Long-lasting severe immune dysfunction in Ebola virus disease survivors.
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ABSTRACT:
SUBMITTER: Wiedemann A
PROVIDER: S-EPMC7381622 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Long-lasting severe immune dysfunction in Ebola virus disease survivors.
Wiedemann Aurélie A Foucat Emile E Hocini Hakim H Lefebvre Cécile C Hejblum Boris P BP Durand Mélany M Krüger Miriam M Keita Alpha Kabinet AK Ayouba Ahidjo A Mély Stéphane S Fernandez José-Carlos JC Touré Abdoulaye A Fourati Slim S Lévy-Marchal Claire C Raoul Hervé H Delaporte Eric E Koivogui Lamine L Thiébaut Rodolphe R Lacabaratz Christine C Lévy Yves Y
Nature communications 20200724 1
Long-term follow up studies from Ebola virus disease (EVD) survivors (EBOV_S) are lacking. Here, we evaluate immune and gene expression profiles in 35 Guinean EBOV_S from the last West African outbreak, a median of 23 months (IQR [18-25]) after discharge from treatment center. Compared with healthy donors, EBOV_S exhibit increases of blood markers of inflammation, intestinal tissue damage, T cell and B cell activation and a depletion of circulating dendritic cells. All survivors have EBOV-specif ...[more]
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Project description:BackgroundEbola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD). We report the presence of Ebola virus RNA in semen in a cohort of survivors of EVD in Sierra Leone.MethodsWe enrolled a convenience sample of 220 adult male survivors of EVD in Sierra Leone, at various times after discharge from an Ebola treatment unit (ETU), in two phases (100 participants were in phase 1, and 120 in phase 2). Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target sequences of NP and VP40 (in phase 1) or NP and GP (in phase 2). This study did not evaluate directly the risk of sexual transmission of EVD.ResultsOf 210 participants who provided an initial semen specimen for analysis, 57 (27%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 7 men with a specimen obtained within 3 months after ETU discharge, in 26 of 42 (62%) with a specimen obtained at 4 to 6 months, in 15 of 60 (25%) with a specimen obtained at 7 to 9 months, in 4 of 26 (15%) with a specimen obtained at 10 to 12 months, in 4 of 38 (11%) with a specimen obtained at 13 to 15 months, in 1 of 25 (4%) with a specimen obtained at 16 to 18 months, and in no men with a specimen obtained at 19 months or later. Among the 46 participants with a positive result in phase 1, the median baseline cycle-threshold values (higher values indicate lower RNA values) for the NP and VP40 targets were lower within 3 months after ETU discharge (32.4 and 31.3, respectively; in 7 men) than at 4 to 6 months (34.3 and 33.1; in 25), at 7 to 9 months (37.4 and 36.6; in 13), and at 10 to 12 months (37.7 and 36.9; in 1). In phase 2, a total of 11 participants had positive results for NP and GP targets (samples obtained at 4.1 to 15.7 months after ETU discharge); cycle-threshold values ranged from 32.7 to 38.0 for NP and from 31.1 to 37.7 for GP.ConclusionsThese data showed the long-term presence of Ebola virus RNA in semen and declining persistence with increasing time after ETU discharge. (Funded by the World Health Organization and others.).
| S-EPMC5798881 | biostudies-literature
Project description:Monoclonal antibodies can mediate protection against Ebola virus (EBOV) infection through direct neutralization as well as through the recruitment of innate immune effector functions. However, the antibody functional response following survival of acute EBOV disease has not been well characterized. In this study, serum antibodies from Ebola virus disease (EVD) survivors from Sierra Leone were profiled to capture variation in overall subclass/isotype abundance, neutralizing activity, and innate immune effector functions. Antibodies from EVD survivors exhibited robust innate immune effector functions, mediated primarily by IgG1 and IgA1. In conclusion, development of functional antibodies follows survival of acute EVD.
| S-EPMC7184900 | biostudies-literature
Project description:IntroductionAn increased number of survivors have emerged from the 2014 West African Ebola Virus Disease (EVD) epidemic. Post-Ebola Syndrome (PES) is a group of physical and psychological symptoms affecting EVD survivors. This study aimed to estimate the prevalence of PES among EVD survivors in Montserrado County, Liberia.MethodA cross-sectional study design was conducted to determine the prevalence of PES, types, onset, and duration among survivors. Survivors in Montserrado County were recruited using multistage sampling methods. Quantitative data was collected using semistructured questionnaire. Variables were collected on EVD survivors demographics, pre- and post-Ebola health history.ResultPrevalence of Post-Ebola Syndrome was estimated to be 90% (242/268). PES was experienced by 67% (162/242) females. PES occurred mainly in the adult population between ages 25-34, 35% (84/242). The commonest symptoms were reported from the following systems of the human body: neurological system (eyes problem, headache, sleep disorder, and unusual tiredness) and musculoskeletal system (abdominal pain, chest pain, and joints pains). The onset of PES occurred between the first 1-12 weeks after being discharged from a treatment unit.ConclusionPrevalence of PES is high. Clinical care for survivors should be strengthened.
| S-EPMC6046154 | biostudies-literature
Project description:Immune patterns in Ebola patients were characterized depending on the outcome of the illness. Non-healthy controls were compared to Ebola patients to define the specificity of the immune response against Ebola virus infection.
2019-05-09 | GSE122692 | GEO
Project description:BackgroundThousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone.MethodsA survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors.ResultsA total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness.ConclusionsPost-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness.
| S-EPMC4872294 | biostudies-literature
Project description:BackgroundThe West African Ebola virus epidemic from 2014-2016 highlighted the lack of knowledge about the pathogenicity of the virus and the factors responsible for outcome. A performant and rapid diagnosis is of crucial importance, as is overcoming the difficulty of providing high-quality patient management during such an extensive outbreak. Here, we propose to study the role of the immune mediators during Ebola virus disease and to define some molecules of importance in the outcome.MethodsPlasma from Guinean patients sampled during the outbreak were analyzed using RT-qPCR, magnetic bead assay, ELISA, and high-quality statistical analyses. We also performed a transcriptomic analysis in leukocytes samples. Therefore, we deeply characterized the immune responses involved in Ebola virus disease.ResultsWe evaluated the immune patterns depending on the outcome of the disease. Survivors presented an efficient and well-balanced immune response, whereas fatalities were characterized by an intense inflammatory response, overexpression of multiple cytokines, and a "chemokine storm." The plasma concentration of most of the parameters tested increased until death. Statistical analyses also allowed us to define a panel of markers highly predictive of outcome.ConclusionThe immune response observed in fatalities was highly similar to that characterizing septic shock syndrome. Our results suggest that immune responses can play a major pathogenic role during severe Ebola virus infection and argue in favor of therapeutic approaches that act on both viral replication and the induction of shock syndrome.FundingFrench Ministry of Foreign Affairs, the Agence Française de Développement, and the Institut Pasteur.
| S-EPMC6485372 | biostudies-literature
Project description:BackgroundPersistence of Ebola virus (EBOV) in semen remains of deep concern, as sexual transmission of EBOV seems plausible up to 6 months after acute phase of Ebola virus disease (EVD). Favipiravir, a broad spectrum antiviral product, has been evaluated in reducing EVD mortality in Guinea in 2014-2015 in the JIKI trial, the pharmacokinetic results of which suggest that an increase of dose might be necessary to achieve a therapeutically relevant exposure. In FORCE trial, we aimed at evaluating the tolerance and activity of high doses of favipiravir in male EVD survivors with EBOV RNA detection in semen in Guinea.CaseIn 2016, we launched a phase IIa open-labeled multicenter dose escalation study. Male survivors of EVD with EBOV RT-PCR positive on semen received a loading dose of 2400 mg BID of favipiravir on day 1 then a maintenance dose of 1800 mg BID from day 2-14. The primary outcome was the tolerance, assessed daily during period treatment and up to day 90. Unfortunately only two participants were included and the trial was stopped for lack of recruitment. No clinical adverse event of grade 3/4 was reported for both patients. One patient experienced a grade 3 hypocalcemia at day 10 and 14.ConclusionsHigh doses of favipiravir were well tolerated in these two participants. Better characterized tolerance and pharmacokinetics of high doses of favipiravir are of utmost importance considering that favipiravir is a candidate treatment for a variety of emerging severe viral diseases with poor prognosis.
| S-EPMC8808076 | biostudies-literature
Project description:ImportanceDifferentiation between Ebola retinal lesions and other retinal pathologies in West Africa is important, and the pathogenesis of Ebola retinal disease remains poorly understood.ObjectiveTo describe the appearance of Ebola virus disease (EVD) retinal lesions using multimodal imaging to enable inferences on potential pathogenesis.Design, setting, and participantsThis prospective case series study was carried out at 34 Military Hospital in Freetown, Sierra Leone. Ophthalmological images were analyzed from 14 consecutively identified survivors of EVD of Sierra Leonean origin who had identified Ebola retinal lesions.Main outcomes and measuresMultimodal imaging findings including ultra-widefield scanning laser ophthalmoscopy, fundus autofluorescence, swept-source optical coherence tomography (OCT), Humphrey visual field analysis, and spatial analysis.ResultsThe 14 study participants had a mean (SD) age of 37.1 (8.8) years; 6 (43%) were women. A total of 141 Ebola retinal lesions were observed in 22 of 27 eyes (81%) of these 14 survivors on ultra-widefield imaging. Of these, 41 lesions (29.1%) were accessible to OCT imaging. Retinal lesions were predominantly nonpigmented with a pale-gray appearance. Peripapillary lesions exhibited variable curvatures in keeping with the retinal nerve fiber layer projections. All lesions respected the horizontal raphe and spared the fovea. The OCT imaging demonstrated a V-shaped hyperreflectivity of the outer nuclear layer overlying discontinuities of the ellipsoid zone and interdigitation zone in the smaller lesions. Larger lesions caused a collapse of the retinal layers and loss of retinal thickness. Lesion shapes were variable, but sharp angulations were characteristic. Perilesional areas of dark without pressure (thinned ellipsoid zone hyporeflectivity) accompanied 125 of the 141 lesions (88.7%) to varying extents.Conclusions and relevanceWe demonstrate OCT evidence of localized pathological changes at the level of the photoreceptors in small lesions among survivors of EVD with retinal lesions. The relevance of associated areas of dark without pressure remains undetermined.
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Project description:Background/objectivesEbola virus disease (EVD) survivors develop post-acute ophthalmic sequelae, including a high prevalence of uveitis that may be complicated by vision-threatening cataract. After the non-detection of Ebola virus (EBOV) RNA in sampled ocular fluid, vision impairment due to cataract can be treated safely and effectively via manual small incision cataract surgery (MSICS). However, the long-term ocular visual outcomes and assessment of ocular tissues, including for genomic RNA, have been infrequently or not reported in Western African survivors.Subjects/methodsA cohort of EVD survivors with visually significant cataract, in whom EBOV RNA was not detected by RT-PCR testing of ocular fluid sampled prior to MSICS, were followed for a year after intraocular lens replacement. Ophthalmic outcomes, including visual acuity (VA), adverse events, and follow-up examinations, were recorded. Ocular tissue specimens obtained at MSICS underwent histopathologic examination and in-situ hybridization (ISH) targeting EBOV genomic RNA.ResultsThirty-four EVD survivors underwent MSICS and were included for analysis. The median age of EVD survivors who underwent surgery at enrollment was 22.5 years (Interquartile range, IQR: 16.5-33) and the cohort was comprised of 20 females (58.8%). Median logMAR VA at preoperative baseline was 3 (IQR: 1-3) which improved to 0.4 (IQR: 0-0.6; n = 10; p = 0.002) and 0.6 (IQR: 0.18-0.78; n = 18; p < 0.0001) at 6- and 12-months following surgery, respectively. EBOV RNA was not detected in 7 cataract and capsular tissue specimens obtained at the time of MSICS.ConclusionsAfter MSICS, meaningful improvement in vision was maintained in EVD survivors at long-term follow-up. EBOV RNA was not detected in cataract and lens capsule specimens, providing additional reassurance of the low risk of EBOV RNA exposure during cataract surgery. Further study is needed to understand long-term ocular outcomes, including adverse events, in this population.Author summaryEbola virus disease (EVD) survivors may develop several ophthalmic sequelae including uveitis and cataract that may lead to severe vision loss if left untreated. Manual small incision cataract surgery (MSICS) has been utilized to treat cataract in EVD survivors with encouraging short-term outcomes, but the long-term visual acuity outcomes and the potential for Ebola virus RNA to reside in cataract material is unknown. In this study, we reported long-term visual acuity outcomes following MSICS in a cohort of EVD survivors along with histopathology findings from materials collected during surgery. Visual acuity improved over 12-month follow-up with encouraging safety measures. Ebola virus RNA was not detected in cataract and lens capsular tissue analyzed from EVD survivors. This study provides additional assurance regarding the safety and efficacy of cataract surgery, with potential for improved vision for EVD survivors.
| S-EPMC11623560 | biostudies-literature
Project description:A detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections by Marburg marburgvirus (MARV) species were least cross-reactive, while those from survivors of infections by Sudan virus (SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses.
| S-EPMC4979172 | biostudies-literature