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

BackgroundWhether 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

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

BackgroundThere 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).MethodsWe 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.ResultsThis 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.ConclusionWe demonstrated the utility and trade-offs of sequential screening algorithms with RDT or exposure risk assessments as identification strategies for contacts with unrecognized EVD

Challenges of conducting an international observational study to assess immunogenicity of multiple COVID-19 vaccines.

The International Study on COVID-19 Vaccines to Assess Immunogenicity, Reactogenicity, and Efficacy is an observational study to assess the immunogenicity of COVID-19 vaccines used in Democratic Republic of Congo, Guinea, Indonesia, Liberia, Mali, Mexico, and Mongolia. The study, which has enrolled 5,401 adults, is prospectively following participants for approximately two years. This study is important as it has enrolled participants from resource-limited settings that have largely been excluded from COVID-19 research studies during the pandemic. There are significant challenges to mounting a study during an international health emergency, especially in resource-limited settings. Here we focus on challenges and hurdles encountered during the planning and implementation of the study with regard to study logistics, national vaccine policies, pandemic-induced and supply chain constraints, and cultural beliefs. We also highlight the successful mitigation of these challenges through the team's proactive thinking, collaborative approach, and innovative solutions. This study serves as an example of how established programs in resource-limited settings can be leveraged to contribute to biomedical research during a pandemic response. Lessons learned from this study can be applied to other studies mounted to respond rapidly during a global health crisis and will contribute to capacity for stronger pandemic preparedness in the future when there is a crucial need for urgent response and data collection

Design of an observational multi-country cohort study to assess immunogenicity of multiple vaccine platforms (InVITE).

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