COVID-19 and Erectile Dysfunction

Background: The SARS-CoV-2 virus displays a strong impact on the respiratory, digestive, and reproductive systems, and has led to questions about long-term effects. Erectile dysfunction is the inability for a male to achieve or sustain an erection during sexual intercourse, and commonly develops in men due to both physiological and psychologic factors. SARS-CoV-2 can affect the vasculature that surrounds endothelial tissue and thus has raised the question of a possible relationship between SARS-CoV-2 infection and erectile dysfunction (ED). Thus far, no studies have established a relationship between COVID-19 and ED. In this review, we analyze current available data and summarize the concepts regarding the current known relationship between COVID-19 and ED. Such a study might be helpful for urologists and andrologists to manage patients with ED and a history off COVID-19 infection. Method(s): A systematic review was used to analyze the relationship between COVID-19 and ED. A literature search on three databases, Google Scholar, PubMed, and ResearchGate was conducted. Search terms used were COVID-19, erectile dysfunction, and SARS-CoV-2. All available studies were analyzed up to December 2021. Result(s): The COVID-19 pandemic led to a significant increase in male reproductive and sexual health diagnoses, including ED, with numbers showing that COVID-19 increases the chance of developing ED nearly sixfold. Physiological issues were also found in the reproductive system of men who had contracted COVID-19. For example, endothelial progenitor cells were much lower in patients positive with COVID-19 even when compared to men with severe ED who had never contracted COVID-19. However, it is still not clear how consistent it is to find SARS-CoV-2 in the reproductive system as one study showed only two out of five testes were positive for SARS-CoV-2 in the reproductive system and another study showed that there were only 3 out of 26 cases in which the SARS-CoV-2 spike existed in the endothelia of the blood-testis barrier, seminiferous tubules, and sperm of the epididymis. Conclusion(s): Many correlations can be made between COVID-19 and ED. However, future testing and research must be completed to determine a causal relationship between COVID-19 and ED. Copyright © 2022 The Author(s).

Mechanisms of SARS-CoV-2 and Male Infertility: Could Connexin and Pannexin Play a Role?

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication via gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.

COVID-19 disrupts the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins.

OBJECTIVE: Junctional proteins are the most important component of the blood-testis barrier and maintaining the integrity of this barrier is essential for spermatogenesis and male fertility. The present study elucidated the effect of SARS-CoV-2 infection on the blood-testis barrier (BTB) in patients who died from severe acute respiratory syndrome coronavirus 2 (COVID-19) complications. METHODS: In this study, lung and testis tissue was collected from autopsies of COVID-19 positive (n = 10) and negative men (n = 10) and was taken for stereology, immunocytochemistry, and RNA extraction. RESULTS: Evaluation of the lung tissue showed that the SARS-CoV-2 infection caused extensive damage to the lung tissue and also increases inflammation in testicular tissue and destruction of the testicular blood barrier. Autopsied testicular specimens of COVID-19 showed that COVID-19 infection significantly changes the spatial arrangement of testicular cells and notably decreased the number of Sertoli cells. Moreover, the immunohistochemistry results showed a significant reduction in the protein expression of occluding, claudin-11, and connexin-43 in the COVID-19 group. In addition, we also observed a remarkable enhancement in protein expression of CD68 in the testes of the COVID-19 group in comparison with the control group. Furthermore, the result showed that the expression of TNF-α, IL1ß, and IL6 was significantly increased in COVID-19 cases as well as the expression of occludin, claudin-11, and connexin-43 was decreased in COVID-19 cases. CONCLUSIONS: Overall, the present study demonstrated that SARS-CoV-2 could induce the up-regulation of the pro-inflammatory cytokine and down-regulation of junctional proteins of the BTB, which can disrupt BTB and ultimately impair spermatogenesis.

Testis and blood-testis barrier in Covid-19 infestation: role of angiotensin-converting enzyme 2 in male infertility.

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. Evidence shows that SARS-CoV-2 can also affect the urogenital tract. Hence, it should be given serious attention when treating COVID-19-infected male patients of reproductive age group. Other viruses like HIV, mumps, papilloma and Epstein-Barr can induce viral orchitis, germ cell apoptosis, inflammation and germ cell destruction with attending infertility and tumors. The blood-testis barrier (BTB) and blood-epididymis barrier (BEB) are essential physical barricades in the male reproductive tract located between the blood vessel and seminiferous tubules in the testes. Despite the significant role of these barriers in male reproductive function, studies have shown that a wide range of viruses can still penetrate the barriers and induce testicular dysfunctions. Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.