Understanding the pathogenesis of uveitis in Ebola virus disease survivors: an observational cohort and cross-sectional study protocol for clinical, molecular virologic and immunologic characterisation

INTRODUCTION: The 2013-2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilised local health systems and left thousands of survivors at risk for postacute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humour, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, including the contributions of viral persistence and ocular-specific and systemic immune responses to disease expression. In this study protocol, we outline a multifaceted approach to characterise EVD-associated intraocular inflammation, including the clinical phenotype and complications; the presence of EBOV (or EBOV RNA/antigen) in ocular fluids and tissues; and associated local ocular-specific and peripheral immune responses. METHODS AND ANALYSIS: We use an observational cohort design, which includes EVD survivors and close contacts of EVD survivors (ie, no documented history of EVD), and we propose disease (clinical examination and imaging), as well as molecular, virologic and immunologic characterisation, to meet research objectives. ETHICS AND DISSEMINATION: This study has received Institutional Review Board approval from University of Nebraska Medical Centre, Emory University and Sierra Leone Ministry of Health. Findings will be disseminated through peer-reviewed publications.