Update #1: SARS-CoV-2 in Semen – Should we be concerned?

Update #1: SARS-CoV-2 in Semen – Should we be concerned?

With the recent report that SARS-CoV-2 is found in semen, the answer now is; We probably should be concerned. This Research Letter published in JAMA Network Open by Li et al. (1) describes their findings in 38 participants who provided a semen specimen. They found

“23 participants (60.5%) had achieved clinical recovery, and 15 participants (39.5%) were at the acute stage of infection. Results of semen testing found that six patients (15.8%) had results positive for SARS-CoV-2, including 4 of 15 patients (26.7%) who were at the acute stage of infection and 2 of 23 patients (8.7%) who were recovering.”

The study, unfortunately, has several limitations. Thirty-eight patients are a small number, and there was no follow up to see when the virus that was found in semen was cleared from semen. Also, the two “recovering” patients were defined as patients that had a “clinical improvement,” which was not defined. They also did not measure the presence of the virus in the nasopharyngeal region at the same time as they test the semen. Other studies have found that SARS-CoV-2 can be found in oropharyngeal secretions for a mean of 9.5 days with a range of 2 to 22 days after symptoms began (2). This same study showed that the virus persisted in stool samples for 2 to 3 days longer than oropharyngeal secretions. Therefore, the two days that Li et al. study followed patients after symptoms started to improve was likely too short. In addition, studies are finding that as many as 20% of patients with the virus are asymptomatic and might be able to transmit the virus for a month or more (3). Therefore, a longitudinal study, following COVID-19 patients over time, measuring the time for viral clearance in several sites, including semen, is needed.

The results of this study also are in contrast to prior studies. I reported in two prior blogs that investigators did not find SARS-CoV-2 in semen or in testicular tissue (4) (NYCryo.com/blog). There is also a recent case report that also did not find SARS-CoV-2 in semen in a COVID-19 positive patient (5). All tests to date have used nasopharyngeal or oropharyngeal swabs to test semen specimens. However, not all body fluids are alike. They contain different proteins that might change the testing results. That is why a viral test must be validated for the body fluid it is being measured in. Validation minimizes the number of false positives (i.e., the test says the patient has the virus but actually the patient is free of the virus) and false negatives (i.e., the test says the patient does not have the virus but actually the patient has the virus). The lack of using validated tests is a possible reason why prior studies did not find the virus in semen (false negative). Conversely, it might also be the reason the Li et al. study found the virus in semen when it might not have been (false positive). To give valid results, the test must be validated for both the virus and the body fluid in which the virus is suspected to be residing.

We still don’t know if the virus in semen can be transmitted to the partner and cause disease. However, given the likely presence of the virus in semen, caution is advised for couples having relations. Especially when the male partner is positive for SARS-CoV-2. In an abundance of caution, until we have more information, abstinence or a barrier contraceptive should be recommended. 

I again refer to an editorial by Feldmann in the New England Journal of Medicine who offers a modified view (6). Dr. Feldmann made a point of differentiating between the presence of a virus detected in a semen sample and the infectivity of that virus. Many viruses are found in semen. However, they are not infectious. A measurement of infectivity is needed. To measure infectivity, you need to know the amount of virus required to cause an infection as well as the pathway that results in infection. For example, if a pathogen such as a virus is in semen but needs to be aerosolized and inhaled to become infectious, then it is less likely to be transmitted to another person. However, other pathogens such as Zika and Ebola can be transmitted by semen to another person through sexual contact. It appears, from the limited information available, that SARS-COV-2 is transmitted through transfer into the lungs by the act of breathing in aerosolized particles containing the virus or transfer of the virus from a surface containing the virus to a person’s mouth or nose even from COVID-19 positive individuals without symptoms (7). Hence, the requirement for hand-hygiene and social distancing. However, Dr. Feldmann feels, it is unlikely that sex, even if the virus is in semen, would be a significant modality of transmission. 

We also don’t know whether SARS-CoV-2 can be transmitted to the developing fetus. A recent case report (8) presented a second-trimester miscarriage in a suspected COBID-19 positive mother. The mother, placenta, and fetus were tested for SARS-CoV-2. The mother and placenta were positive, while the fetus was negative. The suspected cause of the miscarriage was SARS-CoV-2. It is difficult to make broad conclusions from this single case report. However, this report does raise additional concerns and challenges for pregnancies during this pandemic.

As I mentioned in a prior blog, the Society for Assisted Reproductive Technologies (SART) has recommended during this pandemic to stop new assisted reproductive procedures except for urgent cryopreservation (9). This is still good advice in light of the morbidity and potential mortality of this disease to the mother and child, as well as the poorly defined modality of transmission. 

My closing thoughts are updated based on this new information: SARS-CoV-2 are likely found in semen, they can survive the freeze/thaw process of cryopreservation and potentially can be transmitted to the partner and offspring. However, there is presently no data suggesting that SARS-CoV-2 can be transmitted to the partner and offspring from either fresh or cryopreserved semen. Pregnant women and their unborn child are a vulnerable population that should take all precautions for preventing SARS-CoV-2 infection during their pregnancy. Couples considering starting a family during this pandemic might consider being tested for the presence of the virus to make a more informed decision. Cryopreservation of semen should continue during this time with testing the patient for the presence of SARS-CoV-2 and if positive, quarantining the specimens with cryopreserved aliquots available for viral testing once testing of semen and testicular specimens is validated. Patients, as always, should be made aware of the limited data available and that the specimens should be quarantined until validated testing is available, and high-quality evidence regarding the use of SARS-CoV-2 positive specimens is available.

#covid19 #infertility #semen #coronavirus

References:

  1. Li, D., Jin, M., Bao, P., Zhao, W., Zhang, S. (2020). Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019 JAMA Network Open 3(5), 1-3
  2. Ling, Y., Xu, S., Lin, Y., Tian, D., Zhu, Z., Dai, F., Wu, F., Song, Z., Huang, W., Chen, J., Hu, B., Wang, S., Mao, E., Zhu, L., Zhang, W., Lu, H. (2020). Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Chinese Medical Journal 133(9), 1039-1043. https://dx.doi.org/10.1097/cm9.0000000000000774
  3. Pan, Y., Yu, X., Du, X., Li, Q., Li, X., Qin, T., Wang, M., Jiang, M., Li, J., Li, W., Zhang, Q., Xu, Z., Zhang, L. (2020). Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers. The Journal of infectious diseases
  4. Song, C., Wang, Y., Li, W., Hu, B., Chen, G., Xia, P., Wang, W., Li, C., Sha, J., hu, z., Yang, X., Yao, B., Liu, Y.(2020). Detection of 2019 novel coronavirus in semen and testicular biopsy specimen of COVID-19 patients medRxiv https://dx.doi.org/10.1101/2020.03.31.20042333
  5. Paoli, D., Pallotti, F., Colangelo, S., Basilico, F., Mazzuti, L., Turriziani, O., Antonelli, G., Lenzi, A., Lombardo, F. (2020). Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab Journal of Endocrinological Investigation https://dx.doi.org/10.1007/s40618-020-01261-1
  6. Feldmann,H, Virus in Semen and the Risk of Sexual Transmission, New Engl J Medicine, 378;15, 2018
  7. Wei, W., Li, Z., Chiew, C., Yong, S., Toh, M., Lee, V. (2020). Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020 Morbidity and Mortality Weekly Report 69(14), 411-415. https://dx.doi.org/10.15585/mmwr.mm6914e1
  8. Baud, D., Greub, G., Favre, G., Gengler, C., Jaton, K., Dubruc, E., Pomar, L. (2020). Second-Trimester miscarriage in a Pregnant Woman With SARS-CoV-2 Infection JAMA 323(21)https://dx.doi.org/10.1001/jama.2020.7233
  9. https://www.sart.org/news-and-publications/news-and-research/press-releases-and-bulletins/asrm-issues-new-guidance-on-fertility-care-during-covid-19-pandemiccalls-for-suspension-of-most-treatments/

 

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Bruce Gilbert

I am a Urologist/Andrologist practicing in Great Neck, New York for the past 30 years. I am also the Medical and Laboratory Director of New York Cryo, an andrology laboratory and long-term reproductive tissue bank on Long Island. Please send ideas and comments to me at bgilbert@nycryo.com

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