Leone Study group.
Funding Information:
Financial support. This work was supported by the Italian Ministry of Health, Ricerca Corrente IRCCS; Italian Ministry of Foreign Affairs; EMERGENCY’s private donations; and Royal Engineers for the UK DFID.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Ebola virus
KW - biomarkers
KW - liver function
KW - muscle damage
KW - renal function.
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U2 - 10.1093/cid/cix704
DO - 10.1093/cid/cix704
M3 - Article
C2 - 29020340
AN - SCOPUS:85040633770
SN - 1058-4838
VL - 66
SP - 36
EP - 44
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -