MAY 09, 2020 -- SARS-CoV-2, the virus that causes COVID-19, may be present in the semen of patients with COVID-19, both those recovering and those with acute disease, according to a small study published online today in JAMA Network Open.
However, several experts caution that the researchers only tested for viral components and that the findings do not demonstrate infectivity. "I am not aware of any reports of infection transmitting sexually, so the risk here, even if the study is verified at a larger scale, is very limited," said Ian Jones, PhD, professor of virology, University of Reading, United Kingdom.
Other experts note that the published article is short on information about methodology and context. "I'm not saying they are wrong, but they are shy on details," said Maureen Ferran, PhD, associate professor of biology, Rochester Institute of Technology, New York. She notes that although the authors say they used reverse-transcription polymerase chain reaction (RT-PCR) to detect viral RNA from nasal swabs to confirm infection, they don't say what they did to detect virus in semen, leaving readers to assume they also used RT-PCR to test those samples.
A spokesperson from the JAMA press office has clarified that the authors did use RT-PCR to detect viral RNA in semen; the authors did not respond to multiple email requests for comment.
"It is peer-reviewed, but everyone is trying to get everything out so fast that some things are suffering," Ferran continued. She noted that she was surprised the authors did not mention other studies that have shown conflicting results.
In the newly reported study, SARS-CoV-2 was detected in semen from 6 (15.8%) of 38 patients tested. All of the patients had confirmed COVID-19.
The finding may have implications for the prevention and control of COVID-19, note the study authors, led by Diangeng Li, PhD, from the Chinese People's Liberation Army General Hospital, Beijing, China.
"Owing to the imperfect blood-testes/deferens/epididymis barriers, SARS-CoV-2 might be seeded to the male reproductive tract, especially in the presence of systemic local inflammation," the authors write.
"Even if the virus cannot replicate in the male reproductive system, it may persist, possibly resulting from the privileged immunity of testes," Li and colleagues write.
If further research shows that SARS-CoV-2 is sexually transmitted, then this may be critical in the prevention of transmission, they note. "Abstinence or condom use might be considered as a preventive means for these patients," they suggest.
Commenting on the study, Allan Pacey, PhD, FRCOG, professor of andrology at the University of Sheffield, United Kingdom, acknowledges that this opens up the possibility that one route of infection may be through sexual contact, although this has not been confirmed.
He told Medscape Medical News that although the findings appear robust, they are at odds with a recent study published in Fertility and Sterility that found no evidence of the virus in semen in a similar number of men (n = 34), suggesting a need for more research. "From my own experience ... I can confirm that there are a number of methodological challenges to overcome in order to truly establish the source of an infection with virus or bacteria within the male reproductive tract, and moreover that any DNA/RNA represents enough virus or bacteria which are sufficient to cause infection by sexual contact."
That point was echoed by Walter D. Cardona Maya, PhD, microbiologist and expert in semen evaluation at the University of Antioquia, Medellín, Colombia. "[T]his infection with SARS-CoV-2 is very similar to other viral infections that could be transmitted by semen and therefore during sexual intercourse," he told Medscape Medical News.
He added that similar results were reported in 2003 for SARS-CoV, the virus that causes severe acute respiratory syndrome. On the basis of that study and other articles, as a whole, "the evidence shows that with regards to COVID-19 asymptomatic patients, it is very important to consider this alternative infection route. The possibility of transferring the virus via couples, and perhaps with an effect on fertility and offspring, should be evaluated," he said. Cardona Maya recently wrote a commentary, SARS-CoV-2 and the Testis: Similarity With Other Viruses and Routes of Infection, which discusses this in more detail.
Viral Presence in Semen
It is not uncommon to find viruses in semen, and it might be more common than currently understood, note Li and colleagues in the new study. To date, 27 viruses have been associated with viremia in human semen. "Traditional non–sexually transmitted viruses should not be assumed to be totally absent in genital secretions," they write.
The researchers initiated the observational study after recognizing that little was known about SARS-CoV-2 in semen. The virus has been detected in stool, the gastrointestinal tract, saliva, and urine samples.
To address this research gap, men with laboratory-confirmed COVID-19 who were undergoing treatment at Shangqiu Municipal Hospital, China, were asked to provide a semen sample for SARS-CoV-2 testing. Of the 50 patients, 38 were able to provide a viable sample.
The authors note that SARS-CoV-2 viral RNA was present in recovering patients as well as those with acute infections. They report that 23 of the patients who provided a semen sample had achieved clinical recovery. Of these, samples from two (8.7%) tested positive for SARS-CoV-2. Of the 15 participants with acute disease, samples from four patients (26.7%) were positive for SARS-CoV-2.
The authors write that "there was no significant difference between negative and positive test results for patients by age, urogenital disease history, days since onset, days since hospitalization, or days since clinical recovery."
They add that avoidance of contact with the patient's saliva and blood may not be enough, because the fact that SARS-CoV-2 survived in a recovering patient's semen suggests it is likely that the virus could infect others.
Conflicting Studies Highlighting Need for Further Work
Several groups have noted that the testes have high expression of the angiotensin-converting enzyme 2 (ACE2) receptor, which the virus uses for cell entry. One study, posted on a preprint server on April 17 but not peer-reviewed, showed that clearance of the virus is delayed in men. The authors, led by Aditi Shastri, MBBS, of Albert Einstein College of Medicine, New York City, wrote, "High expression of ACE2 in testes raises the possibility that testicular viral reservoirs may play a role in viral persistence in males and should be further investigated."
In contrast, an observational study of 12 patients in recovery, none of whom had had severe COVID-19 pneumonia, found that all the patients tested negative for SARS-Cov-2 RNA in semen samples. Another patient, aged 67 years, who died tested negative for viral RNA in a testicular biopsy. The study, published as a letter in Biology of Reproduction, concluded that no viral RNA was found in the semen or testicular biopsy specimen but that further work was needed to confirm the finding.
The study authors have disclosed no relevant financial relationships. Pacey is chairman of the advisory committee of the UK National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, and trustee of the Progress Educational Trust (all unpaid). He has recently conducted work for the World Health Organization, the British Broadcasting Corporation, and Purple Orchid Pharma (paid consultancy with all monies going to University of Sheffield) and is co-applicant on a research grant from the Medical Research Council. The other commentators have disclosed no relevant financial conflicts.