COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the Human Penis

Abstract

Purpose A pilot study to describe histopathological features of 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 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.

Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection

“…In particular, there are scarce data about the long-term persistent complications in the endocrine (outside of diabetes), gynecologic, obstetric, and rheumatologic systems. Some case reports on potential sexual dysfunction (eg, erectile dysfunction, anorgasmia) have been reported, but there is yet to be conclusive data on whether these conditions persist more than 4 weeks ( 184 , 185 ). Emerging data regarding POTS, myalgia encephalomyelitis/chronic fatigue syndrome, gastrointestinal complications, and others will need to be substantiated with greater follow-up of patients over time.…”

Predictive factors of erectile dysfunction in Egyptian individuals after contracting COVID‐19: A prospective case–control study

“…The findings of our study can be seen in line with the aetiopathological mechanisms relating ED, endothelial disease and COVID‐19 together (Sansone et al, 2021 ). Furthermore, a very recent study had detected COVID‐19 virus in the penis after initial infection in humans as well as widespread endothelial cell dysfunction from COVID‐19 infection (Kresch et al, 2021 ). The present study had demonstrated significant differences in serum testosterone between cases and controls.…”

Increased odds ratio for erectile dysfunction in COVID-19 patients

“…Another study reported on histopathological, immunohistochemical, and ultrastructural findings on penile tissue of COVID-19 patients. The authors have demonstrated the presence of the COVID-19 virus in the penis long after the initial infection in humans and suggest that widespread endothelial cell dysfunction from COVID-19 infection can contribute to ED [ 16 ].…”