Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013185/
Title: SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review
Citation: Creta, M., Sagnelli, C., Celentano, G., Napolitano, L., La Rocca, R., Capece, M., Califano, G., Calogero, A., Sica, A., Mangiapia, F., Ciccozzi, M., Fusco, F., Mirone, V., Sagnelli, E., & Longo, N. (2021). SARS-CoV-2 infection affects the lower urinary tract and male genital system: A systematic review. Journal of medical virology, 93(5), 3133–3142. https://doi.org/10.1002/jmv.26883
Recent evidence shows that COVID-19 can seed into the lower urinary tract due to significant ACE2 (angiotensin converting enzyme 2) expression in the urothelial cells, which enables the virus’ entry into host cells. This enzyme has also been found in human testes where it helps regulate the physiology of Leydig cells, Sertoli cell and spermatogonia. Studies also show that epithelial cells of human prostate also express ACE2 and TMPRSS2 (which also enable virus entry into host cells). Although these enzymes are not considered among the most frequently and intensely affected by the COVID virus, there is still evidence that shows that the urinary and male genital system is now regarded as risk for COVID infection and potentially responsible for some respiratory symptoms of COVID. The purpose of this systematic review was to demonstrate the currently available literature and data on the involvement of the urinary and male genital systems in COVID-19 and to offer Urology and ID specialists more information on this topic.
The study used 16 studies involving a total of 575 patients infected with COVID-19 who were evaluated with urinary and/or male genital involvement between January and June of 2020. The results of the study show that the male genital system and the lower urinary tract are in fact involved in COVID-19. The most common involvement of the lower urinary tract in the virus is the worsening of pre-existing lower UTI, with nocturia/urgency/incontinence/frequency being the most common symptoms. With that being said the pathogenesis behind this is not yet understood. Additionally, the bladder could also become infected with COVID by the hematogenous route from the urethral cells, where there is presence of ACE2 receptors. Evidence of this has been supported by detection of COVID in the urine of some infected infiducals. However, other systematic reviews have shown that the virus is only rarely detected in the urine (4.5% of patients) demonstrating its low risk in spreading from the urethral endothelium to the bladder. Recent literature on COVID-19 Associated Cystitis (CAC) shows that both men and women are at risk for developing CAC resulting in irritative voiding symptoms that are classic signs of a lower UTI, such as urinary frequency, nocturia, and dysuria.
In terms of genital involvement, scrotal discomfort or pain along with radiological evidence of inflammatory changes of the testis/epididymitis is the most frequently described male genital complaints in patients with COVID-19 infection. The pathogenesis of orchitis relies on the hematogenous spreading of COVID-19 to the testicular tissue, where ACE2 receptors are expressed in the Leydig cells, Sertoli cells, and spermatogonia. Additionally, postmortum studies of patients who died of severe acute respiratory distress syndrome from COVID showed the presence of orchitis with histological evidence of inflammatory changes/damage. The article also notes that the involvement of the male genitalia in COVID infections may impair fertility, and although mild COVID infection is not likely to affect spermatogenesis, the semen can be impaired after a “moderate” infection. However, keep in mind that the long term effects of COVID 19 on the male reproductive system are not yet known. Finally, low grade priapism was found in two patients with severe COVID-19, secondary to COVID coagulopathy and thrombotic complications associated with infection.
Overall, the article demonstrates that there is reason to believe that COVID-19 can seed its way into the male genitourinary tract and results in UTI symptoms, as well as scrotal/testicular symptoms indicative of a genital/urinary infection. This happens through the expression of ACE2 receptors along the GU tract, allowing COVID to access the GU tract. With that being said, the data in this research is very limited especially due to the lack of data/knowledge on the long term effects of COVID on the male GU system. Additionally, this research is based on very few studies on the topic that were often carried out with few patients and short follow ups. However, the article points out that following the second wave of the pandemic, we now know that the involvement of the GU system in COVID infections occurs in 3-5% of cases, specifically with worsening L-UTI symptoms and/or testicular/epididymal discomfort/pain which are the most common clinical findings, and in many of these cases the symptoms and clinical manifestations are significant.
