Ebola Virus Disease Survivors Research Articles

Beyond survival: unraveling the dynamics of Ebola virus resurgence in Sub-Saharan Africa and the remarkable journey of survivors

Ebola virus disease (EVD) remains a significant public health threat, with sporadic outbreaks occurring in Sub-Saharan Africa. Survivors of EVD may experience various post-infection symptoms, collectively known as post-Ebola virus syndrome (PES), which include chronic arthralgia, uveitis, headache, and psychosocial stressors. In this review, we discuss the persistence of Ebola virus in survivors and its possible role in the reemergence of current outbreaks. We highlight that waning immunity of survivors enhances viral persistence and may lead to viral reactivation and recurrence of disease in previously affected tissues. The delicate equilibrium between diminished immune cell surveillance and limited viral replication may lead to enduring chronic inflammation. Our systematic review, based on an extensive survivor cohort, underscores the importance of continued research and preparedness efforts to combat future outbreaks through adequate surveillance and timely public health interventions. This review serves as a comprehensive guide to understanding the complexities of EVD survivorship, the challenges of PES, and the strategies to mitigate its impact.

Stigmatization of Ebola virus disease survivors in 2022: A cross-sectional study of survivors in Sierra Leone

BackgroundEvidence has demonstrated a high proportion of Ebola virus disease (EVD) survivors experienced stigma due to the disease. This study sought to understand the longer-term effects of stigma encountered by survivors of the 2014–2016 EVD epidemic living in Sierra Leone. MethodsThis was a cross-sectional study of 595 EVD survivors and 403 close contacts (n = 998) from Sierra Leone. Assessments were conducted using a three-part survey between November 2021 to March 2022. We explored the socio-demographic factors associated with stigma experienced by EVD survivors. Findings50·6 % (n = 301) of EVD survivors reported that they continued to experience at least one aspect of stigma. Females were disproportionately affected by stigma, with 45·2 % of females reporting isolation from friends and family compared to 33·9 % of men (p = 0·005). Multivariable logistic regression models revealed those aged 40–44, living rurally, and reporting an acute infection longer than seven days was associated with EVD-related stigma at the time of survey. InterpretationThis study demonstrates stigma is still prevalent among people who survived EVD in 2022. It also identified socio-demographic factors associated with stigma that can be used for targeting interventions. Importantly, this highlights the continued need for EVD survivors to access mental healthcare and social support systems well after disease recovery. FundingThis study was funded by the Canadian Institutes for Health Research (Grant no. PJT-175098. JK is funded by a Tier 2 Canada Research Chair in the Molecular Pathogenesis of Emerging and Re-Emerging Viruses. SS is funded by a Tier 2 Canada Research Chair in Program Science and Global Public Health.

Prevalence and Factors Related to Post-traumatic Stress Disorder and Depression Symptoms Among Children and Adolescents Survivors and Orphans of Ebola Virus Disease in Democratic Republic of the Congo Eastern Regions During the COVID-19 Pandemic

PurposeAlthough previous studies have shown a high prevalence of mental health problems among adult Ebola virus disease survivors, no studies have yet been conducted on mental health problems among children and adolescents in affected regions. Consequently, the current study aimed to examine the prevalence and factors associated with depression and post-traumatic stress disorder (PTSD) among children and adolescent survivors and orphans by utilizing a cross-sectional survey following the 2018–2020 epidemic in Eastern Democratic Republic of the Congo. MethodsA total of 146 survivors (mean age = 13.62, standard deviation [SD] = 2.50, 49.32% female), 233 orphans (mean age = 13.18, SD = 2.96, 53.32% female), and 34 orphan-survivor participants (mean age = 13.39, SD = 2.87, 44.12% female) were recruited. Participants completed measures assessing depression and PTSD symptoms, traumatic experiences, and stigma related to Ebola and COVID-19. ResultsThe prevalence of depression and PTSD symptoms was 87.32% and 44.42%, respectively. Results showed significant differences in depression and PTSD symptoms between orphan-survivors (100% and 97.06%), survivors (90.21% and 75.86%), and orphans (83.48% and 16.52%; χ2(2) = 9.02; p = .011 and χ2(2) = 168.85; p < .001). Experience of traumatic events, Ebola stigmatization, and COVID-19 stigmatization positively predicted depression and PTSD symptoms. The regression models explained 61%–72% of the variance of depression and PTSD. DiscussionThe results reveal that the Ebola virus disease and its associated grief severely jeopardize the mental health of children and adolescents in affected regions. Despite the relative paucity of resources, intervention programs may be helpful to minimize associated stigma and promote psychological support.

Visual acuity and vision-related quality of life outcomes following cataract surgery in Ebola virus disease survivors.

The objectives of this study were to assess relationships between vision-related quality of life (QoL) and visual acuity (VA) in Ebola virus disease (EVD) survivors after cataract surgery in the Ebola Viral Persistence in Ocular Tissues and Fluids (EVICT) Study. EVD survivors with undetectable Ebola virus (EBOV) ribonucleic acid in their aqueous humour were eligible to receive manual small-incision cataract surgery (MSICS). Among those that received surgery, assessments of VA and vision-related QoL were assessed pre-and post-cataract surgery. VA was converted from units on a tumbling 'E' chart to the logarithm of the minimal angle of resolution VA (logMAR VA). Vision-related QoL was assessed using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Linear regression was used to evaluate the associations between VA and vision-related QoL. P = 0.05 was considered statistically significant for all analyses. Thirty-four EVD survivors underwent cataract surgery in the EVICT study. Before MSICS, the mean logMAR VA was 2.24 (standard deviation [SD]: 0.98), and the mean NEI-VFQ-25 composite score was 54 (SD: 15); however, there was no significant association between the pre-surgery measurements (average difference in VA/10 unit increase in NEI-VFQ-25: -0.04, 95% confidence interval (CI): -0.33-0.26, P = 0.80). There was a significant improvement in logMAR VA after MSICS (mean: 1.6, P < 0.001), but there was no significant change in the NEI-VFQ-25 composite (-0.87, 95% (CI): -10.32-8.59, P = 0.85). None of the subscales showed significant improvements (P > 0.12 for all); however, the magnitude of the mean change for distance activities (6.65), near activities (6.76), general vision (-7.69), social functioning (-9.13) and colour vision (13.33) met the criteria for a clinically meaningful difference (4-6). In the subset with paired measurements (n = 16), there were no significant association changes in logMAR VA and NEI VFQ-25 composite scores (P > 0.12 for all). Following cataract surgery, VA in EVD survivors improved, but these improvements were not reflected in NEI VFQ-25 composite scores or specific subscales; however, the small sample size limits generalizability absent more research. Differences in sociocultural context and activities that affect the QoL in resource-limited areas may contribute to the limitations seen with NEI VFQ-25. In addition, better eye dominance could contribute to any lack of association as NEI VFQ-25 evaluates vision as a whole. Further, assessment of factors contributing to improved QoL may help to define the impact of vision health in varied environments.

Pregnancy in people who have survived Ebola virus disease

Pregnancy in people who have survived Ebola virus disease

Long-Term Decrease in Intraocular Pressure in Survivors of Ebola Virus Disease in the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Study.

Survivors of Ebola virus disease (EVD) experience decreased intraocular pressure (IOP) relative to unaffected close contacts during the first year of convalescence. Whether this effect persists over time and its relationship to intraocular pathology are unclear. We sought to determine whether IOP remained lower in survivors of EVD over 4 years of follow-up and to identify associated risk factors. Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III is a 5-year, longitudinal cohort study of survivors of EVD and their close contacts and is a collaboration between the Liberian Ministry of Health and the United States National Institutes of Health. Participants who enrolled in PREVAIL III at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 who underwent comprehensive ophthalmic evaluation annually for 5 consecutive visits. Intraocular pressure was measured at each visit by a handheld rebound tonometer using sterile tips. Comparisons are made between antibody-positive survivors and antibody-negative close contacts. Intraocular pressure, measured in mmHg, at each study visit. Of 565 antibody-positive survivors and 644 antibody-negative close contacts enrolled in the study at baseline, the majority of participants returned annually, with 383 (67.8%) and 407 (63.2%) participants, respectively, presenting for the final study visit at a median of 60 months after symptom onset. A sustained, relative decrease in IOP was observed in survivors relative to close contacts, with mean difference of-0.72 mmHg (95% confidence interval [CI]-1.18 to-0.27) at the final study visit. This difference remained constant throughout the study period (P= 0.4 for interaction over time). Among survivors, physical examination findings of vitreous cell and OCT findings of vitreous opacities both demonstrated a significant association with decreasedIOP at baseline (P < 0.05 for both). After adjusting for such factors, the difference throughout the follow-up (-0.93 mmHg, 95% CI,-1.23 to-0.63) remained significant. Survivors of EVD experienced a sustained decrease in IOP relative to close contacts over a 5-year period after EVD. The results highlight the importance of considering long-term sequelae of emerging infectious diseases within a population. Proprietary or commercial disclosure may be found after the references.

Survivors of Ebola virus disease exhibit elevated levels of autoantibodies

Abstract Survivors of Ebola virus disease (EVD) report a wide range of symptoms following recovery from acute viral infection, but underlying mechanisms are unclear. Many of these symptoms, collectively termed Post-Ebola Syndrome (PES), occur in the absence of detectable virus and resemble symptoms associated with autoimmune disease, such as arthralgia and myalgia, suggesting that EVD survivors may be experiencing a virus-induced autoimmune response. Studies in mice have shown that mice develop autoantibodies (autoAb) against HSP-60 and double stranded (ds) DNA that can bind to host tissues following Ebola virus (EBOV) infection. To determine if human EVD survivors also develop autoAb that may be associated with PES development, we profiled the humoral immune response of 354 survivors and 195 household contacts (HHC) from the 2014–2016 outbreak in Sierra Leone. Using Systems Serology, we measured the levels of antibodies against common autoantigens and found that EVD survivors had elevated levels of autoAb against dsDNA, HSP-60, IFNα, and citrullinated histone compared to HHC. As a subset of HHC were seropositive for EBOV glycoprotein (GP)-specific antibodies, separation of HHC into GP-seropositive and seronegative groups showed that the levels of autoAb in GP-seropositive HHC were elevated compared to GP-seronegative HHC, strongly suggesting that exposure/infection to EBOV tracks with presence of autoAb. As antibodies can activate innate immune cells via the antibody Fc domain, current studies are focused on analyzing the innate effector response mediated by these autoAb in EVD survivors and seropositive HHC. Together, our study highlights the potential role of autoAb in long-term sequelae associated with survival from EVD.

Demographic Factors Associated with Presenting for Eye Evaluation in the Partnership for Research on Vaccines and Infectious Diseases in Liberia III Natural History Study of Ebola Virus Disease.

Survivors of Ebola virus disease (EVD) are at risk for ocular complications after infection. We sought to identify demographic factors associated with the likelihood to present for eye examination among Ebola survivors enrolled in a longitudinal natural history study of EVD. The Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Ebola natural history study is a 5-year study that seeks to identify long-term sequelae of EVD, including ocular sequelae. All survivors enrolled in the PREVAIL parent study from June 2015 to March 2016 were asked to return for comprehensive eye examination through June 2016. Logistic regression was conducted using self-reported survivor status, age, gender, and distance from the hospital as covariates. A total of 1448 subjects enrolled in the parent PREVAIL III longitudinal cohort during the defined window, of which 1375 (95.0%) followed up for baseline eye examination. Ebola survivors (635/661, 96.1%) and adult close contacts (727/767, 94.8%) demonstrated a comparable likelihood for presenting for eye examination (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.36-1.28). In an adjusted model, age over 50 (OR 10.2, 95% CI 1.35-77.3) and living outside Montserrado County (OR 0.18, 95% CI 0.10-0.33) were associated with the likelihood of presenting for a baseline comprehensive eye examination. Most EVD survivors and their close contacts who enrolled during the study window presented for eye examinations. Older participants and those who lived closer to clinical facilities were most likely to present. Focused strategies accounting for these factors may assist with organizations planning survivor care in the setting of EVD.

Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes.

Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood-retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors.

Persistent intraocular Ebola virus RNA is associated with severe uveitis in a convalescent rhesus monkey

Despite increasing evidence that uveitis is common and consequential in survivors of Ebola virus disease (EVD), the host-pathogen determinants of the clinical phenotype are undefined, including the pathogenetic role of persistent viral antigen, ocular tissue-specific immune responses, and histopathologic characterization. Absent sampling of human intraocular fluids and tissues, these questions might be investigated in animal models of disease; however, challenges intrinsic to the nonhuman primate model and the animal biosafety level 4 setting have historically limited inquiry. In a rhesus monkey survivor of experimental Ebola virus (EBOV) infection, we observed and documented the clinical, virologic, immunologic, and histopathologic features of severe uveitis. Here we show the clinical natural history, resultant ocular pathology, intraocular antigen-specific antibody detection, and persistent intraocular EBOV RNA detected long after clinical resolution. The association of persistent EBOV RNA as a potential driver of severe immunopathology has pathophysiologic implications for understanding, preventing, and mitigating vision-threatening uveitis in EVD survivors.

Long-term consequences of food insecurity among Ebola virus disease-affected households after the 2013-2016 epidemic in rural communities of Kono District, Sierra Leone: A qualitative study.

The 2013-2016 Ebola virus disease (EVD) epidemic caused food insecurity during and immediately following local outbreaks in Sierra Leone, but longer-term effects are less well described, particularly among households with no EVD survivors. We conducted a qualitative sub-study in July 2018 in Kono District, Sierra Leone to understand the impact of food insecurity on EVD-affected households. Using data from a community-based cohort, we compiled a list of all households, within the sampled communities in Kono District, that had at least one EVD case during the epidemic. We used purposive sampling to recruit 30 households, inclusive of 10 households with no EVD survivors, to participate in the study. The research team conducted open-ended, semi-structured interviews with the head of each household. All 30 interviews were transcribed, translated, and analyzed using comparative content analysis consistent with a grounded theory approach. Most household members were facing persistent food insecurity as direct or indirect consequences of the EVD epidemic, regardless of whether they did or did not live with EVD survivors. Three major themes emerged as drivers and/or mitigators of EVD-related food insecurity. Financial instability and physical health complications were drivers of food insecurity in the population, whereas support provided by NGOs or governmental agencies was observed as a mitigator and driver of food insecurity after its removal. Among the EVD-households reporting long-term support through jobs and educational opportunities, there was sustained mitigation of food insecurity. EVD-affected households with and without survivors continue to face food insecurity three years after the EVD epidemic. Provision of support was a mitigator of food insecurity in the short term, but its removal was a driver of food insecurity in the longer term, suggesting the need for longer-term transitional support in affected households.

Relationship between selenium deficiency and vulnerability to ebolavirus disease in beni, drc

In Ebola patients, selenium aids in regulating blood clotting and possibly assist in coagulopathy properties of the Ebola haemorrhagic fever. Therefore, the objectives of this study were to determine the Selenium levels of people living in Beni, DRC and whether there is an association between Ebola vulnerability and selenium deficiency.This was a case control study with cases being Ebola virus disease survivors and controls were their contact persons during the time of infection. Students t-test were computed to determine if there exist a significant difference in the population means selenium levels in the case group and control group. Logistic regression analysis model was fitted into the data to determine the association between selenium deficiency and vulnerability to EVD adjusting for demographic and socio-economic factors.The mean difference in selenium levels of non - survivors was higher than that of survivors. A t-test conducted suggested that this difference in mean was statistically significant with p-value less than 0.05 (0.00181). The odds of getting infected by Ebola while having normal selenium levels, is 3.47 (confidence interval, 1.30 - 10.21) times higher than when one has high selenium levels after adjusting for all other covariates as mentioned above.There was a statistically significant relationship between Ebola vulnerability and selenium deficiency.

Statistical methodologies for evaluation of the rate of persistence of Ebola virus in semen of male survivors in Sierra Leone.

The 2013-2016 Ebola virus (EBOV) outbreak in West Africa was the largest and most complex outbreak ever, with a total number of cases and deaths higher than in all previous EBOV outbreaks combined. The outbreak was characterized by rapid spread of the infection in nations that were weakly prepared to handle it. EBOV ribonucleic acid (RNA) is known to persist in body fluids following disease recovery, and studying this persistence is crucial for controlling such epidemics. Observational cohort studies investigating EBOV persistence in semen require following up recently recovered survivors of Ebola virus disease (EVD), from recruitment to the time when their semen tests negative for EBOV, the endpoint being time-to-event. Because recruitment of EVD survivors takes place weeks or months following disease recovery, the event of interest may have already occurred. Survival analysis methods are the best suited for the estimation of the virus persistence in body fluids but must account for left- and interval-censoring present in the data, which is a more complex problem than that of presence of right censoring alone. Using the Sierra Leone Ebola Virus Persistence Study, we discuss study design issues, endpoint of interest and statistical methodologies for interval- and right-censored non-parametric and parametric survival modelling. Using the data from 203 EVD recruited survivors, we illustrate the performance of five different survival models for estimation of persistence of EBOV in semen. The interval censored survival analytic methods produced more precise estimates of EBOV persistence in semen and were more representative of the source population than the right censored ones. The potential to apply these methods is enhanced by increased availability of statistical software to handle interval censored survival data. These methods may be applicable to diseases of a similar nature where persistence estimation of pathogens is of interest.

Post-Ebola Symptoms 7 Years After Infection: The Natural History of Long Ebola.

Lingering symptoms have been reported by survivors of Ebola virus disease (EVD). There are few data describing the persistence and severity of these symptoms over time. Symptoms of headache, fatigue, joint pain, muscle pain, hearing loss, visual loss, numbness of hands or feet were longitudinally assessed among participants in the Liberian Ebola Survivors Cohort study. Generalized linear mixed effects models, adjusted for sex and age, were used to calculate the odds of reporting a symptom and it being rated as highly interfering with life. From June 2015 to June 2016, 326 survivors were enrolled a median of 389 days (range 51-614) from acute EVD. At baseline 75.2% reported at least 1 symptom; 85.8% were highly interfering with life. Over a median follow-up of 5.9 years, reporting of any symptom declined (odds ratio for each 90 days of follow-up = 0.96, 95% confidence interval [CI]: .95, .97; P < .0001) with all symptoms declining except for numbness of hands or feet. Rating of any symptom as highly interfering decreased over time. Among 311 with 5 years of follow-up, 52% (n = 161) reported a symptom and 29% (n = 47) of these as highly interfering with their lives. Major post-EVD symptoms are common early during convalescence and decline over time along with severity. However, even 5 years after acute infection, a majority continue to have symptoms and, for many, these continue to greatly impact their lives. These findings call for investigations to identify the mechanisms of post-EVD sequelae and therapeutic interventions to benefit the thousands of effected EVD survivors.

Identifying Paucisymptomatic or Asymptomatic and Unrecognized Ebola Virus Disease Among Close Contacts Based on Exposure Risk Assessments and Screening Algorithms.

There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for paucisymptomatic or asymptomatic Ebola virus (EBOV) infection and unrecognized EBOV disease (EVD). We used serostatus and self-reported postexposure symptoms from a cohort study to classify contact-participants as having no infection, paucisymptomatic or asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, or high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with or without rapid diagnostic testing (RDT) or exposure assessments. This analysis included 990 EVD survivors and 1909 contacts, of whom 115 (6%) had paucisymptomatic or asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (adjusted odds ratio, 3.5 [95% confidence interval, 2.4-4.9]). To identify contacts with unrecognized EVD who test negative by the WHO case definition, the sensitivity was 96% with RDT (95% confidence interval, 91%-99%), 87% with high-risk exposure (82%-92%), and 97% with intermediate- to high-risk exposures (93%-99%). The proportion of false-positives was 2% with RDT and 53%-93% with intermediate- and/or high-risk exposures. We demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD.

The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone

BackgroundGlobally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world’s population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors.Methodology and principal findingsEVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p < 0.001). Additionally, survivors were more likely to have bilateral hearing loss of a mixed etiology. Logistic regression revealed that the presence of any symptoms of middle or inner ear (p < 0.001), eye (p = 0.005), psychiatric (p = 0.019), and nervous system (p = 0.037) increased the odds of developing hearing loss.Conclusions and significanceThis study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics.

Risk Factors for Ebola Virus Persistence in Semen of Survivors in Liberia.

Long-term persistence of Ebola virus (EBOV) in immunologically privileged sites has been implicated in recent outbreaks of Ebola virus disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work. Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .007). Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

Clinical sequelae among individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease in Liberia: a longitudinal cohort study

SummaryBackgroundWhether or not individuals with pauci-symptomatic or asymptomatic Ebola virus infection and unrecognised Ebola virus disease develop clinical sequelae is unknown. We assessed current symptoms and physical examination findings among individuals with pauci-symptomatic or asymptomatic infection and unrecognised Ebola virus disease compared with Ebola virus disease survivors and uninfected contacts.MethodsBetween June 17, 2015, and June 30, 2017, we studied a cohort of Ebola virus disease survivors and their contacts in Liberia. Surveys, current symptoms and physical examination findings, and serology were used to characterise disease status of reported Ebola virus disease, unrecognised Ebola virus disease, pauci-symptomatic or asymptomatic Ebola virus infection, or no infection. We pre-specified findings known to be differentially prevalent among Ebola virus disease survivors versus their contacts (urinary frequency, headache, fatigue, muscle pain, memory loss, joint pain, neurological findings, chest findings, muscle findings, joint findings, abdominal findings, and uveitis). We estimated the prevalence and incidence of selected clinical findings by disease status.FindingsOur analytical cohort included 991 reported Ebola virus disease survivors and 2688 close contacts. The median time from acute Ebola virus disease onset to baseline was 317 days (IQR 271–366). Of 222 seropositive contacts, 115 had pauci-symptomatic or asymptomatic Ebola virus infection and 107 had unrecognised Ebola virus disease. At baseline, prevalent findings of joint pain, memory loss, muscle pain, and fatigue were lowest among those with pauci-symptomatic or asymptomatic infection or no infection, higher among contacts with unrecognised Ebola virus disease, and highest in reported survivors of Ebola virus disease. Joint pain was the most prevalent finding, and was reported in 434 (18%) of 2466 individuals with no infection, 14 (12%) of 115 with pauci-symptomatic or asymptomatic infection, 31 (29%) of 107 with unrecognised Ebola virus disease, and 476 (48%) of 991 with reported Ebola virus disease. In adjusted analyses, this pattern remained for joint pain and memory loss. Survivors had an increased odds of joint pain compared with unrecognised Ebola virus disease contacts (adjusted odds ratio [OR] 2·13, 95% CI 1·34–3·39); unrecognised Ebola virus disease contacts had an increased odds of joint pain compared with those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 1·89, 95% CI 1·21–2·97). The adjusted odds of memory loss was more than four-times higher among survivors than among unrecognised Ebola virus disease contacts (adjusted OR 4·47, 95% CI 2·41–8·30) and two-times higher among unrecognised Ebola virus disease contacts than in those with pauci-symptomatic or asymptomatic infection and uninfected contacts (adjusted OR 2·05, 95% CI 1·10–3·84). By 12 months, prevalent findings had decreased in the three infected groups.InterpretationOur findings provide evidence of post-Ebola virus disease clinical sequelae among contacts with unrecognised Ebola virus disease but not in people with pauci-symptomatic or asymptomatic Ebola virus infection.FundingNational Cancer Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Severe Anxiety and PTSD Symptoms Among Ebola Virus Disease Survivors and Healthcare Workers in the Context of the COVID-19 Pandemic in Eastern DR Congo.

Ebola virus disease (EVD) survivors and healthcare workers (HCWs) face stress, fear, and stigma during the COVID-19 pandemic that can induce severe symptoms of anxiety and post-traumatic stress disorder (PTSD). We examined the prevalence and factors related to severe PTSD and anxiety symptoms, using a representative sample of survivors of the 2018–2020 EVD epidemic in DR Congo in comparison HCWs. Five hundred sixty-three participants (55.25% women, 309 survivors, 202 HCWs, and 52 HCWs and survivors) completed questionnaires assessing anxiety, PTSD, exposure to EVD and COVID-19, stigmatization related to EVD and COVID-19, interpersonal traumas, social support. During the COVID-19 pandemic, 45.6 and 75.0% of survivors and HCWs reported severe symptoms of PTSD and anxiety. Significant difference was observed among the three groups for both PTSD (53.7% survivors, 37.1% HCWs, and 30.8% HCWs-survivors, χ2= 18.67, p < 0.0001) and anxiety (88.3% survivors, 56.9% HCWs, and 65.4% HCWs- survivors, χ2= 67.03, p < 0.0001). Comorbidity of severe PTSD and anxiety symptoms was 42.3% between the three groups. Results revealed that exposure to EVD (b = 0.53; p = 0.001; b = 0.12; p = 0.042), EVD-related stigmatization (b = 0.14; p = 0.018; b = 0.07; p = 0.006), COVID-19-related stigmatization (b = 0.22; p < 0.0001; b = 0.08; p = 0.0001) and social support (b = −0.30; p < 0.0001; b = −0.14; p < 0.0001) predicted severe PTSD and anxiety symptoms. The last models explained 63.8 and 56.4% of the variance of PTSD and anxiety. Symptoms of PTSD and anxiety are common among EVD survivors and HCWs during the COVID-19 pandemic. Culturally-sensitive programs that address stigma are necessary to mitigate the cumulative effects of EVD and the COVID-19 pandemic on EVD survivors and HCWs.

Ebola Survivors are not at Increased Risk for Gynecologic Surgeries

As the result of multiple signs and symptoms, and complications observed among survivors of the Ebola virus disease (EVD), there is an assumption that survivors might experience perturbations within their clotting parameters. This may eventually lead to increased bleeding time, predisposing them to increased risk for surgical complications. This study aimed to comparatively review specific intra-operative parameters such as uterine fibroids and polyps among a number of EVD survivors and non survivors undergoing elective gynecologic surgeries at Redemption Hospital, a tertiary specialized referral hospital located within one of the EVD hotspots, in Liberia from January to October 2016. A case-control study was conducted wherein cases were referred from the Partnership for = Research on Vaccines and Infectious Diseases in Liberia (PREVAIL), an EVD clinical trial platform, while controls were sampled from the general patient population, at Redemption Hospital. The controls were matched based on age, employment status and parity. All surgeries were performed by single surgeon based on a surgical checklist that included designated intra- and post-operative parameters. Statistical analysis such as counts, percentiles, confidence intervals and relative risks were performed to assess the differences between the cases and controls, respectively. Survivors were between the ages of 42 years and 44 years for controls with an average interval between discharge from the Ebola Treatment Unit (ETU) and surgical intervention of greater than one year. The median duration of surgical procedure was 60 minutes and blood loss of 250 ml in both groups. Besides the relative risks (RR) of receiving antibiotics for more than 3 days of 1.5 (85.7% vs. 57.1%) and hospitalization of more than 7 days of 0.25 (14% vs. 57%) for survivors as compared to controls, most of the indicators were not significantly different. The findings revealed that EVD survivors who present with benign tumors such as uterine fibroids, polyps, or adenomyosis, requiring elective uterine surgery such as myomectomy and/or hysterectomy are generally not at increased risk of surgical complications because most of the indicators (hospitalization, blood loss, antibiotics, etc.) were not significantly different between the two groups. Findings from this study may potentially revise the approaches used by gynecologists and general surgeons during encounters and/or interventions with patient(s) concerning emerging infectious diseases (EIDs)