Abstract and Introduction
A unique opportunity to conduct a longitudinal analysis of semen quality in a male subject immediately before, during and after COVID-19 infection, has revealed new insights into the impact of this virus on male reproductive function. A moderate COVID infection that did not require hospitalization resulted in a state of azoospermia that persisted for 4 weeks. Given that the duration of spermatogenesis and epididymal sperm maturation in the human is 78 days, we calculate that a viral attack on the germ line was initiated at or before the patient was symptomatic and may have been signalled by a sudden reduction in sperm count and motility, several weeks earlier. Before the virus had been fully cleared, reinitiation of spermatogenesis occurred as evidenced by spermatozoa reappearing in the ejaculate exhibiting high levels of motility but significant levels of oxidative DNA damage as measured by a modified 8-OHdG assay protocol. These unique data indicate that even a moderate COVID-19 infection is capable of rapidly inducing a state of azoospermia that rapidly reverses as the infection wanes.
The COVID-19 pandemic has been responsible for the loss of over 4.5 million lives since it first broke out of China towards the end of 2019. Initially, it was the elderly or patients with pre-existing medical conditions such as asthma, diabetes, and heart disease who appeared to be particularly vulnerable to viral attack. However, subsequently, the highly infectious Delta variant has proven capable of infecting younger age groups and creating a range of morbidities including the disruption of male fertility.[1,2] The spike protein that gives the COVID-19 corona virus its name, is known to target ACE2 (angiotensin converting enzyme 2), which is highly expressed by several cell types in the testes including Leydig cells, Sertoli cells and the germ line. What little data is currently available, suggests that COVID-19 can be detected in the semen of a small proportion of patients and can certainly gain access to the testes. In this location, it induces both a reduction in testosterone levels and the disruption of semen quality, impacting all aspects of the latter including sperm motility, morphology, and count.[3–6] However, there is a surprising degree of variability between studies, with some analyses reporting a very mild disruption of the semen profile while others report azoospermia in a majority of patients. Some of this disparity may reflect shortcomings in published studies addressing the impact of COVID-19 on male fertility including, (I) the timing of disease onset relative to the semen analysis and (II) a lack of information concerning disease severity.
Most attempts to determine whether COVID-19 infection can influence semen quality have followed a cross sectional study design in which semen quality has been analysed in a group of post-COVID-19 patients, either in isolation or in comparison with a cohort of control subjects that have not suffered infection with this virus. Even when an opportunity has arisen to conduct longitudinal studies of semen quality prior to and following COVID infection, the gaps between semen analysis and the onset of the disease (up to one year) and between recovery and the post infection analysis (at least 3 months) have been considerable. Furthermore, in all studies conducted to date, there has been little opportunity to define the precise relationship between the onset and severity of symptoms and any change in semen quality. In the attached case report, we address this important issue by exploring the unexpected infection of a semen donor within our scientific research program. By carefully monitoring semen quality up to the point where the donor was declared COVID-19 positive and then shortly after he had been declared COVID free, we reveal a surprisingly rapid and severe impact of viral infection on the semen profile, which then reversed within one spermatogenic cycle.
We present the following article in accordance with the CARE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-21-935/rc).
Transl Androl Urol. 2022;11(1):110-115. © 2022 AME Publishing Company