Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study.

Background: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence.

Methods: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis.

Dysglycaemia in Ebola virus disease: a retrospective analysis from the 2018 to 2020 outbreak.

Background: Ebola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units.

Methods: We conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC.

Rhabdomyolysis, Acute Kidney Injury, and Mortality in Ebola Virus Disease: Retrospective Analysis of Cases From the Eastern Democratic Republic of the Congo, 2019.

Background: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined.

Methods: This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo.

Results: An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1-11]).

SARS-CoV-2 seroprevalence in vaccine-naïve participants from the Democratic Republic of Congo, Guinea, Liberia, and Mali.

Objectives: The InVITE study, starting in August 2021, was designed to examine the immunogenicity of different vaccine regimens in several countries including the Democratic Republic of Congo, Guinea, Liberia, and Mali. Prevaccination baseline samples were used to obtain estimates of previous SARS-CoV-2 infection in the study population.

Methods: Adult participants were enrolled upon receipt of their initial COVID-19 vaccine from August 2021 to June 2022.

Development of the PREDS score to predict in-hospital mortality of patients with Ebola virus disease under advanced supportive care: Results from the EVISTA cohort in the Democratic Republic of the Congo.

Background: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS.

Methods: In this prospective cohort (NCT04815175), patients were recruited during the 10 EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs).

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.

Virus kinetics and biochemical derangements among children with Ebolavirus disease.

Background: A paucity of data is available on virologic and biochemical characteristics of paediatric Ebolavirus disease (EVD), compared to adults.

Methods: We conducted a retrospective chart review of children (<16 years old) and a comparator group of young adults (16-44 years) from two treatment centres during the 2018-2020 EVD epidemic in Eastern Democratic Republic of the Congo. Statistical methods included chi-squared and Fisher's exact tests (dichotomous and categorical variables), Mann-Whitney U-test (continuous variables), multivariable linear regression (for determinants of admission viral load), linear mixed-effects models (for analysis of longitudinal viral load), and Cox proportional hazard models (to examine risk factors for mortality).

Review: Insights on Current FDA-Approved Monoclonal Antibodies Against Ebola Virus Infection.

The unprecedented 2013-2016 West Africa Ebola outbreak accelerated several medical countermeasures (MCMs) against Ebola virus disease (EVD). Several investigational products (IPs) were used throughout the outbreak but were not conclusive for efficacy results. Only the Randomized Controlled Trial (RCT) on ZMapp was promising but inconclusive.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

Background: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z).

Methods: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

Background: The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).

Methods: In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community.

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

Background: The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD.

Methods: We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV).