Viral replication and infectivity of monkeypox through semen

With great interest, we read the findings presented by Daniele Lapa and colleagues,¹ showing the successful isolation of monkeypox viral DNA from the seminal fluid of an infected patient. The authors suggested that monkeypox might have a genital reservoir because of the persistent viral shedding in seminal samples, even at low viral copies. These findings could indicate that the current monkeypox outbreak predominantly spreads through sexual transmission, especially after the various reports that estimated that most monkeypox cases were reported among individuals who identify as men who have sex with men. Understanding the mode of transmission could allow for the development of proper interventional approaches to reduce the intensity of the current outbreak.

Monkeypox DNA presence in the seminal fluids might be due to local genital replication or passive diffusion from urine, blood, or genital lesions.² However, the exact mechanism of this event remains controversial in the literature. Although Lapa and colleagues¹ reported that cross-contamination from other sources (blood and urine) is unlikely due to the absence of viral DNA in their specimens, this finding should be interpreted with caution due to some points. First, the finding is based on the results obtained from a single patient. Therefore, an appropriate conclusion is not attainable from this report. Moreover, Noe and colleagues³ showed no growth when culturing the monkeypox virus seminal samples of two patients with monkeypox using VeroE6 cell lines.

Second, previous investigations have detected monkeypox viral DNA in the blood and urine samples of patients with monkeypox. For example, Thornhill and colleagues⁴ reported monkeypox viral DNA-positive PCR results in 7% of blood samples and 3% of urine samples taken from a total of 528 patients with monkeypox. Although these rates are meager, they should be considered, especially because positive blood and urine samples were further reported in other relevant investigations.3, 5 Detecting viral shreds in these samples might suggest potential semen cross-contamination by these particles. Although the authors excluded this possibility in their patient, the sample size is still a major limitation. Third, cross-contamination of viral particles might also occur from genital lesions (eg, exfoliated epithelial cells). However, the authors did not exclude this possibility because their lesion samples were obtained from the head only. According to the evidence from the authors and other studies,³ skin lesions have the most extended viral shedding intervals and highest viral concentrations. For example, Thornhill and colleagues⁴ reported that samples obtained from skin and anogenital regions had the highest positive PCR results (97%) when compared with other samples. Moreover, Tarín-Vicente and colleagues⁶ reported that 99% of skin swabs and 78% of anal swabs were positive in their monkeypox population. These findings indicate the potential ability of these lesions to induce cross-contamination with seminal fluids. However, this was not also specified by Lapa and colleagues.

Furthermore, monkeypox viral detection in semen is not sufficient to indicate its sexual transmission since evidence from previous studies on other viruses that caused viremia and could be detected in semen did not indicate their sexual transmission2, 7 Detecting viral particles within the male reproductive system is commonly secondary to viraemia because the blood–testis barrier is liable to viruses, mainly when local or systemic inflammation occurs.⁸ Viral persistence through the tract is also likely, irrespective of its ability to replicate because the testes can be an immunologically favored site for the virus. Accordingly, we suggest that the current evidence be carefully interpreted until other investigations confirm the findings.

We declare no competing interests.