Effect of COVID-19 on Male Reproductive System – A Systematic Review

Abstract

BackgroundAngiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men.ObjectiveTo provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system.MethodsWe reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included.ResultsWe identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA.ConclusionThe likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father’s infection period.

Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

“…This study was designed to identify potential detrimental effect of the SARS-CoV-2 vaccine by Pfizer on male fertility. Although previous reports demonstrated increased risk of sperm count abnormalities amongst active and recovered SARS-CoV-2 infected patients (Gacci et al, 2021;He et al, 2021;Li et al, 2020), in the present study we could not demonstrate any evidence of adverse effects on semen parameters following COVID-19 vaccination.…”

“…Nonetheless, most studies published so far found no viral traces in the semen of both active disease and recovered patients and a recent review determined the likelihood of SARS-CoV-2 presence in the semen of COVID-19 patients is very small. (Guo et al, 2021;He et al, 2021;Holtmann et al, 2020;Kayaaslan et al, 2020;Pan et al, 2020;Paoli et al, 2020;Song et al, 2020).…”

“…Whether by local infection in the testis, due to fever, or through a general systemic inflammatory environment, detrimental effect of Covid-19 infection to male fertility was found (Gacci et al, 2021;He et al, 2021;Li et al, 2020;Orvieto et al, 2021). In the same previously mentioned study by Li et al, the investigators compared semen analysis parameters of 23 Covid-19 patients with controls and found that 39.1% of those patients (n = 9) had oligozoospermia and 60.9% (n = 14) demonstrated a significant increase in leucocytes in the semen (Li et al, 2020).…”

SARS-CoV-2 spike protein inhibits growth of prostate cancer: a potential role of the COVID-19 vaccine killing two birds with one stone

“…Considering the preferential binding SARS-CoV-2 spike protein has for ACE2 receptors, it is interesting to note that in addition to the high expression of ACE2 receptors in the lungs, several studies have found increased expression of ACE2 receptors in the prostate epithelium, kidneys, and testes, showing that the male genitourinary system may serve as a target-rich environment for SARS-CoV-2 spike protein binding [21][22][23][24]. In their review on the effects of COVID-19 on the male reproductive system, He et al found damage to testicular cells and impaired spermatogenesis and proposed that the pathology is due to both direct interactions of SARS-CoV-2 and ACE2 receptors, as well as systemic inflammatory and immune responses to infection [22].…”

The Effects of Sperm and Seminal Fluid of Immunized Male Mice on In Vitro Fertilization and Surrogate Mother–Embryo Interaction

“…Although these results did not reveal the paternal immune signal per se, they point to possible scenarios for the realization of the effects of antigenic challenge on the reproductive function of men, which includes viral infections. For example, COVID-19 interferes with spermatogenesis, reduces sperm quality in moderately infected patients, and poses health risks to their offspring [43][44][45]. Thus, the IVF model can be effective for studying the effects of antigens of different natures on male reproduction and the development of their offspring.…”