Molecular Phenotypes of Sex- and Age-Specific Differences Relating to Outcome in Patients With Ebola Virus Disease

Ebola virus causes a severe, potentially fatal disease with the outcome likely related to viral and host factors. There is a clear correlation between viral load and outcome (survival/death), and inflammatory and other cellular pathways are differentially activated in the acute stage between patients who survive and those who die. Age and sex may influence the course of Ebola virus disease with potential differences at the molecular level.

To investigate whether there were age- and/or sex-specific differences in patients with Ebola virus disease, previously published data from an RNA sequencing analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak were stratified according to age and sex. This was correlated with the outcome of infection.

Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalized survivors as compared with 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 hospitalized fatal cases. However, this was the opposite in hospitalized 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.