What effect does COVID-19 have on the testes and male fertility? I have been asked this question by many patients and some colleagues. The bottom line is that it is too early to know. However, there is a recent review article that raises some concerns (see full reference below and link to the online paper). This paper, published online, but not yet peer-reviewed, has received much following and comments on Twitter. I usually do not write about papers that have not gone through the rigorous process of peer review, however, due to the amount of discussion surrounding this paper I will summarize their findings and give my thoughts. I will update this blog as more information develops. Please note that I am not endorsing this paper, nor am I advocating undue concern. However, the authors present interesting findings that must undergo review by experts in the field and be supported or refuted by additional research. At present, there is just too little work done on this disease to make recommendations.
Their work is a review paper from the Departments of Urology of the Nanjing Medical University in China, located approximately 300 miles from Wuhan China. Wuhun, was the epicenter of the coronavirus disease in 2019 (abbreviated COVID-19). The virus itself has been named “SARS-CoV-2”. Their review included a total of 146 cases from three prior published papers.
The authors reviewed studies demonstrating that the Angiotensin Converting Enzyme 2 receptor (ACE2) was a major cellular receptor that mediated the entrance of the SARS-CoV-2 into a human cell. ACE2 receptors have been implicated in other severe acute respiratory syndrome coronavirus (SARS). They also noted that a percentage (3% to 10%) of those infected with this virus exhibited kidney damage. They wanted to know if other cell types, that had large numbers of ACE2 receptors, were also affected by this virus. The cells they looked at were renal tubular cells, important for kidney function. They also reviewed two types of cells located in the testis, the Leydig cells, which produce testosterone, the major male hormone and the seminiferous tubule cells which are important in sperm production.
Their results were enlightening.
- The number of receptors in the renal tubular cells was high. The implication was that the ACE2 receptors provided access to the SARS-CoV-2 to these kidney cells and adversely affected kidney function. They suggested monitoring kidney function, especially if the patient is on medications that require modification when kidney function is compromised.
- In their review, they were surprised to find that ACE2 receptors in the seminiferous tubules and Leydig cells were some of the highest in the body. Their takeaway was that the testis is a potential target of SARS-CoV-2. Also, that follow-up evaluation of fertility is important in reproductive-aged men that have had COVID-19. This is particularly concerning in men that had orchitis (ie, an inflammation or infection of the testis) during their COVID-19 infection.
The authors concluded that reproductive function might be compromised in young males recovering from COVID-19. However, there are several concerns with the methodology of this study that need to be kept in mind.
- They reviewed prior work, which identifies a high density of ACE2 receptors in the testis. Although this might imply that the testis would be a target for SARS-CoV-2 it does not document damage that has occurred or provide data on the disease process that might occur.
- Their review included 146 cases in total compared to the 156,433 cases with 5,821 deaths that have occurred at the time of this blog. To make a conclusion based on such a small sample is at best challenging.
Nonetheless, we are only starting to identify the pathogenesis of this disease. We need to gather data continually. Only by the questions we ask, and meticulous collection of data will we get closer to the answers. I will continue to update the impact of COVID-19 on male fertility as we learn more.
C Fan et al, ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection, MEDRXIV 2020. HTTPS://WWW.MEDRXIV.ORG/CONTENT/10.1101/2020.02.12.20022418V10