Molecular phenotypes of sex and age specific differences relating to outcome in patients with Ebola virus disease.

Abstract

Ebola virus (EBOV) causes a severe, potentially fatal, disease, with outcome likely related to both viral and host factors. There is a clear correlation between viral load and outcome (survival/death) and inflammatory as well as other cellular pathways are differentially activated in the acute stage between patients who go on to survive versus those who go on to die. Age and sex may influence the course of Ebola virus disease (EVD) with potential differences at the molecular level. To investigate whether there were age and/or sex-specific differences in patients with EVD, previously published data from an RNAseq analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak was stratified according to age/sex of the individual. This was correlated with the outcome of infection. Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalised survivors compared to hospitalized fatal cases, regardless of the sex of the patient. However, aspects of the blood transcriptome/host response differed between females and males and certain age groups at the transcriptomic level. Genes associated with the lymphocyte differentiation pathway decreased in expression level with age in hospitalised fatal cases. However, this was the opposite in hospitalised survivors. From a medical countermeasure perspective, the work indicated that selection of animal models should consider age and sex, depending on the research question, and cellular pathways were identified that could be chemotherapeutically enhanced to promote survival.