Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era

Abstract This study aimed to characterize ophthalmological manifestations and associated inflammatory markers in EVD survivors in post-treatment era. Case-control study of ophthalmological manifestations and plasma inflammatory biomarker profile in EVD survivors (n = 120) from the 2018–2020 outbreak...

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Main Authors: Jean-Claude Mwanza, Alexis K. Kahindo, Justin Mbusa-Kombi, Martial V. Mumbere, Richard O. Kitenge, David R. McIlwain, Jean Christophe S. Mulangu, Placide K. Mbala, Daniel Okitundu, Bruno J. Giordani, Michael J. Boivin, Alla Sikorskii, Nelly N. Kabedi, Jessica G. Shantha, Steven Yeh, Dieudonne N. Mumba, Desire Tshala-Katumbay
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-96256-4
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author Jean-Claude Mwanza
Alexis K. Kahindo
Justin Mbusa-Kombi
Martial V. Mumbere
Richard O. Kitenge
David R. McIlwain
Jean Christophe S. Mulangu
Placide K. Mbala
Daniel Okitundu
Bruno J. Giordani
Michael J. Boivin
Alla Sikorskii
Nelly N. Kabedi
Jessica G. Shantha
Steven Yeh
Dieudonne N. Mumba
Desire Tshala-Katumbay
author_facet Jean-Claude Mwanza
Alexis K. Kahindo
Justin Mbusa-Kombi
Martial V. Mumbere
Richard O. Kitenge
David R. McIlwain
Jean Christophe S. Mulangu
Placide K. Mbala
Daniel Okitundu
Bruno J. Giordani
Michael J. Boivin
Alla Sikorskii
Nelly N. Kabedi
Jessica G. Shantha
Steven Yeh
Dieudonne N. Mumba
Desire Tshala-Katumbay
author_sort Jean-Claude Mwanza
collection DOAJ
description Abstract This study aimed to characterize ophthalmological manifestations and associated inflammatory markers in EVD survivors in post-treatment era. Case-control study of ophthalmological manifestations and plasma inflammatory biomarker profile in EVD survivors (n = 120) from the 2018–2020 outbreak in DRC, their gender- and age-matched close contacts (n = 120) and non-contact (healthy) controls (n = 120). Expressions of inflammatory markers were assessed using the Olink Explore 384 Assay and compared across study groups before and after stratification by treatment with monoclonal antibodies (mAB114, ZMapp, or Regeneron) or antiviral drug (Remdesivir). Protein profiling was carried out using the Olink statistical package. Mean age (years) was comparable among survivors (29.7 ± 10.6), close contacts (28.9 ± 11.1) and non-contact controls (29.3 ± 10.6) (p = 0.85). Mean time from disease onset to clinical assessment was 3.5 ± 0.5 (2.5–4.2) years in survivors. Optic neuropathy was more common in survivors (6.7%) than in close contacts (0.8%) and non-contacts (0.0%) (p = 0.003). Survivors with optic neuropathy had significantly worse visual acuity in both eyes than those without optic neuropathy (all p < 0.001). Clinical evidence of past anterior uveitis was observed in 2.5% of survivors, 2.9% of close contacts, and 1.8% of healthy controls (p = 0.86). Plasma circulating DGKZ, INFGR1, ERBB3, and MICA-MICB showed differential expression patterns between survivors and controls (all p < 0.05). However, no clear separation could be detected on principal component analysis of multiplexed proteomic data between survivor and control samples. Three proteins (ITM2A, CLEC4D, NCLN) were differentially expressed and related to optic neuropathy. The comparison between treatment groups revealed a trend toward lower protein inflammatory markers in survivors treated with Remdesivir than those treated with monoclonal antibodies. We conclude that in treated EVD survivors, optic neuropathy was the only neuro-ophthalmologic abnormality. Uveitis was far less frequent than reported in West African cohorts. ITM2A, CLEC4D, and NCLN were differentially expressed in EVD survivors with optic neuropathy long after the acute phase of the infection. The true meaning of these findings will need further investigations.
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spelling doaj-art-9efc7ebb82ac4a36be7a8a304af0e5842025-08-20T03:52:19ZengNature PortfolioScientific Reports2045-23222025-04-0115111210.1038/s41598-025-96256-4Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment eraJean-Claude Mwanza0Alexis K. Kahindo1Justin Mbusa-Kombi2Martial V. Mumbere3Richard O. Kitenge4David R. McIlwain5Jean Christophe S. Mulangu6Placide K. Mbala7Daniel Okitundu8Bruno J. Giordani9Michael J. Boivin10Alla Sikorskii11Nelly N. Kabedi12Jessica G. Shantha13Steven Yeh14Dieudonne N. Mumba15Desire Tshala-Katumbay16Department of Ophthalmology, University of North Carolina at Chapel HillDepartment of Ophthalmology, Catholic University of GrabenDepartment of Neurology, University of KinshasaDepartment of Neurology & Psychiatry, Catholic University of GrabenNational Emergency Program, Ministry of HealthDepartment of Microbiology and Immunology, University of NevadaNational Institute for Biomedical ResearchNational Institute for Biomedical ResearchDepartment of Neurology, University of KinshasaMichigan Alzheimer’s Disease Research Center, University of MichiganDepartment of Psychiatry, Michigan State UniversityDepartment of Psychiatry, College of Osteopathic Medicine, Michigan State UniversityDepartment of Ophthalmology, University of KinshasaDepartment of Ophthalmology, F.I. Proctor Foundation, University of California San FranciscoTruhlsen Eye Institute, University of Nebraska Medical CenterNational Institute for Biomedical ResearchDepartment of Neurology, University of KinshasaAbstract This study aimed to characterize ophthalmological manifestations and associated inflammatory markers in EVD survivors in post-treatment era. Case-control study of ophthalmological manifestations and plasma inflammatory biomarker profile in EVD survivors (n = 120) from the 2018–2020 outbreak in DRC, their gender- and age-matched close contacts (n = 120) and non-contact (healthy) controls (n = 120). Expressions of inflammatory markers were assessed using the Olink Explore 384 Assay and compared across study groups before and after stratification by treatment with monoclonal antibodies (mAB114, ZMapp, or Regeneron) or antiviral drug (Remdesivir). Protein profiling was carried out using the Olink statistical package. Mean age (years) was comparable among survivors (29.7 ± 10.6), close contacts (28.9 ± 11.1) and non-contact controls (29.3 ± 10.6) (p = 0.85). Mean time from disease onset to clinical assessment was 3.5 ± 0.5 (2.5–4.2) years in survivors. Optic neuropathy was more common in survivors (6.7%) than in close contacts (0.8%) and non-contacts (0.0%) (p = 0.003). Survivors with optic neuropathy had significantly worse visual acuity in both eyes than those without optic neuropathy (all p < 0.001). Clinical evidence of past anterior uveitis was observed in 2.5% of survivors, 2.9% of close contacts, and 1.8% of healthy controls (p = 0.86). Plasma circulating DGKZ, INFGR1, ERBB3, and MICA-MICB showed differential expression patterns between survivors and controls (all p < 0.05). However, no clear separation could be detected on principal component analysis of multiplexed proteomic data between survivor and control samples. Three proteins (ITM2A, CLEC4D, NCLN) were differentially expressed and related to optic neuropathy. The comparison between treatment groups revealed a trend toward lower protein inflammatory markers in survivors treated with Remdesivir than those treated with monoclonal antibodies. We conclude that in treated EVD survivors, optic neuropathy was the only neuro-ophthalmologic abnormality. Uveitis was far less frequent than reported in West African cohorts. ITM2A, CLEC4D, and NCLN were differentially expressed in EVD survivors with optic neuropathy long after the acute phase of the infection. The true meaning of these findings will need further investigations.https://doi.org/10.1038/s41598-025-96256-4Ebola virus diseaseEbola treatmentOptic neuropathyInflammatory markersUveitis
spellingShingle Jean-Claude Mwanza
Alexis K. Kahindo
Justin Mbusa-Kombi
Martial V. Mumbere
Richard O. Kitenge
David R. McIlwain
Jean Christophe S. Mulangu
Placide K. Mbala
Daniel Okitundu
Bruno J. Giordani
Michael J. Boivin
Alla Sikorskii
Nelly N. Kabedi
Jessica G. Shantha
Steven Yeh
Dieudonne N. Mumba
Desire Tshala-Katumbay
Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
Scientific Reports
Ebola virus disease
Ebola treatment
Optic neuropathy
Inflammatory markers
Uveitis
title Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
title_full Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
title_fullStr Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
title_full_unstemmed Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
title_short Ophthalmological manifestations and plasma markers of inflammation in Ebola survivors in post-treatment era
title_sort ophthalmological manifestations and plasma markers of inflammation in ebola survivors in post treatment era
topic Ebola virus disease
Ebola treatment
Optic neuropathy
Inflammatory markers
Uveitis
url https://doi.org/10.1038/s41598-025-96256-4
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