Risk Factors for Ebola Virus Persistence in Semen of Survivors in 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 2 consecutive negative EBOV semen test results by real-time reverse-transcription polymerase chain reaction (rRT-PCR) ≥2 weeks apart within 1 year after discharge from the Ebola treatment unit or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR >1 year after discharge from the Ebola treatment unit or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical examinations and blood work.
Results: Compared with early clearers, late clearers were older (median, 42.5 years; P < .001) and experienced fewer severe clinical symptoms (median 2, P = .006). Late clearers had more lens opacifications (odds ratio, 3.9 [95% confidence interval, 1.1-13.3]; P = .03), after accounting for age, higher total serum immunoglobulin G3 (IgG3) titers (P = .005), and increased expression of the HLA-C*03:04 allele (0.14 [.02-.70]; P = .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.
Competing Interests: Potential conflicts of interest. A. Kofman reports support for attending meetings and/or travel from the CDC Foundation. R. S. B. reports $11 000 in grants or contracts from the University of Mississippi Medical Centre and $7500 in contracts or grants from the Federation University Centre for Health Transformation and Innovation, both unrelated to this work; a registration fee waiver ($650) in support of attending the Australian Society for Microbiology 2022 meeting; World Intellectual Property Organization patent WO2019060840, (Removing Interfering Host Nucleic Acids for Molecular Parasite Detection; granted 28 March 2019; patent royalties to the CDC Division of Parasitic Diseases and Malaria); unpaid participation on the Surveillance Cross-cutting Subgroup of the World Health Organization Neglected Tropical Disease Diagnostic Technical Advisory Group, unpaid participation as a member of the Strongyloides subgroup of the WHO Technical Advisory Group on Schistosomiasis and Transmitted Helminthiases, and unpaid participation at a WHO policy meeting with Dora Buonfrate of Ospidale Sacra Cuore (Italy) and Antonio Montresor of the WHO (Diagnostic Methods for the Control of Strongyloidiasis; 29 September 2020); and leadership or fiduciary roles with Strongyloides Australia (as vice president), the Australian Society for Parasitology Education Committee, and the Australian Society for Infectious Diseases Zoonosis Special Interest Group. S. H. H. reports consulting fees paid to the author from Leavitt Associates; support for attending meetings and/or travel from their employer (University of Nebraska Medical Center); patents planned, issued or pending (none related to this work); participation on the advisory board of the HHS National Coordinator of IT; and ownership of stock or stock options (none related to this article). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.)