BACKGROUND Multiple health problems have been reported in survivors of Ebola virus disease (EVD). Attribution of these problems to the disease without a control group for analysis is difficult. METHODS We enrolled a cohort of EVD survivors and their close contacts and prospectively collected data on symptoms, physical examination findings, and laboratory results. A subset of participants underwent ophthalmologic examinations. Persistence of Ebola virus (EBOV) RNA in semen samples from survivors was determined. RESULTS A total of 966 EBOV antibody–positive survivors and 2350 antibody-negative close contacts (controls) were enrolled, and 90% of these participants were followed for 12 months. At enrollment (median time to baseline visit, 358 days after symptom onset), six symptoms were reported significantly more often among survivors than among controls: urinary frequency (14.7% vs. 3.4%), headache (47.6% vs. 35.6%), fatigue (18.4% vs. 6.3%), muscle pain (23.1% vs. 10.1%), memory loss (29.2% vs. 4.8%), and joint pain (47.5% vs. 17.5%). On examination, more survivors than controls had abnormal abdominal, chest, neurologic, and musculoskeletal findings and uveitis. Other than uveitis (prevalence at enrollment, 26.4% vs. 12.1%; at year 1, 33.3% vs. 15.4%), the prevalence of these conditions declined during follow-up in both groups. The incidence of most symptoms, neurologic findings, and uveitis was greater among survivors than among controls. EBOV RNA was detected in semen samples from 30% of the survivors tested, with a maximum time from illness to detection of 40 months. CONCLUSIONS A relatively high burden of symptoms was seen in all participants, but certain symptoms and examination findings were more common among survivors. With the exception of uveitis, these conditions declined in prevalence during follow-up in both groups. Viral RNA in semen persisted for a maximum of 40 months.

Background Ebola virus RNA persists in the semen of male Ebola survivors for months to years after the acute infection and male-to-female sexual transmission of the virus is well documented. We investigated whether remdesivir can safely reduce persistence of seminal Ebola virus RNA. Methods We recruited men with persistent seminal Ebola RNA in Liberia and in Guinea. Participants were randomized 1:1 to receive intravenous remdesivir (GS-5734; Gilead Sciences) or matching placebo administered once daily by intravenous infusion over one hour on 5 consecutive days. Stratification was by country and number of positive (1 or 2) pre-enrollment semen tests. The study team was blinded to treatment group allocation and specific liver related lab results. We evaluated the difference in mean assay negativity rate (ANR), i.e., the proportion of negative tests for each participant in each group in the treatment (days 1-28) and follow-up (months 2-6) phases, on an intention-to-treat basis. ClinicalTrials.gov NCT02818582; closed. Results We enrolled 38 men from July 2016 through June 2018. The mean treatment phase ANRs were 85% (sd=24%) and 76% (sd=30%) in the remdesivir and placebo arms, respectively (p=0.270). The mean follow-up phase ANRs were 96% (sd=10%) and 81% (sd=29%) in the remdesivir and placebo arms, respectively (p=0.041). The five-day remdesivir regimen was well-tolerated with no safety concerns. Conclusions In this small trial, remdesivir 100mg/day for five days safely reduced the presence of Ebola virus RNA in the semen of Ebola survivors two to six months after administration. A larger follow up study is necessary to confirm results.

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In response to the COVID-19 pandemic, COVID-19 vaccines have been developed, and the World Health Oraganization (WHO) has granted emergency use listing to multiple vaccines. Studies of vaccine immunogenicity data from implementing COVID-19 vaccines by national immunization programs in single studies spanning multiple countries and continents are limited but critically needed to answer public health questions on vaccines, such as comparing immune responses to different vaccines and among different populations.

Background There is limited evidence to evaluate screening algorithms with rapid antigen testing and exposure assessments as identification strategies for pauci-/asymptomatic Ebola virus (EBOV) infection and unrecognized Ebola virus disease (EVD). Methods We used serostatus and self-reported post-exposure symptoms from a cohort study to classify contact-participants as no infection, pauci-/asymptomatic infection, or unrecognized EVD. Exposure risk was categorized as low, intermediate, and high. We created hypothetical scenarios to evaluate the World Health Organization (WHO) case definition with and without rapid antigen testing (RDT) or exposure assessments. Results This analysis included 990 EVD survivors and 1,909 contacts, of which 115 (6%) had pauci-/asymptomatic EBOV infection, 107 (6%) had unrecognized EVD, and 1,687 (88%) were uninfected. High-risk exposures were drivers of unrecognized EVD (aOR 3.5, 95%CI: 2.4-4.9). To identify contacts with unrecognized EVD who test-negative by WHO case definition, sensitivity was 96% with RDT (95% CI: 91-99), 87% with high-risk exposure (95% CI: 82-92), and 97% with intermediate-to-high-risk exposures (95% CI: 93-99). The proportion of false-positives was 2% with RDT and 53-93% with intermediate- and/or high-risk exposures. Conclusion We demonstrated utility and trade-offs of sequential screening algorithms with RDTs or exposure risk assessments as identification strategies for contacts with unrecognized EVD.