Risk Factors for Ebola Virus Persistence in Semen of Survivors - Liberia.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically-privileged sites has been implicated in recent outbreaks of Ebola Virus Disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen.

METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with two consecutive negative EBOV semen tests by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at least two weeks apart within 1 year after discharge from the Ebola Treatment Unit (ETU) or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR over one year following ETU discharge or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical exams and blood work.

RESULTS: Compared to early clearers, late clearers were older (median 42.5 years, p = 0.0001) and experienced fewer severe clinical symptoms (median 2, p = 0.006). Late clearers had more lens opacifications (OR 3.9, 95%CI 1.1-13.3, p = 0.03), after accounting for age, higher total serum IgG3 titers (p = 0.007) and increased expression of the HLA-C*03:04 allele (OR 0.14, 95% CI 0.02-0.70, p = 0.007).

CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.