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Research Article
Long-lasting severe immune dysfunction in Ebola virus disease survivors
Yves Lévy, M.D.
Vaccine Research Institute, Université Paris-Est Créteil, Faculté de Médecine, INSERM U955, Team 16, Créteil, France
Corresponding Author
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Clinical follow-up of Ebola virus disease (EVD) survivors revealed a persistence of clinical symptoms and higher risk of mortality. Long-term analyses of the immune and inflammatory profiles of EVD survivors are currently lacking. Here, we evaluate immune profile status and gene expression profiles in 35 Guinean EVD survivors (EBOV_S) from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from the Ebola treatment center. We show a persistent increase of several biomarkers of inflammation, immune activation and gut tissue damage in EBOV_S compared to healthy donors living in the same area. These results are confirmed by phenotypic characterization of immune cell subsets revealing increases in activation marker expression and the frequencies of CD8+ T cells, exhausted B cells, non-classical NK cells and circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing studies of the genes expressed in blood revealed a significant enrichment in genes associated with antiviral responses in EBOV_S.
This study assess the long-term persistence of immunological dysfunction in survivors and identify a set of biological and genetic markers that could be used to define a signature of “chronic Ebola virus disease (CEVD)”.
Keywords
immunological dysfunction, Ebola, biomarkers of inflammation, immune activation, gut tissue damage
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Fara michel Ifono
commented on 13 July, 2020
Je suis titulaire du diplôme en es sciences biologiques à l'Université Julius N'yéréré de kankan désireux de poursuivre ma formation en techniques de laboratoire. Merci et bonne réception.
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This preprint is under consideration at a Nature Research Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Nature journals have partnered with Research Square to offer In Review, a journal-integrated preprint deposition service.
Research Article
Long-lasting severe immune dysfunction in Ebola virus disease survivors
Yves Lévy, M.D.
Vaccine Research Institute, Université Paris-Est Créteil, Faculté de Médecine, INSERM U955, Team 16, Créteil, France
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 27 Sep, 2019
Metrics
Comments: 1
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Clinical follow-up of Ebola virus disease (EVD) survivors revealed a persistence of clinical symptoms and higher risk of mortality. Long-term analyses of the immune and inflammatory profiles of EVD survivors are currently lacking. Here, we evaluate immune profile status and gene expression profiles in 35 Guinean EVD survivors (EBOV_S) from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from the Ebola treatment center. We show a persistent increase of several biomarkers of inflammation, immune activation and gut tissue damage in EBOV_S compared to healthy donors living in the same area. These results are confirmed by phenotypic characterization of immune cell subsets revealing increases in activation marker expression and the frequencies of CD8+ T cells, exhausted B cells, non-classical NK cells and circulating dendritic cells. All survivors have EBOV-specific IgG antibodies and robust and polyfunctional EBOV-specific memory T-cell responses. Deep sequencing studies of the genes expressed in blood revealed a significant enrichment in genes associated with antiviral responses in EBOV_S.
This study assess the long-term persistence of immunological dysfunction in survivors and identify a set of biological and genetic markers that could be used to define a signature of “chronic Ebola virus disease (CEVD)”.
Figure 1
Figure 2
Figure 3
Figure 4
Fara michel Ifono
commented on 13 July, 2020
Je suis titulaire du diplôme en es sciences biologiques à l'Université Julius N'yéréré de kankan désireux de poursuivre ma formation en techniques de laboratoire. Merci et bonne réception.