Is Andes hantavirus sexually transmitted?

A number of posts on social media have suggested that Andes hantavirus, which most recently caused an outbreak on the MV Hondius, is sexually transmitted. These claims are based on a 2023 paper (Presence and Persistence of Andes Virus RNA in Human Semen). Let’s take a look at the data and see what conclusions can be made.

The paper presents a follow-up of a male patient who recovered from hantavirus pulmonary syndrome six years previously. Viral RNA was detectable intracellularly in semen samples throughout the complete study period of almost six years, without integration into the host genome, as demonstrated by the loss of signal after RNase treatment. The key virological controls are solid: they excluded genomic integration, localized the RNA to cells (not seminal plasma), and genome sequence analysis early and late after infection revealed only two single-nucleotide variants and one deletion, suggesting limited replication. The sequencing data is actually one of the most interesting pieces: very few mutations over ~6 years is consistent with a depot of largely non-replicating RNA, analogous to what has been described in Ebola survivors.

Why no infectious virus was recovered
The inability to isolate infectious virus is important. Cell lines known to be productively infected with Andes virus were used, so this is not the problem. Perhaps levels of infectious virus were too low for detection. The study demonstrated a long-lasting, strong neutralizing antibody response using pseudovirions expressing the ANDV glycoprotein. Neutralizing antibodies would presumably suppress replication, which is consistent with both the paucity of mutations and the failure to recover infectious virus. Whether this means the genome is truly defective/inert or simply held in check is an open question.

Corroboration from other studies?
This is a single case report. ANDV viral RNA persistence was identified and characterized in this long-term follow-up study conducted in Switzerland on an imported case, and based on these findings, the authors raised the possibility of ANDV transmission via sexual contact, although this route had not been previously documented. There are no independently published cases confirming the persistence of this duration in semen. What exists is a broader framework suggesting that this phenomenon is not inherently surprising. Long-term persistence of viral RNA has been known for decades, particularly in immunologically privileged sites such as the brain, eyes, and testes, with measles/SSPE being an early example; more recently, Ebola virus persistence in the eye and brain of convalescent patients has further emphasized this phenomenon. The testes as a sanctuary site has now been documented for filoviruses as well: Sudan virus persists in the seminiferous tubules (specifically in Sertoli cells) of nonhuman primate survivors, accompanied by tissue damage and inflammatory cell invasion.

Conclusions
•This is a single case, n=1. It’s a fascinating case report but cannot tell us the frequency of this phenomenon among ANDV survivors. Systematic follow-up studies of convalescent patients would be needed.
•RNA does not equal infectious virus. The failure to culture virus is critical, and the minimal sequence evolution argues against ongoing replication. Whether the RNA could serve as a template under any circumstances (e.g., immunosuppression) is unknown.
•Sexual transmission is plausible but undemonstrated. ANDV is the only hantavirus for which person-to-person transmission has been documented, though the precise routes of transmission have not been identified: inhalation of droplets or aerosolized virions are the most likely routes, and transmission via sexual contact has not been documented.
•The study raises an important public health question about convalescent ANDV patients, analogous to recommendations made after the 2014–2016 Ebola epidemic regarding semen testing and safe sex guidance for survivors.

In short, the finding is novel, technically well-supported within its single-case scope, biologically plausible given precedents in other viruses, but not yet corroborated by independent studies.

An interesting question is how many different viral genomes can be found in semen? A systematic review published in The Lancet Microbe did the accounting. The analysis identified 22 viruses capable of persisting in human semen after acute infection, with 9 showing evidence of sexual transmission. The 22 viruses confirmed in semen included, among others, Ebola, Zika, Marburg, mpox, West Nile, dengue, yellow fever, adenovirus, and SARS-CoV-2. Replication-competent virus was demonstrated for adenovirus, dengue, Ebola, and Zika, among others.

Three additional viruses were detected elsewhere in the male reproductive tract but not in semen itself: Crimean-Congo hemorrhagic fever virus, hantavirus causing hemorrhagic fever with renal syndrome (HFRS), and Heartland virus. Notably, the review covered HFRS-causing hantaviruses — but not ANDV, which is the outlier that causes HCPS rather than HFRS, and has now been added to this landscape by the Zust 2023 paper.

Duration of persistence varied enormously: Ebola had the longest viral persistence, detected 988 days after ETU discharge and 965 days after illness onset. The maximum detection of Zika was 941 days after onset, but its median persistence was only 57 days. The shortest duration was 8 days for Kyasanur Forest disease, with West Nile at 22 days and dengue at 37 days.

An important nuance on sexual transmission vs. RNA detection
Detection of viral genomes in semen tends to be more common among viruses that are typically not sexually transmitted, such as certain adenoviruses, bunyaviruses, flaviviruses, hepadnaviruses, herpesviruses, paramyxoviruses, and retroviruses. And for Zika specifically, only 4% of ZIKV RNA-positive semen samples were found to be infectious, and infectivity was observed only in samples obtained within 30 days after illness onset with viral loads above 7.0 log₁₀ RNA copies per mL, a useful reminder that RNA detection and transmission risk are very different questions.

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