Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

Inverse correlation between central hypogonadism and circulating IL-10 levels in males with severe COVID-19

Introduction & Objectives: After the early and dramatic induction of inflammatory cytokines, IL-6 emerged to be associated with severe outcomes in patients with COVID-19. Likewise, high IL-10 plasma levels have been reported, and central hypogonadism has been recently observed in male patients with severe clinical outcomes (i.e., Intensive Care Unit (ICU) admission or death) of COVID-19. We aimed to investigate the role of IL-10 over the pathophysiology of COVID-19 and its relationship with hypogonadism in males. Materials & Methods: Plasma from 281 voluntary healthy males (HC) and 258 laboratory-confirmed COVID-19 males (i.e., asymptomatic (n=24);symptomatic (n=155);ICU patients (n=48);and, deceased (n=31)) was collected to measure levels of total testosterone (TT), IL-10 and the nonclassical MHC class I HLA-G (HLA-G) molecule - associated to IL-10 and involved in immune escape after viral infection - by specific enzyme-linked immunosorbent assay. Results: An inverse correlation between TT and IL-10 levels was identified, with TT levels progressively decreasing from HC (median (IQR) 10.4 (8.1-13.4) nmol/L) to asymptomatic COVID-19 (3.9 (3.1-5.3) nmol/L), to symptomatic COVID-19 (3.0 (1.8-5.7) nmol/L), ICU (1.0 (0.5-1.8) nml/L) and deceased (0.7 (0.3-2.3) nmol/L) patients, respectively (p<0.0001). Conversely, IL-10 levels progressively decreased from deceased COVID-19 patients (11.3 (4.5-37.7) pg/ml), to ICU (8.0 (2.6-16.7) pg/mL), symptomatic (6.0 (3.0-10.9) pg/mL), asymptomatic COVID-19 patients (6.0 (1.6-6.0) pg/mL), and HC (3.0 (1.3-3.0) pg/mL), respectively (p<0.0001). Similarly, HLA-G levels, progressively increased from HC to COVID-19 patients with most severe clinical outcomes. Conclusions: These data indicate that circulating TT is inversely associated to both IL-10 and HLA-G levels in men with COVID-19, where lower TT and higher IL-10 levels are associated with the most severe clinical outcomes. Further investigations are required to better define whether TT and IL-10 might be early effective biomarkers of clinical severity in males with COVID-19 and to exploit if TT is involved in promoting IL-10 and HLA-G induction.

Severely low testosterone in men with COVID-19: A case-control study

Introduction & Objectives: In patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) reasons for sex disparity in disease severity are still unclear and circulating androgens could play a role. We investigated circulating sex steroids levels in a cohort of symptomatic patients with COVID-19 compared to a cohort of healthy men. Materials & Methods: Data of 286 patients with COVID-19 admitted to a single academic centre were compared to 305 voluntaryhealthy blood donors. Patients were further categorized according to disease severity as: Group 1: mildly symptomatic and discharge home;Group 2: admitted in the internal medicine unit;Group 3: admitted to intensive care unit (ICU);and, Group 4: deceased because of COVID-19. Healthy controls were subdivided in SARS-CoV-2 negative and asymptomatic unaware SARS-CoV-2 positive. Health-related comorbidities were scored with the Charlson Comorbidity Index (CCI). Moreover, a validated composite risk score (Liang et al, 2020) was calculated to estimate the risk of developing critical illness in men with COVID-19. Hypogonadism was defined as a total testosterone (TT) level < 9.2 nmol/l. Logistic regression analysis tested the association between TT level and the risk of death due to COVID-19. Results: Overall, men with COVID-19 showed a higher burden of comorbidities than healthy controls and asymptomatic positive controls (CCI³2 in 66/286 (24%) vs. 0/281 (0%) vs. 0/24 (0%);p<0.0001). TT levels were significantly lower in patients with COVID-19 vs. asymptomatic vs. healthy controls (mean (IQR) 2.5 (1-4.7) nmol/L) vs. 11.8 (8.4-14.4) vs. 10.4 (8.1-13.4) nmol/L, respectively;p<0.0001). Of all, hypogonadism was observed in 257 (89.8%) patients, 9 (33%) asymptomatic and 42 (14.9%) healthy controls at hospital admission (p<0.0001). In as many as 243 (85%) patients, hypogonadism was secondary. Of patients, in Group 1 were 24 (4.5%), in Group 2: 155 (29%), in Group 3: 48 (8.9%), and in Group 4: 31 (5.8%). Both Group 3 and 4 patients had significantly lower TT (1.0 (0.5,1.8) and 0.7 (0.3,2.3) nmol/L, respectively) compared to Group 2 (3.0 (1.8,5.7)) and Group 1 (3.9 (3.1,5.3) nmol/L) patients (p<0.0001). At logistic regression, a lower TT level was associated with a higher risk of death (OR: 0.66;95%CI 0.45, 0.98) after accounting for the critical illness score. Of note, the lower the TT, the higher the risk of death for the same Critical-Ill COVID-19 score (Figure 1).(Figure Presented) Conclusions: We unveiled an independent association between SARS-CoV-2 infection status and hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.

The effect of historical CMV infection on sperm parameters in white-European infertile men: Findings from a real-life cross-sectional study

Introduction & Objectives: In the era of SARS-CoV-2 pandemic infection, a special attention has been dedicated to largely observed viral infections. Of those, cytomegalovirus (CMV) is a higlhy prevalent infection in humans. The role of CMV infection in terms of male fertility outcomeshas been poorly investigated and it is still debated. We aimed to investigate the association between CMV infection and sperm parameters in acohort of infertile white-European men.Materials & Methods: Complete demographic and laboratory data from 1679 infertile men were analysed. Socio-demographic data, serumhormones levels and CMV serology (IgM and IgG) were investigated in all participants. Semen analyses were based on the 2010 WHO referencecriteria. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Descriptive statistics were used to test theassociation between CMV infection and sperm parameters. Logistic regression analyses tested CMV infection as a potential predictor for abnormalsperm parameters.Results: Median (IQR) age was 37 (33-41) years and median BMI was 25.2 (23.4-27) kg/m2. Of 1679 infertile men, 149 (8.1%) had CCI≥1,488 (29.1%) were smokers. Median semen volume was 3 (2-4) ml, sperm concentration 11 (2.2-34.1) x106/ml, sperm progressive motility 24%(9-38%) and normal sperm morphology 3% (1-11%). Of 1679, 57 (3.4%) and 703 (41.9%) were positive to CMV IgM and IgG, respectively. Therewere no differences in clinical and sperm parameters between men with serological tests suggestive for either current or historical CMV infectioncompared with CMV negative men (Fig. 1). Adjusted and unadjusted logistic regression analyses revealed that both CMV IgG and IgM status wasnot significantly associated with altered sperm parameters.Conclusions: Findings from this cross-sectional real-life study showed that 4 out of 10 men presenting for couples’ infertility have had CMVinfection. Current or previous CMV infections were not associated with an increased risk of abnormal sperm parameters in infertile men. Aprospective case-control study is needed to further confirm these observations.(Figure Presented)(Figure Presented)(Figure Presented)(Figure Presented)