Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study

Romy Kerber; Eva Lorenz; Sophie Duraffour; Daouda Sissoko; Martin Rudolf; Anna Jaeger; Sekou Ditinn Cisse; Alseny-Modet Camara; Osvaldo Miranda; Carlos Castro; Joseph Akoi Bore; Fara Raymond Koundouno; Johanna Reptis; Babak Afrough; Beate Becker-Ziaja; Julia Hinzmann; Marc Mertens; Ines Vitoriano; Christopher Logue; Jan-Peter Bottcher; Elisa Pallasch; Andreas Sachse; Amadou Bah; Mar Cabeza-Cabrerizo; Katja Nitzsche; Eeva Kuisma; Janine Michel; Tobias Holm; Elsa Zekeng; Lauren Cowley; Isabel Garcia-Dorival; Nicole Hetzelt; Jonathan Baum; Jasmine Portmann; Lisa Carter; Rahel Yenamaberhan; Alvaro Camino; Theresa Enkirch; Katrin Singethan; Sarah Meisel; Antonio Mazzarelli; Abigail Kosgei; Liana Kafetzopoulou; Natasha Rickett; Livia Patrono; Luam Ghebreghiorghis; Ulrike Arnold; Geraldine Colin; Sylvain Juchet; Claire Levy Marchal; Jacques Seraphin Kolie; Abdoul Habib Beavogui; Stephanie Wurr; Sabrina Bockholt; Ralf Krumkamp; Jurgen May; Kilian Stoecker; Erna Fleischmann; Giuseppe Ippolito; Miles Carroll; Lamine Koivogui; N'Faly Magassouba; Sakoba Keita; Céline Gurry; Patrick Drury; Boubacar Diallo; Pierre Formenty; Roman Wölfel; Antonino Di Caro; Martin Gabriel; Xavier Anglaret; Denis Malvy; Stephan Günther

doi:10.1093/infdis/jiz078

Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study

Romy Kerber, Eva Lorenz, Sophie Duraffour, Daouda Sissoko, Martin Rudolf, Anna Jaeger, Sekou Ditinn Cisse, Alseny-Modet Camara, Osvaldo Miranda, Carlos Castro, Joseph Akoi Bore, Fara Raymond Koundouno, Johanna Reptis, Babak Afrough, Beate Becker-Ziaja, Julia Hinzmann, Marc Mertens, Ines Vitoriano, Christopher Logue, Jan-Peter BottcherElisa Pallasch, Andreas Sachse, Amadou Bah, Mar Cabeza-Cabrerizo, Katja Nitzsche, Eeva Kuisma, Janine Michel, Tobias Holm, Elsa Zekeng, Lauren Cowley, Isabel Garcia-Dorival, Nicole Hetzelt, Jonathan Baum, Jasmine Portmann, Lisa Carter, Rahel Yenamaberhan, Alvaro Camino, Theresa Enkirch, Katrin Singethan, Sarah Meisel, Antonio Mazzarelli, Abigail Kosgei, Liana Kafetzopoulou, Natasha Rickett, Livia Patrono, Luam Ghebreghiorghis, Ulrike Arnold, Geraldine Colin, Sylvain Juchet, Claire Levy Marchal, Jacques Seraphin Kolie, Abdoul Habib Beavogui, Stephanie Wurr, Sabrina Bockholt, Ralf Krumkamp, Jurgen May, Kilian Stoecker, Erna Fleischmann, Giuseppe Ippolito, Miles Carroll, Lamine Koivogui, N'Faly Magassouba, Sakoba Keita, Céline Gurry, Patrick Drury, Boubacar Diallo, Pierre Formenty, Roman Wölfel, Antonino Di Caro, Martin Gabriel, Xavier Anglaret, Denis Malvy, Stephan Günther

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Abstract

Background
In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.

Methods
To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.

Results
The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.

Conclusions
Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Original language	English
Pages (from-to)	195-202
Number of pages	8
Journal	Journal of Infectious Diseases
Volume	220
Issue number	2
Early online date	21 Feb 2019
DOIs	https://doi.org/10.1093/infdis/jiz078
Publication status	Published - 15 Jul 2019

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Kerber, R., Lorenz, E., Duraffour, S., Sissoko, D., Rudolf, M., Jaeger, A., Cisse, S. D., Camara, A.-M., Miranda, O., Castro, C., Bore, J. A., Koundouno, F. R., Reptis, J., Afrough, B., Becker-Ziaja, B., Hinzmann, J., Mertens, M., Vitoriano, I., Logue, C., ... Günther, S. (2019). Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study. Journal of Infectious Diseases, 220(2), 195-202. https://doi.org/10.1093/infdis/jiz078

Kerber, R, Lorenz, E, Duraffour, S, Sissoko, D, Rudolf, M, Jaeger, A, Cisse, SD, Camara, A-M, Miranda, O, Castro, C, Bore, JA, Koundouno, FR, Reptis, J, Afrough, B, Becker-Ziaja, B, Hinzmann, J, Mertens, M, Vitoriano, I, Logue, C, Bottcher, J-P, Pallasch, E, Sachse, A, Bah, A, Cabeza-Cabrerizo, M, Nitzsche, K, Kuisma, E, Michel, J, Holm, T, Zekeng, E, Cowley, L, Garcia-Dorival, I, Hetzelt, N, Baum, J, Portmann, J, Carter, L, Yenamaberhan, R, Camino, A, Enkirch, T, Singethan, K, Meisel, S, Mazzarelli, A, Kosgei, A, Kafetzopoulou, L, Rickett, N, Patrono, L, Ghebreghiorghis, L, Arnold, U, Colin, G, Juchet, S, Marchal, CL, Seraphin Kolie, J, Beavogui, AH, Wurr, S, Bockholt, S, Krumkamp, R, May, J, Stoecker, K, Fleischmann, E, Ippolito, G, Carroll, M, Koivogui, L, Magassouba, NF, Keita, S, Gurry, C, Drury, P, Diallo, B, Formenty, P, Wölfel, R, Di Caro, A, Gabriel, M, Anglaret, X, Malvy, D & Günther, S 2019, 'Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study', Journal of Infectious Diseases, vol. 220, no. 2, pp. 195-202. https://doi.org/10.1093/infdis/jiz078

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title = "Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study",

abstract = "BackgroundIn 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.MethodsTo reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.ResultsThe case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.ConclusionsConsistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.",

author = "Romy Kerber and Eva Lorenz and Sophie Duraffour and Daouda Sissoko and Martin Rudolf and Anna Jaeger and Cisse, {Sekou Ditinn} and Alseny-Modet Camara and Osvaldo Miranda and Carlos Castro and Bore, {Joseph Akoi} and Koundouno, {Fara Raymond} and Johanna Reptis and Babak Afrough and Beate Becker-Ziaja and Julia Hinzmann and Marc Mertens and Ines Vitoriano and Christopher Logue and Jan-Peter Bottcher and Elisa Pallasch and Andreas Sachse and Amadou Bah and Mar Cabeza-Cabrerizo and Katja Nitzsche and Eeva Kuisma and Janine Michel and Tobias Holm and Elsa Zekeng and Lauren Cowley and Isabel Garcia-Dorival and Nicole Hetzelt and Jonathan Baum and Jasmine Portmann and Lisa Carter and Rahel Yenamaberhan and Alvaro Camino and Theresa Enkirch and Katrin Singethan and Sarah Meisel and Antonio Mazzarelli and Abigail Kosgei and Liana Kafetzopoulou and Natasha Rickett and Livia Patrono and Luam Ghebreghiorghis and Ulrike Arnold and Geraldine Colin and Sylvain Juchet and Marchal, {Claire Levy} and {Seraphin Kolie}, Jacques and Beavogui, {Abdoul Habib} and Stephanie Wurr and Sabrina Bockholt and Ralf Krumkamp and Jurgen May and Kilian Stoecker and Erna Fleischmann and Giuseppe Ippolito and Miles Carroll and Lamine Koivogui and N'Faly Magassouba and Sakoba Keita and C{\'e}line Gurry and Patrick Drury and Boubacar Diallo and Pierre Formenty and Roman W{\"o}lfel and {Di Caro}, Antonino and Martin Gabriel and Xavier Anglaret and Denis Malvy and Stephan G{\"u}nther",

year = "2019",

month = jul,

day = "15",

doi = "10.1093/infdis/jiz078",

language = "English",

volume = "220",

pages = "195--202",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "2",

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TY - JOUR

T1 - Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study

AU - Kerber, Romy

AU - Lorenz, Eva

AU - Duraffour, Sophie

AU - Sissoko, Daouda

AU - Rudolf, Martin

AU - Jaeger, Anna

AU - Cisse, Sekou Ditinn

AU - Camara, Alseny-Modet

AU - Miranda, Osvaldo

AU - Castro, Carlos

AU - Bore, Joseph Akoi

AU - Koundouno, Fara Raymond

AU - Reptis, Johanna

AU - Afrough, Babak

AU - Becker-Ziaja, Beate

AU - Hinzmann, Julia

AU - Mertens, Marc

AU - Vitoriano, Ines

AU - Logue, Christopher

AU - Bottcher, Jan-Peter

AU - Pallasch, Elisa

AU - Sachse, Andreas

AU - Bah, Amadou

AU - Cabeza-Cabrerizo, Mar

AU - Nitzsche, Katja

AU - Kuisma, Eeva

AU - Michel, Janine

AU - Holm, Tobias

AU - Zekeng, Elsa

AU - Cowley, Lauren

AU - Garcia-Dorival, Isabel

AU - Hetzelt, Nicole

AU - Baum, Jonathan

AU - Portmann, Jasmine

AU - Carter, Lisa

AU - Yenamaberhan, Rahel

AU - Camino, Alvaro

AU - Enkirch, Theresa

AU - Singethan, Katrin

AU - Meisel, Sarah

AU - Mazzarelli, Antonio

AU - Kosgei, Abigail

AU - Kafetzopoulou, Liana

AU - Rickett, Natasha

AU - Patrono, Livia

AU - Ghebreghiorghis, Luam

AU - Arnold, Ulrike

AU - Colin, Geraldine

AU - Juchet, Sylvain

AU - Marchal, Claire Levy

AU - Seraphin Kolie, Jacques

AU - Beavogui, Abdoul Habib

AU - Wurr, Stephanie

AU - Bockholt, Sabrina

AU - Krumkamp, Ralf

AU - May, Jurgen

AU - Stoecker, Kilian

AU - Fleischmann, Erna

AU - Ippolito, Giuseppe

AU - Carroll, Miles

AU - Koivogui, Lamine

AU - Magassouba, N'Faly

AU - Keita, Sakoba

AU - Gurry, Céline

AU - Drury, Patrick

AU - Diallo, Boubacar

AU - Formenty, Pierre

AU - Wölfel, Roman

AU - Di Caro, Antonino

AU - Gabriel, Martin

AU - Anglaret, Xavier

AU - Malvy, Denis

AU - Günther, Stephan

PY - 2019/7/15

Y1 - 2019/7/15

N2 - BackgroundIn 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.MethodsTo reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.ResultsThe case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.ConclusionsConsistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

AB - BackgroundIn 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus–specific reverse transcription–polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.MethodsTo reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.ResultsThe case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.ConclusionsConsistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

U2 - 10.1093/infdis/jiz078

DO - 10.1093/infdis/jiz078

M3 - Article

SN - 0022-1899

VL - 220

SP - 195

EP - 202

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 2

ER -

Laboratory findings, compassionate use of Favipiravir, and outcome in patients with Ebola virus disease, guinea, 2015—a retrospective observational study

Abstract

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