The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

COVID-19 disease in clinical setting: impact on gonadal function, transmission risk, and sperm quality in young males.

OBJECTIVES: We want to evaluate the possible presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in semen samples and semen quality, looking for a possible relationship between the infectious disease and fertility. METHODS: In this prospective study, we enrolled 15 consecutive men (age 18-50 years) with positive oropharyngeal swab to SARS-CoV-2 and classified, according to WHO criteria, in mild to moderate disease. A semen sample was collected to detect SARS-CoV viral RNA by the automated Real-Time PCR ELITe InGenius® system and the GeneFinderTM COVID-19 Plus RealAmp Kit assay (ELITechGroup, France). Analysis of semen characteristics was performed according to WHO laboratory manual 5th ed. for the examination and processing of human semen. Blood samples for the dosage of hormonal assay, procalcitonin, interleukin 6, C-reactive protein were obtained. RESULTS: SARS-CoV-2 RNA has not been detected in semen samples from any of the subjects analysed. Sperm analysis exhibited abnormal seminal values in 14 out of 15 patients (93.3%). Furthermore, no difference was detected regarding sperm quality between mild and moderate SARS-CoV-2 patients. No alteration in the inflammatory indices was observed in the studied population, as well gonadotropins and testosterone levels. CONCLUSIONS: COVID patients studied exhibits alteration of the seminal fluid both in microscopic and macroscopic characteristics such as hypoposia and increased viscosity, which have not been detected in previous studies. The presence of viral RNA within the seminal fluid was excluded.

The Impact of SARS-CoV-2 Pandemic on Time to Primary, Secondary Resection and Adjuvant Intravesical Therapy in Patients with High-Risk Non-Muscle Invasive Bladder Cancer: A Retrospective Multi-Institutional Cohort Analysis.

BACKGROUND: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). METHODS: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. RESULTS: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001). CONCLUSIONS: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.

Overview of the italian experience in surgical management of bladder cancer during first month of COVID-19 pandemic.

OBJECTIVE: Overview of bladder cancer (BC) management in Italy during the first month of the COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered "usual activity" period. The aim is to analyze performance of different Italian Centers in North, Center and South, with a special eye for Lombardy (the Italian epicenter). PATIENTS AND METHODS: During April 2020, a survey containing 14 multiple-choice questions focused on general staffing and surgical activity related to BC during the months of March 2019 and March 2020 was sent to 32 Italian Centers. Statistical analysis was performed using IBM SPSS Statistics (v26) software. A Medline search was performed, in order to attempt a comparative analysis with published papers. RESULTS: 28 Centers answered, for a response rate of 87.5%. Most of the urology staff in the Lombardy region were employed in COVID wards (p = 0.003), with a statistically significant reduction in the number of radical cystectomies (RC) performed during that time (p = 0.036). The total amount of RC across Italy remained the same between 2019 and 2020, however there was an increase in the number of surgeries performed in the Southern region. This was most likely due to travel restrictions limiting travel the North. The number of Trans-Urethral Resection of Bladder Tumors (TURBT) (p = 0.046) was higher in Academic Centers (AC) in 2020 (p = 0.037). CONCLUSIONS: The data of our survey, although limited, represents a snap shot of the management of BC during the first month of the COVD-19 pandemic, which posed a major challenge for cancer centers seeking to provide care during an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. METHODS: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). RESULTS: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). DISCUSSION/CONCLUSION: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.