madman
Super Moderator
Purpose: A pilot study to describe histopathological features of the penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED).
Materials and Methods: Penile tissue was collected from patients undergoing surgery for penile prosthesis for severe ED. Specimens were obtained from two men with a history of COVID-19 infection and two men with no history of infection. Specimens were imaged with TEM and H&E staining. RT-PCR was performed from corpus cavernosum biopsies. The tissues collected were analyzed for endothelial Nitric Oxide Synthase (eNOS, a marker of endothelial function) and COVID-19 spike-protein expression. Endothelial progenitor cell (EPC) function was assessed from blood samples collected from COVID-19 (+) and COVID-19 (-) men.
Results: TEM showed extracellular viral particles ~100 nm in diameter with peplomers (spikes) near penile vascular endothelial cells of the COVID-19 (+) patients and absence of viral particles in controls. PCR showed the presence of viral RNA in COVID-19 (+) specimens. eNOS expression in the corpus cavernosum of COVID-19 (+) men was decreased compared to COVID-19 (-) men. Mean EPC levels from the COVID-19 (+) patients were substantially lower compared to mean EPCs from men with severe ED and no history of COVID-19.
Conclusions: Our study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our results also suggest that widespread endothelial cell dysfunction from COVID-19 infection can contribute to ED. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection leads to ED.
INTRODUCTION
Coronavirus disease 2019 (COVID-19) was originally observed in China, in December 2019, and since then has grown into a global pandemic [1]. Studies have shown that the ability of COVID-19 to enter cells relies heavily on the presence of angiotensin-converting enzyme-2 (ACE-2). Before binding to ACE-2 receptors, viral spike proteins must be primed by cellular proteases, specifically, transmembrane protease serine 2 (TMPRSS-2) [2]. Therefore, COVID-19 appears to affect cells and tissues that co-express ACE-2 and TMPRSS-2 [3]. Interestingly, both the ACE-2 receptor and TMPRSS-2 genes are expressed on endothelial cells and likely explains why COVID-19 infection produces widespread endothelial dysfunction. Electron microscopy has demonstrated the presence of COVID-19 viral elements in endothelial cells of affected organs, such as the lung, heart, and kidney. These findings raise the question as to whether erectile tissue in the penis, rich in endothelial-lined blood vessels, can also be subject to widespread endothelial dysfunction caused by COVID-19. Here we describe the histopathological features of the penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED).
DISCUSSION
In this report, we provide evidence of COVID-19 in the human penis long after the initial infection. Our study also suggests that endothelial dysfunction from COVID-19 infection can contribute to resultant ED. Vascular integrity is necessary for erectile function, and endothelial damage associated with COVID-19 is likely to affect the penile vascular flow, resulting in impaired erectile function. We could not detect viral protein in penis tissue by immunohistology, possibly due to comparably low viral RNA load in the penis. This result was not surprising since recent studies show that COVID-19 isolation is unlikely from samples with low RNA loads [4]. H&E staining from our specimens did not show significant results compared to previous studies in which COVID-19 infection caused mild to moderate accumulation of lymphomonocytic inflammatory cells in a perivascular or subendothelial distribution [5]. Based on the current findings we can draw two hypotheses about how the SARS-CoV-2 virus can lead to the ED. First, similar to other complications related to COVID-19, ED can be the result of systemic infection resulting in widespread endothelial dysfunction. This is supported by our findings of endothelial dysfunction seen in men with COVID and ED. Second, we can also hypothesize that the worsening of these patient’s ED can be due to the virus’ presence within the cavernosal endothelium itself. This is best supported by our findings with TEM. The primary limitation of this study was the sample size (n=2) and lack of objective quantification of erectile function before and after infection for patients and controls. For now, the history of COVID-19 should be included in the work-up of ED and positive findings should be investigated accordingly. Patients should be aware of the potential complication of post-COVID-19 ED. Any changes observed in erectile function after infection should be followed up with the appropriate specialist for treatment and to help further investigation into the condition. Future studies are needed to validate the effects of this virus on sexual function.
CONCLUSION
This study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our study also suggests that widespread endothelial cell dysfunction from COVID-19 infection can contribute to resultant erectile dysfunction. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection can lead to ED.
Materials and Methods: Penile tissue was collected from patients undergoing surgery for penile prosthesis for severe ED. Specimens were obtained from two men with a history of COVID-19 infection and two men with no history of infection. Specimens were imaged with TEM and H&E staining. RT-PCR was performed from corpus cavernosum biopsies. The tissues collected were analyzed for endothelial Nitric Oxide Synthase (eNOS, a marker of endothelial function) and COVID-19 spike-protein expression. Endothelial progenitor cell (EPC) function was assessed from blood samples collected from COVID-19 (+) and COVID-19 (-) men.
Results: TEM showed extracellular viral particles ~100 nm in diameter with peplomers (spikes) near penile vascular endothelial cells of the COVID-19 (+) patients and absence of viral particles in controls. PCR showed the presence of viral RNA in COVID-19 (+) specimens. eNOS expression in the corpus cavernosum of COVID-19 (+) men was decreased compared to COVID-19 (-) men. Mean EPC levels from the COVID-19 (+) patients were substantially lower compared to mean EPCs from men with severe ED and no history of COVID-19.
Conclusions: Our study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our results also suggest that widespread endothelial cell dysfunction from COVID-19 infection can contribute to ED. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection leads to ED.
INTRODUCTION
Coronavirus disease 2019 (COVID-19) was originally observed in China, in December 2019, and since then has grown into a global pandemic [1]. Studies have shown that the ability of COVID-19 to enter cells relies heavily on the presence of angiotensin-converting enzyme-2 (ACE-2). Before binding to ACE-2 receptors, viral spike proteins must be primed by cellular proteases, specifically, transmembrane protease serine 2 (TMPRSS-2) [2]. Therefore, COVID-19 appears to affect cells and tissues that co-express ACE-2 and TMPRSS-2 [3]. Interestingly, both the ACE-2 receptor and TMPRSS-2 genes are expressed on endothelial cells and likely explains why COVID-19 infection produces widespread endothelial dysfunction. Electron microscopy has demonstrated the presence of COVID-19 viral elements in endothelial cells of affected organs, such as the lung, heart, and kidney. These findings raise the question as to whether erectile tissue in the penis, rich in endothelial-lined blood vessels, can also be subject to widespread endothelial dysfunction caused by COVID-19. Here we describe the histopathological features of the penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED).
DISCUSSION
In this report, we provide evidence of COVID-19 in the human penis long after the initial infection. Our study also suggests that endothelial dysfunction from COVID-19 infection can contribute to resultant ED. Vascular integrity is necessary for erectile function, and endothelial damage associated with COVID-19 is likely to affect the penile vascular flow, resulting in impaired erectile function. We could not detect viral protein in penis tissue by immunohistology, possibly due to comparably low viral RNA load in the penis. This result was not surprising since recent studies show that COVID-19 isolation is unlikely from samples with low RNA loads [4]. H&E staining from our specimens did not show significant results compared to previous studies in which COVID-19 infection caused mild to moderate accumulation of lymphomonocytic inflammatory cells in a perivascular or subendothelial distribution [5]. Based on the current findings we can draw two hypotheses about how the SARS-CoV-2 virus can lead to the ED. First, similar to other complications related to COVID-19, ED can be the result of systemic infection resulting in widespread endothelial dysfunction. This is supported by our findings of endothelial dysfunction seen in men with COVID and ED. Second, we can also hypothesize that the worsening of these patient’s ED can be due to the virus’ presence within the cavernosal endothelium itself. This is best supported by our findings with TEM. The primary limitation of this study was the sample size (n=2) and lack of objective quantification of erectile function before and after infection for patients and controls. For now, the history of COVID-19 should be included in the work-up of ED and positive findings should be investigated accordingly. Patients should be aware of the potential complication of post-COVID-19 ED. Any changes observed in erectile function after infection should be followed up with the appropriate specialist for treatment and to help further investigation into the condition. Future studies are needed to validate the effects of this virus on sexual function.
CONCLUSION
This study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infection in humans. Our study also suggests that widespread endothelial cell dysfunction from COVID-19 infection can contribute to resultant erectile dysfunction. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection can lead to ED.
