How does SARS-CoV-2 affect the male genitourinary system?

In a recent paper published in American Journal of Clinical and Experimental Urologyinvestigators reviewed existing data on the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the male genitourinary (GU) tract.

SARS-CoV-2 entry into the host by the respiratory route is well established, and studies are being conducted to explore other potential routes of SARS-CoV-2 entry, such as semen. However, reports of transmission via the genital route are conflicting, and the long-term consequences in the male gastrointestinal tract require further investigation.

review: Effects of SARS-CoV-2 on the male genitourinary systemImage Credit: Kateryna Kon / Shutterstock

About reviews

In the current review, researchers provided a coherent summary of existing literature findings on the effects of SARS-CoV-2 infection on the gastrointestinal tract in men.

SARS-CoV-2 detection in bladder and urine

The SARS-CoV-2 spike (S) protein binds to the host angiotensin-converting enzyme 2 (hACE2) receptor for entry into host cells, and ACE2 expression has been documented by prostate and bladder urothelial cells. In addition, prostate gland cells, hillock cells, and club cells show transmembrane serine protease 2. (TMPRSS2) activity.

SARS-CoV-2-related changes in prostate TMPRSS2 levels correlate with the severity of coronavirus disease 2019 (COVID-19) and urinary tract symptoms such as urinary storage symptoms, which have been shown to be prognostic of COVID-19 ( LUTS). , although the reports are contradictory. The severity of COVID-19 has been reported to be higher in prostate cancer patients compared to bladder and kidney cancer patients.

Studies have shown that SARS-CoV-2 is taken up throughout the male genital tract of rhesus monkeys within weeks of infection by high viral loads in the testes, prostate, Pampini-like plexus, and penis, and that infectivity increases with progression of the male reproductive tract. has been reported to be correlated with

SARS-CoV-2 ribonucleic acid (RNA) has been detected in the urine of moderate or severe COVID-19 patients, but the duration of SARS-CoV-2 excretion in urine is unknown. The mechanisms underlying the effects of SARS-CoV-2 infection on the urinary tract are also unknown, but two theories have been postulated.

SARS-CoV-2 can directly enter the luminal cells of the urothelium via the ACE2 receptor pathway and cause LUTS symptoms. However, the site of ACE2 expression (bladder urothelial luminal cells or basal cells) has not been well characterized, although studies have shown higher ACE2 expression by bladder luminal cells. The exact mechanism of COVID-19-associated cystitis (CAC) with luminal urinary or basal hematogenous invasion needs to be investigated. SARS-CoV-2 RNA was rarely detected in the urine of her COVID-19 patient who recently developed urinary tract symptoms, suggesting that SARS-CoV-2 enters the bladder via the basal layer cells of the urothelium. It shows that it is propagating.

CAC can also be caused by elevated levels of COVID-19 pro-inflammatory cytokines released in the urine. For example, elevated levels of cytokines such as interferon gamma-inducible protein 10 (IP-10), chemokine ligand 1 (CXCL-1), C-reactive protein (CRP), interleukin-6 (IL-6), urinary symptoms (urinary among SARS-CoV-2-positive individuals with incontinence, urgency, frequent urination, gross hematuria or nocturia). Furthermore, the risk of symptomatic gross hematuria has been positively correlated with the severity of COVID-19.

SARS-CoV-2 detection in testis and penis

The high affinity of SARS-CoV-2 for the TMPRSS2 receptor has led to the speculation of testicular tissue invasion by SARS-CoV-2. Autopsy reports show dramatic damage to testicular architecture, with increased germ and apoptotic cells in seminiferous tubules and macrophages, and T-lymphocyte infiltration in interstitial tissue.

Electron micrographs of testicular tissue show the presence of SARS-CoV-2 in biopsy samples from survivors and deceased individuals. Moreover, increased her ACE2 expression in the testis is associated with altered sperm parameters (such as decreased sperm count) and impaired spermatogenesis. In addition, increased scrotal/testicular pain and epididymal orchitis (inflammation of the epididymis and/or testicles) have been reported among hospitalized COVID-19 patients, although there are also conflicting reports. .

Results of immunohistochemistry (IHC) analysis showed the presence of SARS-CoV-2 S in the epididymis, endothelial cells of the seminal vesicles, and capillaries, macrophages, and lymphocytes proximal to the seminal vesicles, Demonstrates penetration of the blood-testis barrier by SARS. CoV-2. In addition, SARS-CoV-2-infected inflammatory cells migrate to the testis and are subsequently taken up by spermatogonia and local macrophages, after which SARS-CoV-2 is released in complexes formed by the Golgi apparatus and endoplasmic reticulum. Duplication can occur. Therefore, SARS-CoV-2 could be detected during her recovery from COVID-19.

SARS-CoV-2 was detected in penile endothelial cells with erectile dysfunction (ED) 7 months after COVID-19 by electron microscopy. However, histopathological examination showed no disturbances in the penile structure. SARS-CoV-2 infection may be associated with long-term ED resolution after COVID-19 due to low levels of endothelial nitric oxide synthase in COVID-19.

In addition, after recovery from SARS-CoV-2 infection, patients developed penile macules, Peyronie’s disease, Mondor’s disease, and penile necrosis, possibly related to the hypercoagulable state of COVID-19. However, further research is needed to determine whether the aforementioned disease is a secondary or indirect consequence of the vascular pathophysiology of COVID-19 or a direct effect of SARS-CoV-2 entry into penile tissue. is required.

Overall, the results of the review show that SARS-CoV-2 can affect the gastrointestinal tract of men expressing ACE2 and TMPRSS2, proteins required for SARS-CoV-2 entry into the host. showed. LUTS symptoms have diagnostic and prognostic value for his COVID-19, and in addition to urinary symptoms, in COVID-19 patients he may experience sexual symptoms such as ED. However, further studies are needed to elucidate the direct and indirect mechanisms of SARS-CoV-2 lifetime, viral shedding, and COVID-19 pathogenesis in the male reproductive system.