ABSTRACT
OBJECTIVE: To describe the histopathological features of penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED). MATERIALS AND METHODS: After providing informed consent, penile tissue was collected from patients undergoing surgery for inflatable penile prosthesis due to severe ED under an IRB approved protocol. Two specimens were obtained from men with a history of COVID-19 infection and two specimens were obtained from men with no history of infection (all men tested negative immediately before surgery). Tissue from COVID-19 (+) and COVID-19 (-) specimens were imaged with transmission electron microscopy (TEM). The tissue was analyzed for viral RNA using polymerase chain reaction (PCR) and viral spike protein. Formalin-fixed paraffinembedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunohistochemical analysis for endothelial Nitric Oxide Synthase (eNOS) expression (marker of endothelial function). Endothelial progenitor cells (EPC) function was assessed ex vivo by determination of endothelial colony forming units from blood samples collected from the COVID-19 (+) and COVID (-) men with severe ED. RESULTS: TEM revealed extracellular viral particles ∼100 nm in diameter, with prominent peplomers (spikes), and electron-dense dots of the nucleocapsid inside the particles near penile vascular endothelial cells of the COVID-19 (+) patients. Notably, viral particles were not detected in tissue obtained from COVID-19 (-) men. COVID-19 RNA was detected in both the penis biopsy samples from men with a history of COVID, but not in the samples from COVID-19 (-) men. There were no significant differences in H&E staining between COVID-19 (+) and COVID-19 (-) men and viral spike protein was not detected. Immunohistochemistry showed decreased eNOS expression in the corpus cavernosum of COVID-19 (+) men compared to COVID-19 (-) men, consistent with endothelial dysfunction. COVID-19 spike protein-positive cells could not be detected by immunofluorescence despite positive COVID-19 PCR. EPC levels from the COVID-19 (+) men were 0 cell/well and 1.167 cell/well respectively compared to mean EPCs from 34 COVID-19 (-) men with severe ED (4.04 cells/well), suggesting impaired endothelial function. CONCLUSIONS: Our study is the first to demonstrate the presence of 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 leads to ED. IMPACT STATEMENT: COVID-19 can linger in the penis long after initial infection and can contribute to erectile dysfunction.
ABSTRACT
Objective: Our aim was to evaluate the semen parameters of men with COVID-19 infection. Design: A prospective study was performed to evaluate the gross semen parameters in men with COVID-19 infection. Samples of saliva and semen were collected and analyzed. Materials and Methods: We included men age 18-70 years old who tested positive for COVID-19. Subjects were contacted about willingness to participate. Packages with sterile specimen containers were mailed to the subject’s house with a preaddressed package included to return to our lab. The semen then underwent gross semen analysis for volume, concentration, pH and motility. Results: A total of 12 men were enrolled in the study with a median age of 35.5 (IQR = 19.5) (Table 1). The median duration of infection was 37 days (IQR = 21) and 2/12 (16.7%) had associated orchitis symptoms during the infective period. For the 11/12 men who returned a semen specimen, median volume was 1.6cc (IQR = 1.65), median pH was 7.2 (IQR = 0.2), median concentration was 14 million/cc (IQR = 30.25), and median motility of 0% (IQR = 12.5). Conclusions: We evaluated 11 men’s gross semen parameters after confirmed infection with COVID-19. The median concentration for these men is abnormally low compared to World Health Organization guidelines, and further evaluation is needed to determine the impact that COVID-19 infection can have on the testis and for what duration. [Formula presented]
ABSTRACT
Objective: The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 quickly grew into a global pandemic. The virus has been known to impact the respiratory system;however, the extent of impact on testicular tissue remains unknown. It has been found that COVID-19 binds to angiotensin converting enzyme (ACE) 2 receptors, and since ACE2 expression is high in the testes we believe COVID-19 may be prevalent in testes tissue. Design: In the present study, we analyzed the pathological changes within the testes of three patients who died of COVID-19 pneumonia and sepsis. Materials and Methods: In the present study, autopsy collection was done according to the University of Miami protocol. Testes tissue we collected from COVID-19 positive men (n=3) as well as COVID-19 negative men (n=3) to be used as controls. Tissue was formalin fixed and paraffin embedded. Samples were sectioned to 5-micron sections and stained with hematoxylin and eosin (H&E) as well as subjected to various fluorescently labeled antibodies to specifically differentiate cells or fluorescently labeled COVID RNA hybridization strands within the testes tissue. Fluorescent-labeled tissue slides were imaged on a quantitative pathology scope with various zoom levels allowing for comprehensive qualitative and quantitative imaging. Results: Among pathological examination of H&E stained slides from COVID-19 positive men, one case demonstrated increased inflammation and leukocyte infiltration, as well as occasional seminiferous tubules comprised of only Sertoli cells. The other 2 showed no abnormal change. These 2 cases had no leukocyte or macrophage infiltration, no inflammation, no abnormal basement membrane thickening, or changes to spermatogenesis. There was little to no difference between the two COVID-19 positive cases and COVID-19 negative controls. Sectioned slides from both COVID-19 positive as well as COVID-19 negative men are currently undergoing fluorescent labeled antibody staining for COVID RNA with results pending. Conclusions: This study suggests that, despite the increase in ACE2 receptor presence in testes tissue and the SARS-CoV-2 virus’ propensity to bind to said receptor, the male reproductive tract may not be targets of COVID-19 infection in all men. Whether COVID-19 RNA is detected in testes tissue remains to be evaluated.