By April 20, 2020, novel coronavirus pneumonia was diagnosed in 2 million 300 thousand of the world and 165915 cases died. In 2019, coronavirus pneumonia (covid-19) is a global epidemic pneumonia caused by the new coronavirus sars-cov-2. But more and more studies show that the infection of covid-19 can also damage the urogenital system. Studies have shown that 60% of patients with covid-19 have proteinuria at the time of admission, and 28% of patients will eventually progress to acute renal injury (AKI). Some studies also showed that the serum levels of luteinizing hormone and prolactin in patients with covid-19 were significantly increased, and some patients showed unexplained scrotal pain.
Recently, Nature Reviews urology online published a review article from Professor Wang Zengjun's team of Urology in the First Affiliated Hospital of Nanjing Medical University (Jiangsu People's Hospital). This article first systematically discusses the damage and mechanism of covid-19 on urogenital system, and learn to deal with these complications from the existing treatment experience, which is very important for improving the treatment plan and making rehabilitation plan. 　
Sars-cov-2 and Aki
Sars-cov-2 may cause renal damage directly. At present, some patients diagnosed as covid-19 have proteinuria when they are admitted to hospital. In the course of treatment, many patients gradually progress to increase the level of serum creatinine and urea nitrogen. The proportion of patients diagnosed as acute renal injury can be as high as 28%. At the same time, the serum creatinine level of severe patients was significantly higher than that of light patients, and the serum creatinine level of light patients with covid-19 was significantly higher than that of other patients with viral pneumonia and mycoplasma pneumonia. About 10.7% of the patients with AKI need continuous renal replacement therapy (CRRT).
The pathological results of renal puncture in patients with AKI with covid-19 showed that the acute renal tubules were degenerated and necrotic, while the glomeruli were not damaged. This is consistent with the renal pathological findings of SARS coronavirus in 2003 and mers in 2012. Therefore, the renal damage caused by coronavirus is mainly renal tubular damage.
Sars-cov-2 and chronic kidney disease
If patients with chronic kidney disease are infected with sars-cov-2, their prognosis may be poor. In patients with mers, chronic nephropathy before infection with mers-cov is an independent risk factor for survival. The novel coronavirus pneumonia diagnosis and treatment plan (trial version 7) indicates that if the elderly patients with chronic renal insufficiency (CKD) have COVID-19 infection, the prognosis is poor. Therefore, we suggest that the patients with CKD should strengthen the protection to avoid sars-cov-2 infection.
Sars-cov-2 and testicular damage
The testicular pathology of SARS patients showed orchitis, inflammatory cell infiltration and spermatogenic cell apoptosis. Sars-cov-2 may also cause testicular damage. A recent study showed that sars-cov-2 infection may cause gonadal dysfunction in men, which is mainly manifested by a significant decrease in the ratio of testosterone to luteinizing hormone (T: LH).
Potential mechanism of urogenital system damage caused by sars-cov-2
1. Direct damage of virus
Recently, researchers have isolated sars-cov-2 from the urine of patients with covid-19, so covid-19 may spread through this way. In addition, in line with SARS CoV and mers CoV, the nucleoprotein antigen of SARS cov-2 was only found in renal tubular epithelial cells. SARS CoV particles were found directly in the epithelial cells and Leydig cells of seminiferous tubules of testis of SARS patients by transmission electron microscopy, which provided evidence for the direct testicular damage caused by coronavirus. We suggest that we can use transmission electron microscopy to directly observe the ultrastructure of testicular cells in patients with covid-19.
2. The receptor of sars-cov-2, ACE2
Molecular biology studies have confirmed that the virus invades cells by binding to ACE2 and using cell serine protease TMPRSS2. ACE2 is highly expressed in renal tubular epithelial cells, testicular vas deferens epithelial cells, mature Leydig cells, adrenal gland and prostate gland in urogenital system. TMPRSS2 is highly expressed in kidney, prostate, seminal vesicle and epididymis. Because ACE2 and TMPRSS2 are distributed and highly expressed in some organs of urogenital system, these organs are more likely to be potential targets of sars-cov-2.
3. Theory of "inflammatory storm"
In order to resist the invasion of virus, the acquired immune cells will directly or indirectly target the renal parenchymal epithelial cells, resulting in renal damage and renal function damage. Although testis is immune immunity organ, it can not completely isolate the attack of inflammatory storm. After coronavirus infection, there will be infiltration of immune cells in Leydig tissue, which will secrete interferon to inhibit Leydig cells to produce steroids, and then destroy the normal synthesis of testosterone. The local or systemic inflammatory factors produced by these immune cells can also activate the autoimmunity, and then destroy the seminiferous epithelium to form autoimmune orchitis. The release of a large number of cytokines produced by virus or bacteria infection and other diseases or damages will destroy the normal spermatogenesis process and steroids synthesis, thus causing adverse effects on male fertility.
conclusion
Although the main clinical symptoms of covid-19 are respiratory system, the damage of urogenital system still needs attention. Elderly people with CKD have a higher risk of severe infection, and AKI is associated with the prognosis of patients with covid-19. Therefore, in the treatment of patients with covid-19, it is very important to monitor the renal function. At the same time, early use of CRRT to protect the renal function of severe patients and remove cytokines in vivo may be the key to improve the prognosis of patients. The blood testis barrier does not protect the testis from the virus, and the gonadal dysfunction may lead to the abnormal secretion of sex hormones. If covid-19 patients want to have children after recovery, it is recommended to go to the outpatient department of men's department for reproductive consultation.
Full text link: https://www.nature.com/articles/s41585-020-0319-7