SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected SARS-CoV-2 nucleocapsid in testicular Leydig cells of SARS-CoV-2-infected hamsters, providing evidence that Leydig cells can be infected with SARS-CoV-2. We then employed human Leydig-like cells (hLLCs) to show that the SARS-CoV-2 receptor angiotensin-converting enzyme 2 is highly expressed in hLLCs. Using a cell binding assay and a SARS-CoV-2 spike-pseudotyped viral vector (SARS-CoV-2 spike pseudovector), we showed that SARS-CoV-2 could enter hLLCs and increase testosterone production by hLLCs. We further combined the SARS-CoV-2 spike pseudovector system with pseudovector-based inhibition assays to show that SARS-CoV-2 enters hLLCs through pathways distinct from those of monkey kidney Vero E6 cells, a typical model used to study SARS-CoV-2 entry mechanisms. We finally revealed that neuropilin-1 and cathepsin B/L are expressed in hLLCs and human testes, raising the possibility that SARS-CoV-2 may enter hLLCs through these receptors or proteases. In conclusion, our study shows that SARS-CoV-2 can enter hLLCs through a distinct pathway and alter testosterone production.

Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19.

Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary-gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.

Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.

Morbidity and mortality in men: Role of androgens.

In this narrative review we provide an overview of the current literature on male hypogonadism and related comorbidities, also depicting the role of testosterone therapy (TTh) in the various settings. Male hypogonadism has been associated with major comorbidities such as type 2 diabetes mellitus, obesity and cardiovascular diseases, promoting a vicious cycle that may lead to further hypogonadism. The biological underpinnings of this association are currently under investigations, but clearly emerges the relevance of the hypothalamic-pituitary-gonadal axis. Hypogonadism has also been associated with increased risk of mortality. As such, TTh has the potential to oppose these patterns and improve cardiovascular and metabolic health in hypogonadal men. Clinical and observational data suggest that in males with hypogonadism, TTh, together with lifestyle changes and diabetes medications, may improve glycemia, reduce risk of progression to diabetes and provides positive effects on cardiovascular risk. Conversely, available data does not fully support any increased risk of prostate cancer in men under TTh. Of clinical relevance, a possible harmful role of hypogonadal status in men with COVID-19 eventually emerged.

Urological complications of COVID-19: a systematic review.

PURPOSE: COVID-19 continues to be an urgent World issue. Receptors of angiotensin converting enzyme 2 (ACE2), gateway of SARS-CoV-2, are present in the lungs, bladder, prostate, and testicles. Therefore, these organs face high risk of damage caused by the virus and this mechanism may explain non-respiratory symptoms of the disease. MATERIALS AND METHODS: This systematic review, guided by the PRIMSA statement, was proposed to elucidate possible urological complications of COVID-19. Searches were carried out in Medline (PubMed), Cochrane (CENTRAL), Embase, MedRxiv and LILACS. Bias analysis was made using the specific Newcastle-Ottawa Scale for each study design. RESULTS: Search was carried out until April 2022, and 8,477 articles were identified. Forty-nine of them were included in this systematic review. There is evidence that lower urinary tract symptoms and acute scrotum may be signs of COVID-19 in men, although in a small proportion. Also, the disease may have a transitory impact on male fertility, evidenced by several alterations in sperm counts. However, it must be clarified whether this impact is transitory, or may last for longer periods. Several patients showed reduction of total value of testosterone. Two authors linked low levels of testosterone with worse outcomes of COVID-19, suggesting that the hormone may be used as an early biomarker of the severity of the disease. Moreover, it is extremely unlikely that SARS-CoV-2 is transmitted by semen. CONCLUSION: This systematic review identified possible repercussions of COVID-19 in the urinary as well as in the male reproductive system.

How Estrogen, Testosterone, and Sex Differences Influence Serum Immunoglobulin Isotype Patterns in Mice and Humans.

Females often exhibit superior immune responses compared to males toward vaccines and pathogens such as influenza viruses and SARS-CoV-2. To help explain these differences, we first studied serum immunoglobulin isotype patterns in C57BL/6 male and female mice. We focused on IgG2b, an isotype that lends to virus control and that has been previously shown to be elevated in murine females compared to males. Improvements in IgG2b serum levels, and/or IgG2b ratios with other non-IgM isotypes, were observed when: (i) wildtype (WT) female mice were compared to estrogen receptor knockout mice (IgG2b, IgG2b/IgG3, IgG2b/IgG1, and IgG2b/IgA were all higher in WT mice), (ii) unmanipulated female mice were compared to ovariectomized mice (IgG2b/IgA was higher in unmanipulated animals), (iii) female mice were supplemented with estrogen in the context of an inflammatory insult (IgG2b and IgG2b/IgG3 were improved by estrogen supplementation), and (iv) male mice were supplemented with testosterone, a hormone that can convert to estrogen in vivo (IgG2b, IgG2b/IgG3, IgG2b/IgG1, and IgG2b/IgA were all improved by supplementation). We next examined data from three sets of previously described male and female human blood samples. In each case, there were higher IgG2 levels, and/or ratios of IgG2 with non-IgM isotypes, in human females compared to males. The effects of sex and sex hormones in the mouse and human studies were subtle, but frequent, suggesting that sex hormones represent only a fraction of the factors that influence isotype patterns. Examination of the gene loci suggested that upregulation of murine IgG2b or human IgG2 could be mediated by estrogen receptor binding to estrogen response elements and cytosine-adenine (CA) repeats upstream of respective Cγ genes. Given that murine IgG2b and human IgG2 lend to virus control, the isotype biases in females may be sufficient to improve outcomes following vaccination or infection. Future attention to sex hormone levels, and consequent immunoglobulin isotype patterns, in clinical trials are encouraged to support the optimization of vaccine and drug products for male and female hosts.

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

[Androgenic status in men during COVID-19].

BACKGROUND: COVID-19 is a disease that has a negative systemic effect on the human body, including the male gonads. Therefore, the androgenic status in men with COVID-19 needs to be studied. AIM: To evaluate the levels of total testosterone, sex hormone binding globulin (SHBG) and free testosterone in men in the acute phase of COVID-19 and during convalescence. MATERIALS AND METHODS: A continuous dynamic prospective study of 70 men with moderate to severe COVID-19 at the age of 50[44; 64] years. During the study, the levels of total testosterone, SHBG were determined with further calculation of the level of free testosterone by Vermeullen. The data were collected twice - at the patient's hospitalization and at his discharge. The differences between the groups were considered statistically significant at p <0.05. RESULTS: At the time of hospitalization for COVID-19, hypogonadism syndrome was observed in 61 people - 87%. Patients with hypogonadism did not statistically significant differ in age and severity of COVID-19 disease compared to men without hypogonadism. Inpatient treatment lasting 12[10;14] days resulted in a statistically significant increase in the levels of total testosterone from 4,7[2,96;8,48] to 12,85[8,62;19,2] nmol/l, p<0,001; SHBG from 27,87[20,78;36,57] to 33,76[26,27;52,60] nmol/l, p<0,001 and free testosterone from 107[65;174] to 235[162;337] pmol/l, p<0,001. This led to the elimination of hypogonadism in 28 patients - 40%. Patients with persistent hypogonadism were statistically significantly older than men with normalized testosterone, there were no statistically significant differences in the initial levels of total testosterone, SHBG and free testosterone, and there were also no differences in the prevalence of severe COVID-19 (3,97[2,86;7,46] vs 4,26[2,93;5,96] nmol/l, p=0,100; 28,76[20,78;48,59] vs 24,63[18,85;31,70] nmol/l, р=0,994; 100[58;118] vs 96[64;143] pmol/l, p=0,522; 24 против 18%, p=0,754, respectively). CONCLUSION: COVID-19 has a pronounced negative effect on the production of testosterone in men, leading to the development of laboratoric hypogonadism, which is potentially reversible. The reversibility of laboratoric hypogonadism is typical for younger patients.

Can We Identify Patients in Danger of Delayed Treatment? Management of COVID-19 Pandemic Backlog in Urology Care in Poland.

The COVID-19 pandemic had a tremendous impact on healthcare systems around the world. This study aims to research the course of surgical treatment in urology during the pandemic in 2020, evaluate the volume of deferred treatment in urology in Poland, and indicate groups of patients that are especially vulnerable to a delay in the delivery of healthcare services. The National Health Found statistics (NHF) database was searched for information on procedures completed in urology departments from 2015 to 2020. Changes in hospital discharges of adults from 2019 to 2021 were investigated using monthly reports of NHF on patient billing groups. Statistics of PSA, testosterone, and creatinine testing were extracted from NHF reports. Annual changes in the number of surgeries were calculated. Then, the estimation of the expected quantity of procedures without the occurrence of the pandemic was performed using linear regression based on data from 2015 to 2020. The estimation was assumed reliable at R2 > 0.8. The difference between collected and estimated data was analysed. In 2020, the volume of radical prostatectomies, cystectomies, and kidney surgeries noted downturns following lockdowns in March and November. All analysed procedures, except radical cystectomy, noted a reduction in the entire year. The declines reached -34% in shockwave lithotripsy, -13% in ureterorenoscopic lithotripsy, -22% in cystolithotripsy, -28% in percutaneous lithotripsy, -12% in transurethral resection of a bladder tumour (TURBT), -31% in transurethral resection of the prostate, -15% in nephrectomy and kidney tumorectomy, and -10% in radical prostatectomy. Among the analysed procedures, only radical cystectomy rates increased 5%. Prostate-specific antigen and creatinine tests fell -17%, and testosterone testing was down -18%. In conclusion, the patients most vulnerable to delayed treatment due to the post-pandemic backlog are those requiring TURBT, kidney cancer operations, and radical prostatectomies. Solving backlogs in urology should prioritise cancer patients and thus requires improved access to cystoscopy, TURBT, diagnoses and surgery of prostate and kidney tumours. Addressing the needs of patients suffering from benign diseases demands appropriate measures to increase the surgical productivity of urology departments.

Genetically predicted high IGF-1 levels showed protective effects on COVID-19 susceptibility and hospitalization: a Mendelian randomisation study with data from 60 studies across 25 countries.

Background: Epidemiological studies observed gender differences in COVID-19 outcomes, however, whether sex hormone plays a causal in COVID-19 risk remains unclear. This study aimed to examine associations of sex hormone, sex hormones-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and COVID-19 risk. Methods: Two-sample Mendelian randomization (TSMR) study was performed to explore the causal associations between testosterone, estrogen, SHBG, IGF-1, and the risk of COVID-19 (susceptibility, hospitalization, and severity) using genome-wide association study (GWAS) summary level data from the COVID-19 Host Genetics Initiative (N=1,348,701). Random-effects inverse variance weighted (IVW) MR approach was used as the primary MR method and the weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test were conducted as sensitivity analyses. Results: Higher genetically predicted IGF-1 levels have nominally significant association with reduced risk of COVID-19 susceptibility and hospitalization. For one standard deviation increase in genetically predicted IGF-1 levels, the odds ratio was 0.77 (95% confidence interval [CI], 0.61-0.97, p=0.027) for COVID-19 susceptibility, 0.62 (95% CI: 0.25-0.51, p=0.018) for COVID-19 hospitalization, and 0.85 (95% CI: 0.52-1.38, p=0.513) for COVID-19 severity. There was no evidence that testosterone, estrogen, and SHBG are associated with the risk of COVID-19 susceptibility, hospitalization, and severity in either overall or sex-stratified TSMR analysis. Conclusions: Our study indicated that genetically predicted high IGF-1 levels were associated with decrease the risk of COVID-19 susceptibility and hospitalization, but these associations did not survive the Bonferroni correction of multiple testing. Further studies are needed to validate the findings and explore whether IGF-1 could be a potential intervention target to reduce COVID-19 risk. Funding: We acknowledge support from NSFC (LR22H260001), CRUK (C31250/A22804), SHLF (Hjärt-Lungfonden, 20210351), VR (Vetenskapsrådet, 2019-00977), and SCI (Cancerfonden).

Do the Covid-19 vaccines affect the reproductive parameters of men?-A Northern Saudi experience.

Background: The COVID-19 vaccine acceptance is a psychological behavior influenced by many factors, including fear of an adverse effect on the reproductive system. Aims: The aim of this study is to assess the COVID-19 vaccines effect on reproductive parameters among the male population of northern Saudi Arabia. Patients and Methods: We conducted a prospective cohort study among 100 volunteers who received two doses of COVID-19 vaccines. A pre- and post-vaccination blood sample was collected and analyzed for testosterone, prolactin, and follicle-stimulating hormone (FSH). Semen samples were also collected and analyzed. The Wilcoxon signed-rank test was used to compare the values between pre- and post-vaccination. Results: Of the 100 samples analyzed, there was a significant increase in progressive sperm motility after the second dose of vaccination, but the increase was within the physiological limits (pre-55.03 [42.00-61.75] vs. post-57.50 [42.25-63.00], P = 0.008). Similarly, a significant increase in serum testosterone level after the second vaccination dose was observed (pre-380.65 [301.60-485.73] vs. post-410 [318.18-505.35], P = 0.016). Conclusion: These preliminary results show that the COVID-19 vaccines do not have any adverse effect on the reproductive parameters of men. A prospective long-term follow-up study will be necessary on all WHO -approved COVID vaccines to determine their long-term effect on men's reproductive health. The future follow-up study could strengthen our findings and encourage the men who have vaccine hesitancy to take due to fear of its effect on reproductive parameters.

Coexistence of growth hormone, adrenocorticotropic hormone, and testosterone deficiency associated with coronavirus disease 2019: a case followed up for 15 months.

Coronavirus disease 2019 (COVID-19) is associated with endocrine disorders, but their long-term clinical course remains unclear. We here report the 15-month clinical course for an individual with multiple endocrine disorders of the pituitary gland and testis likely triggered by COVID-19. A 65-year-old man with no history of endocrinopathy was admitted for acute COVID-19 pneumonia. Although his respiratory condition improved after administration of antiviral drugs, his blood pressure dropped suddenly to a preshock level and was refractory to vasopressors. The circulating adrenocorticotropic hormone (ACTH) and cortisol concentrations were low, and secondary adrenal insufficiency was suspected. Administration of hydrocortisone rapidly ameliorated the hypotension, and the patient was discharged taking 15 mg of hydrocortisone daily. An insulin tolerance test performed 3 months later revealed impaired ACTH, cortisol, and growth hormone (GH) responses, indicative of combined hypopituitarism. The patient also manifested symptoms of hypogonadism, and a hormonal workup suggested primary hypogonadism. At 12 months after discharge, GH and ACTH responses had recovered completely and partially, respectively. After another 3 months, basal ACTH and cortisol levels had been restored to the normal range and the patient discontinued hydrocortisone replacement without exacerbation of symptoms, although his hypogonadism persisted. The patient thus developed transient GH and ACTH deficiency that lasted for more than a year as well as persistent primary hypogonadism during intensive care for COVID-19. Certain prolonged symptoms of COVID-19 might be accounted for by such hormonal disturbance.

GONADOTROPIN AND SEX STEROID HORMONES IN MALES WITH POST COVID-19 INFECTION.

OBJECTIVE: The aim: To understand the effects of COVID-19 infection on gonadotropins and sex steroid hormones in males. PATIENTS AND METHODS: Materials and methods: This is a cohort study conducted in fifty males, who had been previously infected with COVID-19 with normal hormonal profile. Fifty Iraqi males were attending the male clinic at Higher Institute of Infertility Diagnosis and Assisted Reproductive Technologies, diagnosed with standard methods. The assessment of serum hormonal levels including (FSH, LH, Prolactin and Testosterone) was done 3 times: 1st time after one-month post recovery after COVID-19, 2nd time after 2 months post recovery and 3rd time - after 3 months post recovery. RESULTS: Results: There was no significant change in the mean level of serum FSH during the first, second and third months (p = 0.630). LH serum level was highly significantly reduced during follow up (p< 0.001). Serum prolactin level, reduced significantly during follow up (p< 0.001). Serum testosterone level was the lowest in the first month and increased during the second month and then during the third month in a highly significant manner (p< 0.001). CONCLUSION: Conclusions: Sub-clinical hypogonadism may be suspected as a consequence of COVID-19 infection in males as its first presentation characterized by increased LH & decreased testosterone production.

Associations between COVID-19 infection and sex steroid hormones.

Aims: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and within a few months of the first outbreak, it was declared a global pandemic by the WHO. The lethal virus SARS-CoV-2 is transmitted through respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors are highly expressed in many tissues, including testes. Therefore, the objective of this study was to summarize the available literature regarding the correlation between sex hormone levels and COVID-19. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were reviewed systematically through August 2022 for studies comparing sex hormone levels between different patient groups: COVID-19 versus no COVID-19, more severe versus less severe COVID-19, and non-survivors versus survivors. Various types of clinical research reporting sex hormone levels, including free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17ß-oestradiol (E2), the oestradiol-to-testosterone ratio (E2/T), prolactin (PRL), and sex hormone-binding globulin (SHBG), were included. Random- or fixed-effects models were used to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity among the studies was assessed by the I2 index, and data analyses were performed using meta-analysis with Stata version 12.0. Results: Twenty-two articles that included 3369 patients were ultimately included in the meta-analysis. According to analysis of the included studies, patients with COVID-19 had significantly low T/LH, FSH/LH, and SHBG levels and high levels of LH, and E2/T, but their levels of FT, FSH, PRL, E2, and progesterone were not affected. Publication bias was not found according to funnel plots and Egger's regression and Begg's rank correlation tests. Conclusion: Low T/LH, FSH/LH, and SHBG serum levels and high LH, and E2/T levels may increase the risk of COVID-19. Additionally, the greater is the clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in T/LH, FSH/LH, and SHBG levels. COVID-19 may have unfavourable effects on gonadal functions, which should be taken seriously by clinicians. Routine monitoring of sex hormone levels might help clinicians to evaluate disease severity in patients with COVID-19.

Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells.

BACKGROUND: COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses. METHODS: A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17ß-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated. RESULTS: The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect. CONCLUSION: GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.

Examining changes on testicular structure and sperm analysis of COVID-19 patients.

This study aimed to examine the testicular functions with sperm analysis of patients with COVID-19. The study was carried out with male patients aged between 18 and 50 years with positive RT-PCR test and SARS-CoV-2 virus between December 2020 and April 2021. A total of 103 participants were included in the study. The mean age was 31.24 ± 5.67 (19-45) years and the mean body mass index of the participants was 28.41 ± 4.68 kg/m2 . The patients were divided into two groups, group-1 was patients who had COVID-19, group-2 was healthy men. A semen analysis of both groups was performed, and the serum total testosterone, FSH, LH, anti-mullerian hormone and Inhibin-B tests were analysed and recorded. The testicular dimensions and testicular densities were examined by ultrasound and elastography for both groups. Comparing the patient and control groups results, this study found that the sperm count per 1 cc (p = 0.01) and total motility (p = 0.01) in group-1 was lower than in the control group, the testicular dimensions decreased (for right testis group-2 was 15.39 ± 4.78 ml versus group-1 was 12.11 ± 4.62 cm3 p < 0.01, for left testis group-2 was 16.01 ± 5.12 versus group-1 was 11.92 ± 4.78 cm3 ; p < 0.01), and the shear wave velocities were significantly higher in group-1 patients. In conclusion, sperm parameters deteriorate in men who have symptomatic disease with SARS-CoV-2 infection. The fact that the cause of this deterioration is characterized by changes at the cellular level in the testis raises doubts about the persistence of this condition.

The impact of COVID-19 vaccines on fertility-A systematic review and meta-analysis.

BACKGROUND: Despite literature's evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by misinformation and anti-vaccine campaigns. The present study aims to answer the question: Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age? METHODS: PubMed, Scopus, Web of Science, Cochrane and Embase databases were searched for eligible studies until June 8th, 2022. The search was restricted to articles regarding humans, published in any languages, without additional restrictions. Studies' quality was assessed by the Newcastle-Ottawa and the Before and After Quality Assessment scales for cohort and pre-post studies, respectively. Random-effect meta-analyses were performed for parameters considered in ≥ 2 studies, calculating means, p-values and 95 % Confidence Intervals (CIs). RESULTS: Out of 1406 studies screened, 29 were included in the systematic review. These studies, conducted in Israel (34.5 %), USA (24.1 %), Russia (20.7 %) China (10.3 %), Italy (3.5 %), North America (3.5%) and Turkey (3.5 %) were of poor (34.5 %), moderate (58.6 %) and good (6.9 %) quality. Meta-analyses were performed for pre- and post-vaccination sperm progressive motility (44 %, 95 % CI 42 %-62 % vs 43 %, 95 % CI 31 %-59 % p = 0.07) and concentration (50.6 mln/ml, 95 % CI 35.1-72.8 vs 55.4 mln/ml, 95 % CI 37.4-82.2p = 0.12). Biochemical (0.51, 95 % CI 0.40-0.66 vs 0.60, 95 % CI 0.53-0.68p = 0.45) and clinical (0.45, 95 % CI 0.37-0.54 vs 0.47, 95 % CI 0.40-0.55 p = 0.31) pregnancy rate did not differ among vaccinated and not vaccinated groups. Subgroup meta-analyses based on the type of vaccine showed no significant difference: between vaccinated with mRNA vaccines and non-vaccinated regarding biochemical pregnancy rates; pre- and post-vaccination with Gam-COVID-Vac regarding testosterone, FSH and LH levels; pre- and post-vaccination with BNT162b2 vaccines regarding sperm volumes. CONCLUSION: Based on the studies published so far, there is no scientific proof of any association between COVID-19 vaccines and fertility impairment in men or women.