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Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.
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Background: Fitness is a marker of physiological and mental health. The purpose of this pilot study was to assess the feasibility of processes to recruit women with polycystic ovary syndrome (PCOS) during the Covid pandemic and collect their health and fitness data. Additionally, the data was used to explore possible associations between anthropometrics, PCOS biomarkers, health-related quality-of-life (HRQoL), and depressive symptoms with that of fitness and self-reported physical activity levels among women with PCOS. Method(s): A convenience sample of women with PCOS (n = 15) were recruited via flyers and the snowball method. Participants completed surveys, anthropometrics, a dual energy x-ray absorptiometry scan, blood work, and a fitness assessment. Data were statistically analyzed using Spearman correlations. Result(s): Feasibility measures of recruitment and retention rates were 83% and 100%, respectively. Fidelity measurement for process averaged 97%. Participants (age 25.9 (+/- 6.2), mostly White (80%), single (60%), and employed full-time (67%)) were categorized as obese (body mass index (BMI) 32.2 kg/m2 +/- 8.3, percent bodyfat 41.1% +/- 8.1) with <=1 comorbidity. Most participants were not regularly physically active and had high free testosterone levels (7.6 pg/mL+/-4.3), elevated high-density lipoprotein (63.2 mg/dL+/-12.9), fair cardiovascular capacity, and below average muscular strength/endurance. The following statistically significant and strong associations were found: (1) VO2 max with percent bodyfat (-0.59;p = 0.02), sex hormone binding globulin (0.73;p = 0.00), HRQoL (0.72;p = 0.00), and depressive symptoms (-0.67;p = 0.00), (2) abdominal strength with BMI (-0.66;p = 0.01) and high density lipoprotein (HDL) (0.59;p = 0.02), (3) physical activity level with percent bodyfat (-0.72;p = 0.00), and (4) resistance training with low density lipoprotein (LDL) (-0.52;p = 0.05). Conclusion(s): Collecting health and fitness data from women with PCOS is a feasible research approach. Randomized controlled trials in which health and fitness data are collected from women with PCOS are needed to confirm possible associations between fitness and PCOS clinical features and is in the planning process. Copyright: Copyright © 2023 The Author(s).
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Case Report: A 28 year old male with a past medical history of hypothyroidism and positive ANA presented to an outpatient dermatology clinic with a diffuse pruritic rash two weeks after the administration of his first Moderna COVID booster vaccine. He denied any other accompanying symptoms such as fever or chills as well as any similar rashes to prior doses of the Moderna COVID vaccine. The rash consisted of pink erythematous minimally scaly papules, thin plaques and patches involving the left and right dorsal hands, forearms, wrists, face, neck and left shoulder. The remainder of the patient's skin including the bilateral lower extremities, the eyelids, conjunctiva and oral mucosa was clear. The patient denied any similar rashes in the past. The patient denied any allergies to medications, or food or environmental allergies. He denied any notable contact allergen exposures, including to soaps, lotions, and cosmetic products. The patient also denied any significant family history or past surgical history. The patient was on Armour Thyroid for hypothyroidism and testosterone for low levels since age eighteen. The patient was started on cetirizine 10 mg once daily for the rash with minimal improvement. Autoimmune workup for the rash was notable for an elevated anti-RNP and as the patient's past medical history included Raynaud's phenomenon and ANA positivity for ten years, the patient was diagnosed with mixed connective tissue disease (MCTD). Autoimmune conditions can often have an indolent course, where symptoms progressively develop and worsen. MCTD is an autoimmune overlap syndrome that can consist of the following three connective tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis. Millions of individuals across the world are receiving COVID vaccines to protect themselves and members of their community, and it is of utmost importance that we continue to investigate adverse events. Although of low incidence, these rare effects have the ability to impact large numbers of people within both healthy and immunocompromised populations. It is critical that we examine and document them in a rigorous manner, to ensure safe vaccine delivery and reassure the public about vaccine safety overall.
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Background: Long-acting cabotegravir (CAB-LA) is highly effective as HIV PrEP and superior to daily oral F/TDF in sexually active adults. We report a 28-yearold gender diverse patient assigned male at birth who acquired HIV-1 91 days after transitioning from F/TAF to CAB-LA despite on-time dosing. Method(s): Electronic medical records were reviewed to assess patient history and CAB-LA administration details. Plasma 4th generation HIV-1/2 Ag/Ab combination immunoassay and HIV-1 RNA quantitative PCR were performed at each injection visit. Result(s): Patient was on daily F/TAF for ten months prior to CAB-LA with acceptable adherence, missing 1 dose per week. Their medical history included hypothyroidism on levothyroxine and unconfirmed hypogonadism with illicit use of IM testosterone cypionate complicated by significantly elevated total testosterone levels. They were sexually active with cisgender men, endorsing condomless oral and anal sex with one primary partner and 20-30 unique partners per month. In the past 6 months, patient was diagnosed with syphilis and mpox. Patient was given 600mg of CAB-LA into their left gluteal medius on Day 0, 27, and 91. Day 0 and 27, plasma HIV 1/2 Ag/Ab was non-reactive and HIV-1 RNA PCR was not detected. Patient reported flu-like illness on Day 76 with positive SARS-COV-2 PCR;they completed a five-day course of nirmatrelvirritonavir with rapid resolution of symptoms. At the third injection of 600mg CAB-LA on Day 91, their plasma HIV 1/2 Ag/Ab was non-reactive but the HIV-1 RNA PCR test was detected at 1.48log c/mL. On repeat testing on Day 100, plasma HIV 1/2 Ag/Ab was reactive with HIV-1 Ab detected on differentiation assay and HIV-1 RNA PCR was detected at 1.30 log c/mL. Patient's primary partner was living with HIV resistant to NRTIs (65R, 118I) and INSTIs (92G) with undetectable plasma HIV-1 RNA for the past 24 months. Patient's viremia was below the threshold to perform standard HIV-1 sequencing;HIV-1 DNA qualitative PCR and HIV-1 proviral DNA resistance testing are currently pending. Patient ultimately started on F/TAF/DRV/COBI and DTG on Day 112. Conclusion(s): This patient's history suggests HIV-1 infection despite on-time and appropriate CAB-LA injections. To our knowledge, this is the first case of CAB-LA PrEP failure outside the setting of a clinical trial and highlights the diagnostic and management challenges that may arise with such breakthrough infections in the real world.
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The aim of our study is analysis of the androgenic status including testosterone (T) and dihydrotestosterone (DHT) in men hospitalized with coronavirus disease 2019 (COVID-19) and them relationship with the course of the disease. This is a monocentric prospective study performed on 125 male patients hospitalized for COVID-19. We conducted hematological examination, blood biochemical profile, hemostasis analysis and hormonal examination (T and DHT levels) lung and chest computed tomography and also assessed outcomes of hospitalization. Low DHT serum level was found only in 18 patients (14.4%). Subjects with low DHT were significantly older compare to subjects with normal DHT. At the same time in patients with normal DHT white blood cells (WBC) count, neutrophils at admission were higher than in patients with low DHT. No correlation was observed between T and DHT serum blood levels. C-reactive protein (CRP) has a weak positive correlation of DHT serum blood concentration (r = 0.22;p = 0.016). The inverse pattern was obtained for T serum blood concentration (r = -0.285;p = 0.001). After divided all males according to T concentrations we conducted next correlation analysis for DHT and CRP in two different groups: with normal T levels and with low T levels. We found that in males with normal T DHT levels are not correlated with CRP (r = 0.095;p = 0.462). However, in males with low T DHT and CRP had weak positive correlation with r = 0.317 (p = 0.012). Higher DHT concentrations are associated with higher CRP levels, however correlation is weak and in patients with normal T is absent, that may indicate anti-inflammatory effect of T and possible proinflammatory effect of DHT.Copyright © 2023 The Author(s).
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Objectives Severe acute respiratory syndrome coronavirus 2 has infected millions of people worldwide with extensive affection and damage to body systems and organs;hence, the study of post-coronavirus disease (COVID) sequences is mandatory. Till now, reports are upcoming on the considerable effects of COVID-19 on male sexual health with no final data. Patients and Methods: Our cohort study included 76 male COVID-19-infected patients, confirmed positive via nasopharyngeal PCR swab. The rationale of this study was to estimate the influence of clinical, laboratory, and radiological severity parameters of COVID-19 on male erectile dysfunction based on erectile scores and male sex hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol). Result(s): Our results have demonstrated a highly statistically significant correlation between COVID-19 severity (mild, moderate, and severe cases) and both erectile scores (erection hardness score and International Index of Erectile Dysfunction-5) and testosterone hormones at first and third month after COVID (P0.001), except for testosterone level at third month and COVID-19 severity, which showed a statistically significant difference, with P value of 0.031. Conclusion(s): The current study correlated the effect of COVID-19 severity in the terms of clinical, laboratory, and radiological presentations on male sexual dysfunction (erectile scores and testosterone hormone) at first and third month after hospital discharge, with statistical significance being highly affected in severe rather than moderate and mild cases. This strengthens the obvious effect of COVID-19 infection on male sexual dysfunction. Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.
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COVID-19 (coronavirus disease 2019), cause severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) across all age groups, it’s a positive-sense single-stranded RNA virus, and a member of the Betacoronavirus genus taxonomically (Jiang et al, 2020). Given the importance roles of zinc in combating oxidative damage and viral infections, Zinc also has confirmed roles in both male and female reproduction. The possible depletion of zinc with the oxidative events of COVID-19 is especially relevant to the fertility of affected couples (Sethuram et al, 2021). The aim of study is to determine the relation between zinc value and oxidative stress level represented by ROS (Reactive Oxygen Species) and testosterone level among the recovered COVID-19 patients in reproductive age. 120 men chosen from Center of Medical City, Health Center of 9 Nisan, Poisoning Consultation Center and Kamal AL-Samarrai Hospital, 70 recovered males from COVID-19 within a period of 6 months after the last negative PCR nasopharyngeal swab and 50 as control group (uninfected COVID-19) from the Medical staff and the relatives, during the period from December/ 2020 to February / 2021. Testosterone hormone level were measured for each male, level of COVID-19 anti-nucleocapsid IgG was estimated and designed as selection criteria for recovery from COVID-19. Pearson’s correlation coefficient and A stepwise method in linear regression statistic test was applied to detect the association of testosterone hormone level with zinc and ROS. The mean and standard deviation level of studied parameters are differ between cases of current studying;recovering COVID-19 males and control group then compared with normal value of each test. The levels of COVID-19 anti-nucleocapsid IgG increase among recovering males compared with control group, statistically highly-significant (P-value = 0.00), as well oxidative stress among cases recovered from Covid-19 compared with level of control are statistically highly-significant (P-value= 0.00), while levels of zinc are decreased among cases studied compared with control group, this differences was highly-significant (P-value = 0.00). In conclusion, the most factors affecting Testosterone hormone level identified in the study are Zinc, ROS
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Coronavirus disease 2019 discovered in December 2019, Wuhan, China. It was transmitted globally producing the present COVID-19 pandemic. Concerns have been raised about the potential impact of COVID-19 on male reproductive organs and male fertility as the number of infections in the male community has increased. The objectives of current study are studying the relationship between the plasma levels of testosterone and the markers of immune reaction with the severity and mortality in a sample of COVID-19 patients. A cross section study included NO= 103 male patients affected by SARS-CoV-2 pneumonia, diagnosed by PCR and chest CT scan, (≥ 18 years old), and recovered in the respiratory intensive care unit (RICU). Several biochemical risk factors were determined Free Testosterone, sex hormone binding globulin (SHBG) were measured by Enzyme-Linked Immunosorbent Assay(ELISA), D-dimer, Ferritin, CRP, Urea, Creatinine were measured by automated method by using Abbott Architect c4000 and Complete Blood Count(CBC). The results show that the serum free testosterone and SHBG levels a significant lower in non-survivor patients than survivor patients with COVID-19. While the other biomarkers (D-dimer, Ferritin, Urea, Creatinine) were significant higher in non-survivor patients than survivor patients. The CRP, WBC and lymphocyte showed that no significant between the both group of patients. In conclusion the study showed that lower free testosterone and SHBG levels enable significant role in increasing risk of COVID-19 mortality amongst adult male patients.
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Objective: Men appear at greater risk of poor clinical outcomes and death from Covid-19. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: 110 men consecutively admitted to a district general hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2. Factors associated with mortality in the latter group were analysed. Results: No significant difference was found (p=0.12, rank-sum test) in serum TT between men positive and negative for SARS-CoV-2. Serum TT was lower (p=0.0011, rank-sum test) in men with COVID-19 who died (median TT 2.0nmol/L) compared with survivors (median TT 5.0nmol/L). Mortality (logistic regression) was associated with age and serum TT (odds ratio: 0.77, 95% confidence intervals (CI): 0.64, 0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio (HR): 0.85 (95% CI: 0.74, 0.98), stratified by median, TT ≥ 3.9nmol/L (reference, TT < 3.9nmol/L), HR:0.24, (95% CI: 0.089, 0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and whilst managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to a poorer prognosis and a role for testosterone therapy.
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OBJECTIVE: Severe acute respiratory syndrome corona virus 2 (SARS-COV-2) enter different body tissues via the angiotensin-converting enzyme 2 (ACE2) receptor. This enzyme is highly expressed in testicular tissue making testicular hormone function & spermatogenesis vulnerable to such infection. This study aims to evaluate the effect of SARS COV-2 infection on the testicular function in proven fertile males on short & long term basis MATERIALS AND METHODS: This prospective cohort study enrolled patients infected with SARS COV-2 virus. Patients with normal semen analysis or evidence of fertility in the past 2 years were included. Patients with history of infertility or those receiving treatment & had abnormal semen parameters prior to infection were excluded. Patients were divided into asymptomatic & symptomatic group requiring hospitalization. Medical history & physical exam were performed during the initial visit and blood hormones were withdrawn. Patients underwent conventional semen analysis, advanced sperm function tests & hormone tests at 3 & 6 months following infection. Variables were reported as mean ± SE & compared using Kruskal Wallis Test. Spearman correlation was performed to assess relationship between Ct PCR value & numerical variables RESULTS: A total of 60 patients infected with SARS COV-2 virus were included & 48 patients completed the study. The mean age was 35.1±5.6 years. The mean Ct value was 23.38±5.2. There was no significant correlation between the Ct value, the hormonal profile & patient age at time of recruitment. The semen parameters & hormonal profile at 3 & 6 months follow up were in normal range (Table 1). There was significant difference in the testosterone levels between asymptomatic group (mean 11.35 ± 4.8) & symptomatic hospitalized group (mean 7.48 ± 3.49) upon initial enrollment (P value=0.005). Decreased testosterone levels during infection turned back to normal on 6 months follow up (mean 12.78±4.98) CONCLUSIONS: SARS COV-2 infection does not affect semen parameters nor hormonal profile for previously fertile patients on short & long term basis. Testosterone levels in symptomatic hospitalized patients is significantly decreased compared to asymptomatic non-hospitalized group at the time of SARS COV-2 infection IMPACT STATEMENT: Long term reproductive health of men is not affected by SARS COV-2 infection. (Table Presented).
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in the blood, urine, facial/anal swabs, semen, and vaginal discharge;all have been shown to contain SARSCoV-2 RNA. Recent findings have highlighted the prospect of SARS-CoV-2 invading the genital system in addition to other tissues, which might give rise to reproductive concerns. This investigation sheds light on male reproductive tract vulnerability to invasion by SARS-CoV-2 and provides a foundation for further researches into male fertility. Males are infected with COVID-19 at a higher rate than females. As a result, some data suggest that this viral infection might affect the male reproductive system. The probable causes for male genital tract abnormalities in COVID-19 are: 1) high expression of angiotensin-converting enzyme 2 in the testes;2) SARS-CoV-2 infection indirectly induces immune response in the testes;3) SARS-CoV-2 directly damages male genital cells by virus-receptor binding activity;4) fever in SARSCoV-2 infected males may cause damages to testicular cells;5) testosterone level decreased in SAR-CoV-2 infected males;6) males are more susceptible to COVID-19 than females, which may be due to differences in the physiology of the genital tract. This review seeks to offer some insights into the potential causes of COVID-19 that affect the male reproductive system, as well as future prospect on this issue.
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Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have antitumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients' prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily;two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in >10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease.
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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.
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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.
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Introduction & Objectives: COVID-19 infection is hypothesized to have a potentially negative effect on male fertility through direct damage to the testes. The current trial is aimed at investigating the effect of SARS-CoV-2 on fertility and determining if viral bodies directly damage testicularfunction.Materials & Methods: This prospective study included controls comprising healthy participants and cases of patients suffering from pneumoniabased on chest CT and a positive of SARS-CoV-2 throat swab exhibited only moderate symptoms in accordance with the WHO classification.Extensive epidemiological, clinical, laboratory (hormonal levels, etc.) and ultrasound data (color doppler ultrasound of the scrotum) were collected. Asperm examination was performed in cases during their COVID-19 related hospital stay and 3 months after the discharge home. We also assessedthe testicles of COVID-19 patients who died of their disease (n=20) obtained during autopsies.Results: A total of 88 participants were included (44 controls and 44 cases). Blood testosterone levels were below normal (local reference values,5-50 nmol/ml) in 27.3% of the cases (12/44). The mean level (7.3±2.7 nmol/ml) was lower than that in the healthy controls (13.5±5.2 nmol/ml,p<0.001). At 3 months after discharge, the level returned to normal (13.7±4.5 nmol/ml) and was no different from that of the controls. An increase inLH and FSH was also detected compared to the healthy controls (p=0.047 and p=0.002). The spermogram revealed decreased motility in COVID-19patients (p=0.001), and higher number of immobile sperm (during COVID-19 – 58.8% and at 3 months 47.4%, p=0.005). All these parametersreturned to normal at 3 months after discharge. As for pathology findings, in the majority of autopsies (18/20) structural disorders of the testiculartissue, with signs of damage to germ cells were observed.Conclusions: COVID-19 and its treatment significantly affect hormone levels and sperm quality during the disease. Postmortem examinationconfirms inflammation and viral infiltration of the testicles. However, in those who had moderate to severe disease, decline in hormone levels andsperm quality was transient with values returning to baseline at 3 months
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AIM: Levamisole, an antiparasitic drug, was reported to have positive effects in various clinical trials in the treatment of COVID-19. However, the number of studies on the effects of levamisole on the reproductive system and sexual behavior in male rats is limited. The present study aimed to investigate the possible effects of levamisole on sexual behavior, testicular histopathology, serum gonadotropin, and testosterone levels in male rats. METHODS: Twenty male Sprague-Dawley rats were divided into two groups as control and levamisole were used. Rats were given levamisole (2 mg/kg) dissolved in distilled water for 30 days, while only distilled water was administered to the control group by oral gavage. Finally, sexual behavior tests (SBT) were performed for 30 min. Then, the animals were decapitated, blood samples and testis tissues were taken. The Bax, Hsp70 and cytochrome c immunohistochemistry staining were performed in testis tissues, and gene expression levels were measured by real-time PCR. The luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were measured by ELISA in serum samples. RESULTS: In SBT parameters, mount latency (ML, p<0.001), intromission latency (IL, p<0.01), and the postejaculatory interval (PEI, p<0.01) were significantly prolonged. Also, the copulatory rate (CR, p<0.05) was significantly reduced. Serum LH, FSH, and testosterone levels did not change. In the histopathological stainings, irregularities in the seminiferous tubule germinal epithelium, congestion, edema in the interstitial area, and metaphase arrest in some spermatocytes were detected in the levamisole group (p<0.001). Levamisole treatment also significantly increased cytochrome c, Bax, and Hsp 70 immunoreactivities and Bax (p=0.05) and Hsp 70 (p<0.01) gene expression levels in testicular tissue. CONCLUSION: Levamisole may decrease sexual motivation and copulation efficiency. Also, it may adversely affect testicular histopathology in male rats.
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BACKGROUND: New coronavirus infection (Covid-19) in patients with diabetes type 2 mellitus (DM) often has severe clinical course and manifestation. This comorbidity is a reasonable indication for vaccination. Male patients are often concerned about the vaccination impact on their fertility, so the current research of this issue seems to be essential and relevant. AIMS: To evaluate the quality of ejaculate in type 2 diabetes mellitus (DM) patients, vaccinated by GamCovidVac (Sputnik V). MATERIALS AND METHODS: The pilot observational prospective study included 30 males with type 2 diabetes mellitus (DM). The study continued from February 2021 till June 2021. The research design involved medical history analysis, glycated hemoglobin (HbA1c) tests, total testosterone level in blood measurement, semen analysis (sperm count test). Group comparison was performed by Wilcoxon Signed Ranks Test. The differences were considered statistically significant at p<0.05. RESULTS: After vaccination 19 patients (63%) demonstrated a temperature rise which lasted for 2 days;26 patients (87%) complained of tenderness in the injections site which lasted up to 5 days. Though a few patients reported general somatic side effects after the vaccination, there have been no statistically significant deviations in sperm count, viability, function and morphology. The levels of glycated hemoglobin and total testosterone remained unchanged. CONCLUSION: The study revealed no negative impact of GamCovidVac on ejaculate quality, total testosterone level and compensation of carbohydrate metabolism.