madman
Super Moderator
Abstract
The Coronavirus 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 160 million infections and 3.5 million deaths globally. Men are disproportionately affected by COVID-19, having more severe disease with higher mortality rates than women. Androgens have been implicated as the underlying cause for more severe disease, as the androgen receptor has been noted to upregulate the cell surface receptors that mediate viral cell entry and infection. Unfortunately, despite testosterone’s potential role in COVID-19 prognosis, androgen deprivation therapy is neither protective nor treatment for COVID-19. Interestingly, the male reproductive organs have been found to be vulnerable in moderate to severe illness, leading to reports of erectile dysfunction and orchitis. COVID-19 viral particles have been identified in penile and testis tissue, both in live patients who recovered from COVID-19 and post-mortem men who succumbed to the disease. Although sexual transmission remains unlikely in recovered men, moderate to severe COVID-19 infection can lead to germ cell and Leydig cell depletion, leading to decreased spermatogenesis and male hypogonadism. The objective of this review is to describe the impact of SARS-CoV-2 on male reproductive health. There are still many unanswered questions as to the specific underlying mechanisms by which COVID-19 impacts male reproductive organs and the long-term sequelae of SARS-CoV-2 on male reproductive health.
Introduction
Coronavirus 2019 (COVID-19) is a novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in Wuhan China in December 2019. Since then, COVID-19 has spread globally and has infected more than 166 million people, and caused more than 3.5 million deaths around the world (1,2). Although there is no difference in the percentage of men and women diagnosed with COVID-19, large-scale, multi-country statistical analyses have shown that men suffer from higher disease severity and mortality rate compared with women (3,4). While the underlying reason for worse prognosis of COVID-19 in men has not been fully elucidated, it does appear that male gender is a risk factor for severe infection worldwide.
Researchers have been attempting to discover the underlying mechanisms causing the disproportionate impact of COVID-19 on men. The underlying mechanisms for viral entry of SARS-CoV-2 could be influenced by androgens, which are well known to have higher serum concentrations in men (5). The potential role of androgens in COVID-19 severity has been investigated, and medical castration has even been explored as a potential treatment(6,7). The male reproductive organs have also been described as being vulnerable to infection believed to be due to direct viral entry. Erectile dysfunction has been reported after COVID-19 recovery and viral particles have even been documented in penile tissue up to 7 months after infection (8). Epididymoorchitis has been reported in almost a quarter of infected men, raising concerns about SARS-CoV-2’s ability to enter the testis, break down the testis-blood barrier and affect spermatogenesis, and potentially be spread through sexual contact (9,10). In this review, we will briefly describe the underlying mechanisms for SARS-CoV-2’s entry into human cells and describe how this may lead to worse infection in men, review the role of androgens in COVID19 infection and implications for treatment, and discuss the virus’ impact on male reproductive organs in order to comprehensively highlight the current evidence of SARS-CoV-2’s impact on male reproductive health.
*Viral Mechanism of Entry
*COVID-19 Infection differences in Men and Women
*Androgens and SARS-CoV-2
*COVID-19’s Impact on Male Reproductive Organs Tract
-Penis and Erectile Dysfunction
-Prostate and Seminal Vesicles
-Testis and Epididymis
*Potential for Sexual Transmission and Effect on Male Fertility
Conclusion
There are still many questions as to why the COVID-19 pandemic has disproportionately affected men, leading to more severe disease and worse mortality rates than women. In addition to men generally having more comorbid conditions than women, higher androgen levels have been identified as a potential mechanism for viral cell entry. The ability for the AR to upregulate ACE2 and TMPRSS2 genes could be an underlying reason for worse disease severity; however, the data is mixed on whether clinical differences exist amongst men on TRT and ADT. Furthermore, despite extremely low levels detected of both ACE2 and TMPRSS2 in reproductive organs such as the testis, there have been higher than expected rates of orchitis and spermatogenesis impairment amongst men with moderate to severe COVID-19, suggesting that there may be another mechanism by which the virus impacts male reproductive health. As the long-term effects of infection in males are not yet available, it is important for men who have overcome COVID-19 with concerns about potential consequences of the disease to seek medical care. Future research is needed to elucidate the sequelae of infection, develop methods to decrease SARS-CoV-2’s impact on male reproductive health, and address the long-term consequences of severe disease.
The Coronavirus 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 160 million infections and 3.5 million deaths globally. Men are disproportionately affected by COVID-19, having more severe disease with higher mortality rates than women. Androgens have been implicated as the underlying cause for more severe disease, as the androgen receptor has been noted to upregulate the cell surface receptors that mediate viral cell entry and infection. Unfortunately, despite testosterone’s potential role in COVID-19 prognosis, androgen deprivation therapy is neither protective nor treatment for COVID-19. Interestingly, the male reproductive organs have been found to be vulnerable in moderate to severe illness, leading to reports of erectile dysfunction and orchitis. COVID-19 viral particles have been identified in penile and testis tissue, both in live patients who recovered from COVID-19 and post-mortem men who succumbed to the disease. Although sexual transmission remains unlikely in recovered men, moderate to severe COVID-19 infection can lead to germ cell and Leydig cell depletion, leading to decreased spermatogenesis and male hypogonadism. The objective of this review is to describe the impact of SARS-CoV-2 on male reproductive health. There are still many unanswered questions as to the specific underlying mechanisms by which COVID-19 impacts male reproductive organs and the long-term sequelae of SARS-CoV-2 on male reproductive health.
Introduction
Coronavirus 2019 (COVID-19) is a novel viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in Wuhan China in December 2019. Since then, COVID-19 has spread globally and has infected more than 166 million people, and caused more than 3.5 million deaths around the world (1,2). Although there is no difference in the percentage of men and women diagnosed with COVID-19, large-scale, multi-country statistical analyses have shown that men suffer from higher disease severity and mortality rate compared with women (3,4). While the underlying reason for worse prognosis of COVID-19 in men has not been fully elucidated, it does appear that male gender is a risk factor for severe infection worldwide.
Researchers have been attempting to discover the underlying mechanisms causing the disproportionate impact of COVID-19 on men. The underlying mechanisms for viral entry of SARS-CoV-2 could be influenced by androgens, which are well known to have higher serum concentrations in men (5). The potential role of androgens in COVID-19 severity has been investigated, and medical castration has even been explored as a potential treatment(6,7). The male reproductive organs have also been described as being vulnerable to infection believed to be due to direct viral entry. Erectile dysfunction has been reported after COVID-19 recovery and viral particles have even been documented in penile tissue up to 7 months after infection (8). Epididymoorchitis has been reported in almost a quarter of infected men, raising concerns about SARS-CoV-2’s ability to enter the testis, break down the testis-blood barrier and affect spermatogenesis, and potentially be spread through sexual contact (9,10). In this review, we will briefly describe the underlying mechanisms for SARS-CoV-2’s entry into human cells and describe how this may lead to worse infection in men, review the role of androgens in COVID19 infection and implications for treatment, and discuss the virus’ impact on male reproductive organs in order to comprehensively highlight the current evidence of SARS-CoV-2’s impact on male reproductive health.
*Viral Mechanism of Entry
*COVID-19 Infection differences in Men and Women
*Androgens and SARS-CoV-2
*COVID-19’s Impact on Male Reproductive Organs Tract
-Penis and Erectile Dysfunction
-Prostate and Seminal Vesicles
-Testis and Epididymis
*Potential for Sexual Transmission and Effect on Male Fertility
Conclusion
There are still many questions as to why the COVID-19 pandemic has disproportionately affected men, leading to more severe disease and worse mortality rates than women. In addition to men generally having more comorbid conditions than women, higher androgen levels have been identified as a potential mechanism for viral cell entry. The ability for the AR to upregulate ACE2 and TMPRSS2 genes could be an underlying reason for worse disease severity; however, the data is mixed on whether clinical differences exist amongst men on TRT and ADT. Furthermore, despite extremely low levels detected of both ACE2 and TMPRSS2 in reproductive organs such as the testis, there have been higher than expected rates of orchitis and spermatogenesis impairment amongst men with moderate to severe COVID-19, suggesting that there may be another mechanism by which the virus impacts male reproductive health. As the long-term effects of infection in males are not yet available, it is important for men who have overcome COVID-19 with concerns about potential consequences of the disease to seek medical care. Future research is needed to elucidate the sequelae of infection, develop methods to decrease SARS-CoV-2’s impact on male reproductive health, and address the long-term consequences of severe disease.
