Post-EVD symptoms can remain long after recovery and long-term viral persistence in semen is confirmed. The results justify calls for regular check-ups of survivors at least 18 months after recovery.

Between March 23, 2015, and July 11, 2016, we recruited 802 patients, of whom 360 (45%) were male, 442 (55%) were female; 158 (20%) were younger than 18 years. The median age was 28·4 years (range 1·0–79·9, IQR 19·4–39·8). The median delay after discharge was 350 days (IQR 223–491). The most frequent symptoms were general symptoms (324 [40%] patients), musculoskeletal pain (303 [38%]), headache (278 [35%]), depression (124 [17%] of 713 responses), abdominal pain (178 [22%]), and ocular disorders (142 [18%]). More adults than children had at least one clinical symptom (505 [78%] vs 101 [64%], p<0·0003), ocular complications (124 [19%] vs 18 [11%], p=0·0200), or musculoskeletal symptoms (274 [43%] vs 29 [18%], p<0·0001). A positive RT-PCR in semen was found in ten (5%) of 188 men, at a maximum of 548 days after disease onset. 204 (26%) of 793 patients reported stigmatisation. Ocular complications were more frequent at enrolment than at discharge (142 [18%] vs 61 [8%] patients).

In this multidisciplinary observational cohort study, we recruited patients aged 1 year or more in four sites in Guinea (Donka National Hospital, Conakry; Macenta Prefectoral Hospital, Macenta; N'zérékoré Regional Hospital, N'zérékoré; and Forécariah Prefectoral Hospital, Forécariah) following discharge from any Ebola treatment centre in Guinea. Eligible patients had had laboratory-confirmed EVD and had then been declared clear of the virus in the blood. All consenting patients were included, with no exclusion criteria. Trained clinicians assessed patients at enrolment to the cohort, recording clinical symptoms and signs of depression. We did routine blood examinations and examined viral persistence in body fluids using RT-PCR. We did psychological evaluations using questionnaires developed for different age groups. Follow-up is planned to 2 years, and here we present findings at enrolment.

The high number of survivors from the 2013–16 west African outbreak of Ebola virus disease (EVD) has raised several new issues: long-term clinical complications, psychosocial consequences, risks of EVD reactivation, and secondary transmission due to viral persistence in body fluids. We aimed to assess long-term clinical, psychosocial, and viral outcomes in EVD survivors in Guinea.

Guinea was declared Ebola-free on June 1, 2016. Reports from the outbreak documented 3814 cases resulting in 2544 deaths and 1270 survivors.We report here results from an observational multidisciplinary cohort study aiming to assess the long-term clinical, psychological, sociological, and viral outcomes potentially manifest in EVD survivors.

The post-EVD period is characterised by clinical sequelae, delayed viral clearance in immunologically protected sites (semen), psychological distress, and social impact. Its identification and study requires a multidisciplinary approach, challenging fragile health-care systems, and highlights the need for additional laboratories and human health resources allowing regular follow-up and care of EVD survivors.

The results from our large cohort study confirm inferences from a previous review concerning late clinical complications in survivors of EVD, as well as on viral persistence in semen. Our findings are novel in that this study is the first to provide separated results on a large sample of children. Our study is also unique in that it provides a comprehensive, multidisciplinary assessment (clinical, virological in different body fluids, biological, psychological, and sociological) of EVD survivors up to 2 years after discharge from an Ebola treatment centre.

In November, 2014, when this study was proposed, very few data were available on Ebola virus disease (EVD) convalescent patients from past limited outbreaks, and no study had combined a multidisciplinary assessment of health status, virological, clinical, and psycho-sociological status of EVD survivors. We searched PubMed for articles published in any language up to Sept 1, 2016, with the terms “Ebola”, “survivor”, and “sequelae”. We considered the most recent review (published in March, 2016) and the most recent studies in Guinea, Sierra Leone, and Liberia. This literature search on EVD sequelae and possible delayed viral clearance highlighted the need for structured longitudinal research studies of EVD survivors, as well as investment in health-care systems.

When the present cohort study began, few studies had detailed clinical sequelae and viral persistence in body fluids of survivors from the previous outbreaks in central and east Africa. After the 1995 Kikwit outbreak in Democratic Republic of the Congo, two small survivor cohort studiesrevealed that patients frequently had arthralgia, myalgia, abdominal pain, fatigue, anorexia, and late ocular complications. Viral persistence was demonstrated in semen up to 82 and 91 days after disease onset in two patients.After the 2000 Gulu outbreak (Uganda), a short report showed that nearly a quarter of 257 survivors presented with at least one symptom (abdominal pains, vision loss, auditory symptoms, impotence, bleeding, psychological problems, and general weakness).After the 2007 Bundibugyo outbreak (Uganda), a case-control study (49 survivors and 157 contacts) showed that survivors experienced more ocular complications, hearing loss, difficulty swallowing, difficulty sleeping, joint pain, memory loss, or confusion up to 2 years after EVD.Related to the 2013–16 west African outbreak, several surveys of limited size and without control groups have been done in Guinea and Sierra Leone.Musculoskeletal, ocular, and neurological complications were the most frequently noted in EVD survivors.Joint pain was present in 50–77% of convalescent patients and myalgia in 27–50%. Ophthalmological complications were reported in half of the survivors, including 16% of patients who had uveitis. A significant association has been found between the viral load at onset disease and the likelihood of developing uveitis.Skin disorders and alopecia were also reported, as was hearing loss. Neurological complications were also noted, with signs varying widely, from encephalitis to less specific symptoms such as sleeplessness and anxiety.Prevail III,an ongoing study in Liberia, included a control group and found survivors at increased risk of developing ocular, musculoskeletal, and neurological disorders.

Sequelae after Ebola virus disease: even when it's over it's not over.

Since 1976, several limited Ebola virus outbreaks have occurred in central Africa involving various species in the Ebola virus genus (Zaire Ebola, Sudan Ebola, and Bundibugyo Ebola viruses). Mortality of Ebola virus disease (EVD) varies from around 25% for Bundibugyo Ebola virus to 60–90% for Zaire Ebola virus.The 2013–16 west African outbreak infected 28 616 people and caused 11 310 deaths by May 11, 2016, across six countries (Sierra Leone, Liberia, Guinea, Mali, Nigeria, and Senegal).The outbreak has also resulted in the largest number of EVD survivors in history—more than 17 000. The large number of survivors from this unprecedented outbreak has raised new fundamental questions and medical care issues including long-term clinical complications and their treatment, psychosocial consequences, risk of reactivation of the virus and disease, and the risk of viral reintroduction in the community due to sexual transmission.

The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

We present categorical data as n (%) and continuous data as median (IQR). We used χ 2 test or Fisher exact tests for comparisons between adults and children, and a non-parametric Kruskall-Wallis test for cycle threshold values. We analysed symptoms reported by the patients since ETC discharge using Kaplan-Meier curves, with the ETC discharge day as a starting date and the date of first occurrence or the cohort inclusion date as the endpoint. We did additional subgroup analyses to compare patients who had taken part in favipiravir or convalescent plasma trials with patients who had not been included in any trials, and compared clinical signs and biological characteristics between younger (<9 years of age) and older (≥9 years of age) children. Missing data were excluded from the calculations because the objectives were mainly descriptive.

The present analysis focuses on clinical, psychological, sociological, biological, and virological data collected at enrolment until July 11, 2016. We assessed patients at inclusion, and are following up this cohort 1, 3, 6, 9, 12, 18, and 24 months after enrolment. Follow-up data will be published later, and do not contribute to this Article. Data were collected by trained clinicians on a standardised sheet as part of a free clinical examination conducted in the patient's native language. We did routine blood examinations and an RT-PCR on several body fluids (semen, urine, cervicovaginal secretions, breast milk, and saliva). We used three laboratory facilities for the PCR: samples collected from patients recruited from the ETCs in Conakry, Forécariah, and Nzérékoré were analysed either at the joint Dakar Pasteur Institute and “Projet des Fièvres Hémorragiques de Guinée” laboratory in Donka National Hospital or the European West African Mobile Laboratory; samples from patients recruited in Macenta were analysed at the facility deployed by Lyon Pasteur Institute within the ETC of Macenta. All laboratories implemented the standard RealStarFilovirus Screen RT-PCR Kit 1.0 (Altona Diagnostics GmbH, Hamburg, Germany) as well as an additional in-house technique targeting the viral nucleoprotein ( appendix pp 3–4 ). Results were expressed in terms of number of cycles of replication (cycle threshold values).

The Postebogui study is an ongoing prospective multicentre open cohort study. Detailed methods of the study are in the appendix (pp 1–4) . Patients were recruited at four sites in Guinea (Donka National Hospital, Conakry; Macenta Prefectoral Hospital, Macenta; N'zérékoré Regional Hospital, N'zérékoré; and Forécariah Prefectoral Hospital, Forécariah) at any time after discharge from an Ebola treatment centre (ETC) in Guinea. Recruitment started on March 23, 2015, in Conakry and on May 18, 2015, in Macenta, followed a year later by the sites in Forécariah (March 10, 2016) and N'zérékoré (March 24, 2016). The last patient was recruited on July 11, 2016. We included patients aged 1 year or older who had had laboratory-confirmed EVD and had then been declared clear of the virus in the blood before discharge from an ETC. All consenting patients were included, with no exclusion criteria. The overall design of the study was to regularly follow up survivors for clinical, psychosocial, biological, psychological, sociological, and viral evaluation (for questionnaires used, see appendix pp 5–17 ). The protocol was approved by the Research Committee of the National Ebola Response Coordination and the National Ethics and Health Research Committee in Guinea, and French Ethics Committees (INSERM/CEEI, IRD/CCDE). Patients or their parents or guardians provided written informed consent that was translated in all national languages.

Among the 771 respondents to questions on health status, 553 patients (72%) assessed their health status as good or excellent and 218 (28%) as bad or very bad. Occurrence of clinical symptoms was observed in 78 (93%) of the 84 patients who reported feeling sick (11% of the 771 respondents) and in 514 (73%) of the 702 patients who did not report feeling sick (p<0·0001).

501 (64%) of 786 respondents to questions on socioeconomic status had low socioeconomic status, and these individuals were less likely to have depression: of patients who reported on depression, 71 (15%) of 466 patients with low socioeconomic status were depressed, compared with 57 (22%) of 265 patients with high socioeconomic status (p=0·0319). 204 (26%) of 786 respondents reported stigmatisation.

793 (99%) of 802 patients responded to the sociological interview. 644 (81%) of the respondents reported having had cases of EVD in their household. The median number of people with EVD per household was four (IQR 3–7), which included the interviewed patient. Among these cases, the median number of survivors was two (IQR 1–4, ranging to a maximum of 19) and the median number of deaths was two (IQR 1–3, ranging to maximum of 12).

713 (89%) patients—with 551 (69%) patients older than 20 years of age—underwent psychological evaluation. The proportion of patients with an elevated risk of depression ranged from 13% to 21% according to age (overall 124 [17%] of 713 assessed; appendix p 28 ). Nutritional status had no effect on depression: 12 (15%) of 76 patients with a BMI of less than 17 were depressed, and 115 (18%) of 644 patients with a BMI of 17 or more were depressed (p=0·65).

Ten (5%) of 188 male survivors who gave semen samples had a positive RT-PCR for Ebola virus in the first available sample, with a delay since disease onset ranging from 29 to 548 days and cycle threshold value from 26·7 to 40·6. Urine tested positive in two (<1%) of 530 patients tested, one 7 days after ETC discharge (cycle threshold 32·6) and the other 43 days after discharge (cycle threshold 36·0). One (<1%) of 335 saliva samples tested positive (5 days after discharge, cycle threshold 31·6) and none of 191 cervicovaginal fluid samples or 14 breast milk samples tested positive.

186 (26%) patients were anaemic (haemoglobin <11 g/dL) and 12 (2%) patients had haemoglobin less than 8 g/dL. 60 (10%) patients experienced a serum creatinine value greater than 100 μmol/L, but only two (<1%) adults had severe renal injury (serum creatinine value >150 μmol/L), including one adult requiring dialysis. We found no evidence of inflammatory syndrome (elevated C-reactive protein), leucopenia (including CD4 and CD8 lymphopenia), liver enzyme perturbations, or cholesterol or triglyceride imbalance.

Children had fewer overall clinical events than did adults ( table 2 ), with significantly fewer musculoskeletal symptoms and less myalgia, as well as fewer vision disorders. We found no difference in general symptoms, abdominal symptoms, and neurosensory disorders. Comparison of clinical events between children aged 9–18 years and children younger than 9 years of age ( appendix pp 26–27 ) showed older children reported more fatigue (30 [30%] of 101 vs six [11%] of 57, p=0·0057), ocular disorders (16 [16%] vs two [4%], p=0·0194), joint pain (23 [23%] vs three [5%], p=0·0036), neurosensory disorders (49 [49%] vs 18 [32%], p=0·0450), and headache (49 [49%] vs 17 [30%], p=0·0288).

Except for general and ocular symptoms, all symptom frequencies decreased between the acute stage and enrolment in the study ( Table 1 Table 2 ). A comparison of the frequency of symptoms reported at enrolment stratified by their presence or absence during the acute stage of EVD revealed an increased risk of symptoms such as fatigue, myalgia, ocular disorders, and abdominal pain if already present during the acute phase ( appendix p 19 ). At enrolment, neurological disorders were significantly associated with ocular and musculoskeletal symptoms as well as general and abdominal symptoms ( figure 3 appendix p 20 ). Cumulative incidence of signs and symptoms increased regularly until approximately day 600 after discharge and then remained stable, but with a large CI due to the low number of survivors contributing to the denominator after 21 months ( figure 4 appendix pp 21–23 ). Comparison between patients that had received favipiravir or convalescent plasma during the acute stage ( appendix pp 24–25 ) revealed few significant differences, although treated patients experienced more ocular symptoms than did non-treated patients (26 [25%] of 105 vs 116 [17%] of 697, p=0·0539) and more myalgia (25 [24%] vs 86 [12%], p=0·0035).

At enrolment, 606 (76%) patients had post-EVD symptoms ( table 2 ). 324 (40%) patients had general symptoms (fatigue, fever, and anorexia). Ocular disorders were found in 142 (18%) patients: conjunctivitis, vision deficiency (including two cases of legal blindness), and ocular pain were the most frequent. 303 (38%) patients had musculoskeletal symptoms—mainly joint pain and myalgia. 298 patients (37%) had neurosensory disorders, with headache in 278 (35%) patients. 19 patients (2%) were deaf. Abdominal pain was frequent.

58 (7%) of all enrolled patients had participated in the favipiravir trial,and 47 (6%) had received convalescent plasma (in a trialor with a different protocol; table 1 ). The main clinical symptoms during the acute stage were fever, abdominal symptoms, and neurological disorders ( table 1 ), and haemorrhage and dyspnoea—symptoms highlighted in the literature as associated with mortality—were observed in 138 (17%) and 78 (10%) patients, respectively. Adults experienced fatigue, anorexia, diarrhoea, vomiting, myalgia, ocular disorders, auditory symptoms, and neurological disorders (including headache) more often than did children (p<0·05; table 1 ).

Any contact with a sick person or with a confirmed case of Ebola virus disease, excluding contact during the funeral of the deceased, in a care context, or because of accidental blood exposure.

‡ Any contact with a sick person or with a confirmed case of Ebola virus disease, excluding contact during the funeral of the deceased, in a care context, or because of accidental blood exposure.

From March 23, 2015, to July 11, 2016, 804 EVD survivors were invited to participate in the Postebogui cohort study, of whom 802 (>99%) consented and contributed to the analyses. 382 survivors (48%) were enrolled in Conakry, 250 (31%) in Macenta, 116 (14%) in N'zérékoré, and 54 (7%) in Forécariah ( Figure 1 appendix pp 18, 29 ). 360 (45%) patients were male and 442 (55%) were female. The median age at inclusion was 28·4 years (range 1·0–79·9, IQR 19·4–39·8). 158 patients (20%) were children younger than 18 years of age with a median age of 11 years (IQR 6·5–15·1), with 65 (41%) boys and 93 (59%) girls. The median delay between ETC discharge and study enrolment was 350 days (IQR 223–491). The delay was slightly greater in adults (356 days, IQR 228–498) than in children (319 days, 213–457; p=0·0214).

Discussion

4 Kibadi K

Mupapa K

Kuvula K

et al. Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. , 5 Rowe AK

Bertolli J

Khan AS

et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. , 6 Bwaka MA

Bonnet MJ

Calain P

et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. , 7 Rodriguez LL

De Roo a

Guimard Y

et al. Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. , 8 Wendo C Caring for the survivors of Uganda's Ebola epidemic one year on. , 9 Bausch DG Sequelae after Ebola virus disease: even when it's over it's not over. , 10 Clark DV

Kibuuka H

Millard M

et al. Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study. 11 Qureshi AI

Chughtai M

Loua TO

et al. Study of Ebola virus disease survivors in Guinea. , 12 Mattia JG

Vandy MJ

Chang JC

et al. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. , 13 Nanyonga M

Saidu J

Ramsay A

Shindo N

Bausch DG Sequelae of Ebola virus disease, Kenema District, Sierra Leone. , 14 Scott JT

Sesay FR

Massaquoi TA

Idriss BR

Sahr F

Semple MG Post-Ebola syndrome, Sierra Leone. , 15 Tiffany A

Vetter P

Mattia J

et al. Ebola virus disease complications as experienced by survivors in Sierra Leone. , 16 Vetter P

Kaiser L

Schibler M

Ciglenecki I

Bausch DG Sequelae of Ebola virus disease: the emergency within the emergency. , 17 Fallah MP, Prevail III Research Team. A cohort study of survivors of Ebola virus infection in Liberia (PREVAIL III). Annual Conference on Retroviruses and Opportunistic Infections; Boston, MA; Feb 22–25, 2016. 74LB. To our knowledge, this study of a cohort of survivors of the west African outbreak of Zaire EVD is the largest multidisciplinary study of EVD survivors and provides a key contribution to knowledge of post-EVD sequelae. Our results are consistent with observations of general symptoms, arthralgia, myalgia, late ocular complications, hearing loss, psychological and neurological signs, and long viral persistence in semen accrued in previous survivors studiesin central Africa and in studieson the west African outbreak of limited sample sizes. The study also provides a temporal overview of clinical symptoms experienced by survivors with incident events occurring until approximately 600 days post-ETC discharge. Survivors who had experienced a given symptom during acute EVD were at increased risk of presenting with the same symptom at enrolment, illustrating either the persistence or recurrence of symptoms. We found a clear association between neurological disorders and ocular symptoms, as well as with musculoskeletal symptoms, delineating the post-EVD sequelae. Of note, ocular complications were more frequent at enrolment than at discharge, implying that ophthalmological screening should continue long after discharge. Reassuringly, biological assessments showed no inflammatory syndrome or liver cytolysis, and very rare renal injury, which is of interest for patients' long-term prognosis.

12 Mattia JG

Vandy MJ

Chang JC

et al. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. 14 Scott JT

Sesay FR

Massaquoi TA

Idriss BR

Sahr F

Semple MG Post-Ebola syndrome, Sierra Leone. Compared with adults, children had general signs more frequently but experienced specific ocular or musculoskeletal signs less frequently. Psychological distress was common among children. Very few previous studies have included children. One studynoted that 72 patients aged 20 years and younger had lower rates of arthralgia than did adults (19% vs 50%, p=0·004). Anotherincluded 44 survivors in Sierra Leone but did not find any difference in musculoskeletal pain between 11 children and adults. Our study is the first to specifically include a large sample of children, and to demonstrate that post-EVD complications are also present in children but with some differences compared with adults.

21 Deen GF

Knust B

Broutet N

et al. Ebola RNA persistence in semen of Ebola virus disease survivors—preliminary report. , 22 Eggo RM

Watson CH

Camacho A

Kucharski AJ

Funk S

Edmunds WJ Duration of ebola virus RNA persistence in semen of survivors: population-level estimates and projections. , 23 Mate SE

Kugelman JR

Nyenswah TG

et al. Molecular evidence of sexual transmission of Ebola virus. , 24 Saliou SM

Etard J-F

Baize S

et al. New evidence of long-lasting persistence of Ebola virus genetic material in semen of survivors. , 25 Thorson A

Formenty P

Lofthouse C

Broutet N Systematic review of the literature on viral persistence and sexual transmission from recovered Ebola survivors: evidence and recommendations. , 26 Vetter P

Fischer WA

Schibler M

Jacobs M

Bausch DG

Kaiser L Ebola virus shedding and transmission: review of current evidence. 27 Soka MJ

Choi MJ

Baller A

et al. Prevention of sexual transmission of Ebola in Liberia through a national semen testing and counselling programme for survivors: an analysis of Ebola virus RNA results and behavioural data. 28 Diallo B

Sissoko D

Loman NJ

et al. Resurgence of Ebola virus disease in Guinea linked to a survivor with virus persistence in seminal fluid for more than 500 days. 29 Henao-Restrepo AM

Longini IM

Egger M

et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. 26 Vetter P

Fischer WA

Schibler M

Jacobs M

Bausch DG

Kaiser L Ebola virus shedding and transmission: review of current evidence. A positive RT-PCR was observed in semen up to 548 days after ETC discharge. Previous studies have also reported long-term viral persistence in semen, pointing to the potential for sexual transmission.The longest reported persistent positive RT-PCR in semen is 565 days, a duration consistent with our findings.Precisely how long the virus might linger in semen remains unknown. Continued follow-up until viral clearance in semen is clearly needed to reduce risk of sexual transmission from survivors, which has been implicated in post-epidemic cases in spring 2016, in Guinea and resurgence in Liberia.In addition, viral titre in semen might fluctuate, raising the question of how many negative examinations are needed to rule out seminal viral persistence. Health-care officers are also faced with a scarcity of laboratories for viral examinations, and the dispersion and movement of survivors, sometimes to remote places. Prevention relies on condom use. Whether drugs, such as favipiravir, are effective in clearing the virus from the sperm reservoir is still an open question. Vaccination of contacts of survivors has been done and might need modelling to analyse its effect on virus dissemination.We found very few examples of viral persistence in other body fluids (urine, saliva, and breast milk), consistent with previous demonstrations in the literature.

12 Mattia JG

Vandy MJ

Chang JC

et al. Early clinical sequelae of Ebola virus disease in Sierra Leone: a cross-sectional study. 30 Penttila IA

Harris RJ

Storm P

Haynes D

Worswick DA

Marmion BP Cytokine dysregulation in the post-Q-fever fatigue syndrome. Our findings, in combination with results from previous studies, show that post-EVD sequelae are becoming more precisely characterised from a clinical point of view. However, many questions remain concerning mechanisms of pathogenesis. We can hypothesise that the post-EVD sequelae might result from residual dysfunction from direct viral effect, as suggested by the association found between myalgia during the acute stage and myalgia during convalescence. The relationship shown between ophthalmological symptoms,especially uveitis, and viral load at acute stage also suggests a positive correlation between the post-EVD complications and the severity of the acute EVD. Sustained immune activation might also contribute to the post-EVD complications with persistent CD4 and CD8 T cells and circulating pro-inflammatory cytokines as in other post-infection syndromes,warranting further immunological study.

The main limitation of our study is the absence of controls for comparison. Formally, this limitation prevents attribution of post-discharge symptoms to EVD. However, the observation that survivors experiencing a symptom during the acute stage presented more frequently with the same symptom after recovery could suggest a causative role of the virus. Another limitation, given that not all survivors were included in the study, could be a potential bias in our sampling. However, the 802 patients included represent 74% of the Guinean survivors identified by the National Ebola Coordination (weekly report, 17/08/2016; by personal communication), with coverage in urban and rural areas. A few areas were less covered because of concomitant initiatives providing support to the survivors or doing research, particularly in Coyah. Given the size of the study, the high percentage of representation of survivors across the country, and the study's external validity, we feel our results are unlikely to be significantly biased. A third limitation is related to the quality and robustness of the data, partly based on patients' history of symptoms since their ETC discharge and on the difficulty of collecting robust medical data in a post-emergency context in a country such as Guinea with a weak health-care system.

The need to follow-up the survivors using a multidisciplinary approach, which requires qualified laboratories, human health resources, and funding, is a challenge to public health systems that were already fragile before the outbreak and near collapsed after. Follow-up by specialists is clearly needed: given the signs we observed, an ophthalmological examination might be recommended for all convalescent patients, with an adapted follow-up for those with uveitis; mental health teams are needed to take care of survivors' psychological distress; and labs are needed to screen for viral persistence in semen and body fluids. Our results indicate that a close follow-up of all convalescent patients might be warranted for at least 18 months after discharge from ETC, and perhaps even longer depending on whether particular signs have been observed. The Postebogui cohort provides guidance for pragmatic public health recommendations, and indicates the need for further study to better understand the pathogenesis of post-EVD complications.