Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

The Effect of COVID-19 on the Human Reproductive System: A Review Study

Background: Evidence reveals that COVID-19, in addition to impacting the respiratory system, affects other organs, including the male and female reproductive systems. The purpose of this study was to examine the impact of COVID-19 on the human reproductive system. Method(s): Data were collected in SID, Science Direct, PubMed, and Google Scholar databases. The Keywords including COVID- 19, reproductive system, fertility, and factors related to mesh term utilization and Boolean strategy were used. Papers from 2019 to 2022 were extracted. Finally, out of 58 searched articles, 20 articles related to the purpose of the study were reviewed. Result(s): The results were organized into two categories. The first category deals with the effect of COVID-19 on the female reproductive system including Sleep disorders following quarantine on gonadotropin release and its effect on the ovaries and menstrual cycle, preterm delivery, increased cesarean delivery, the possibility of intrauterine infection of the fetus and dysfunction of the reproductive glands. The second category concerns the effect of COVID-19 on the male reproductive system including abnormal semen quality, possible effect on gonocyte differentiation in the early stages of spermatogenesis, negative effect on spermatogenesis, testicular dysfunction, and changes in testosterone concentration by increasing serum LH, testicular inflammation, decreased sperm concentration in semen, impaired sperm motility, dysfunction of the reproductive glands, significant damage to the seminiferous tube, swelling of Sertoli cells, decreased Leydig cells, significant disorder on semen volume and impaired sperm morphology. Conclusion(s): The findings revealed that COVID-19 has an impact on various aspects of the human reproductive system. Midwives and gynecologists should alleviate couples' fears about infertility by recognizing these cases and offering suitable counseling to couples infected with COVID-19.

Immunohistochemical Analysis of Spermatogenesis in Patients with SARS-CoV-2 Invasion in Different Age Groups.

Based on studies that focused on the effect of SARS-CoV-2 on human tissues, not only pulmonary invasion was revealed, but also impaired testicular function. Thus, the study of the mechanisms of influence of SARS-CoV-2 on spermatogenesis is still relevant. Of particular interest is the study of pathomorphological changes in men of different age groups. The purpose of this study was to evaluate immunohistochemical changes in spermatogenesis during SARS-CoV-2 invasion in different age groups. In our study, for the first time, a cohort of COVID-19-positive patients of different age groups was collected, and the following were conducted--confocal microscopy of the testicles and immunohistochemical evaluation of spermatogenesis disorders in SARS-CoV-2 invasion with antibodies to the spike protein, the nucleocapsid protein of the SARS-CoV-2 virus, and angiotensin convertase type 2. An IHC study and confocal microscopy of testicular autopsies from COVID-19-positive patients revealed an increase in the number of S-protein- and nucleocapsid-positively stained spermatogenic cells, which indicates SARS-CoV-2 invasion into them. A correlation was found between the number of ACE2-positive germ cells and the degree of hypospermatogenesis, and in the group of patients with confirmed coronavirus infection older than 45 years, the decrease in spermatogenic function was more pronounced than in the cohort of young people. Thus, our study found a decrease in both spermatogenic and endocrine (Leydig cells) testicular functions in patients with COVID-19 infection. In the elderly, these changes were significantly higher than in the group of young patients.

Microbiology and immune mechanisms associated with male infertility.

Up to 50% of infertility is caused by the male side. Varicocele, orchitis, prostatitis, oligospermia, asthenospermia, and azoospermia are common causes of impaired male reproductive function and male infertility. In recent years, more and more studies have shown that microorganisms play an increasingly important role in the occurrence of these diseases. This review will discuss the microbiological changes associated with male infertility from the perspective of etiology, and how microorganisms affect the normal function of the male reproductive system through immune mechanisms. Linking male infertility with microbiome and immunomics can help us recognize the immune response under different disease states, providing more targeted immune target therapy for these diseases, and even the possibility of combined immunotherapy and microbial therapy for male infertility.

Post COVID-19 infection associated IgA vasculitis

Background/Purpose: IgA vasculitis is the most common vasculitis affecting children. Vasculitis can be associated with the inflammatory process following infections, involving single or multiple organs. COVID-19 associated vasculitides have been reported variously, mostly Kawasaki-like features, livedo reticularis and rarely cutaneous small vessels vasculitis. Recently, there have been reports of IgA vasculitis following COVID-19 infection in children, although data among Asians are scarce. Method(s): Case report Results: We herein report a case of a previously healthy 6-year- old Thai boy with history of COVID-19 infection 4 weeks earlier, with only mild upper respiratory tract symptoms treated by a 5 day-course of favipiravir and supportive medication. He presented with rash over both lower limbs with difficulty to bear weight for a week. He denied fever, abdominal pain, nausea, vomiting, or any abnormal urinary symptoms. Physical examination revealed palpable purpura distributed on both lower legs with pain in his left foot and difficulty in bearing weight. His blood pressure was unremarkable for age at 97/67 mmHg. The initial investigations showed complete blood count with white cell count of 8.9 x 103/muL (neutrophils 47.3% and lymphocytes 42.4%), hemoglobin of 13.6 g/dL, which had no anemia for his age and platelet count of 297 x 103/muL. His urinalysis showed 2-3 red blood cells and 0-1 white blood cells per high power field without proteinuria and normal renal function. The erythrocyte sediment rate was 11 mm/hr and c-reactive protein was 3.9 mg/L, which were in normal range. He was diagnosed as IgA vasculitis and non-steroidal anti-inflammatory drug was prescribed to alleviate arthralgia of left foot. A week later, he revisited due to pain and swelling at his left scrotum. He was diagnosed as orchitis, one of the clinical manifestations of IgA vasculitis that can occur in boys. He had ongoing palpable purpura on the legs but pain at the left foot subsided. He then received oral prednisolone for the indication of orchitis at the dosage of 1 mg/kg/day with subsequent tapering for total duration of 3 weeks. All of his symptoms completely resolved. Conclusion(s): We present the interesting case of a Thai boy clinically diagnosed with IgA vasculitis following COVID-19 infection, having the clinical manifestations of palpable purpura, arthralgia, and orchitis. There are very limited data about post COVID-19- associated IgA vasculitis in children, especially in the Asian population. We would like to highlight this condition for physicians and to raise the awareness in the COVID-19 era.

Orchitis as an unusual manifestation in multisystem inflammatory syndrome in children

This is a case report about an 8-year old boy who presented with complaints of fever for 5 days, loose stools, abdominal pain, and erythema of the palms and soles for 3 days. There was a history of short duration fever in all his family members 1 month back, but none of them were tested for COVID-19. On admission, the patient was febrile and had erythematous extremities. There was no organomegaly. He presented with hypotensive shock which was managed with fluid boluses and inotrope support. Fever workup including cultures were negative. His COVID-19 antibody was positive (16.17 index units). Inflammatory markers were elevated: ESR=50 mm/h=;C reactive protein=51 mg/dL;ferritin=>1000 ng/mL;D dimer=8260 ng/mL. Echocardiogram was normal and he was managed with intravenous immunoglobulin due to meeting the criteria for multisystem inflammatory syndrome (MISC) in children. The patient's fever subsided within 48 hours and his inflammatory markers showed declining trend. On the third day of becoming afebrile, the child complained of swelling, pain, and redness of right scrotum. There was no recurrence of fever, nor parotid swelling associated with orchitis. On examination, the right testis was enlarged, tender, located in the normal anatomic position with an intact ipsilateral cremasteric reflex. testicular tension was ruled out by ultrasound doppler. The unilateral orchitis was managed with supportive measures and subsided by 48 hours.

Male Reproductive Tract Involvement and Sperm Parameters in SARS-CoV-2 Patients: A Systematic Review and Meta-Analysis.

PURPOSE: There is a growing concern regarding the impact of SARS-CoV-2 infection on the male reproductive tract due to ACE2 receptor expression, however, its impact remains unclear. We performed this review to evaluate whether SARS-CoV-2 infection affects the male reproductive system. MATERIALS AND METHODS: We conducted a search in the Embase, Scopus, and MEDLINE databases, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Eligible studies comprised articles reporting viral RNA presence in semen, sperm parameters, and orchitis or orchiepididymitis occurrence in SARS-CoV-2 patients. Observational studies' quality was determined using the Newcastle-Ottawa Scale (NOS). Case reports were assessed using the Joanna Briggs Institute (JBI)'s checklist. RESULTS: A total of 32 relevant articles were included. Viral RNA was found in 7% of infected patients' semen (95% CI, -0.01 to 0.15) from 3 studies. There were also only 7% of patients with orchitis or orchiepididymitis clinical manifestations (95% CI, 0.05-0.10). The semen volume and concentration were 2.34 mL (95% CI, 1.87-2.81) and 51.73 million/mL (95% CI, 31.60-71.85). The progressive and total motility percentages were 36.11% (95% CI, 28.87-43.35) and 43.07% (95% CI, 28.57-57.57), respectively. The morphology was 6.03% (95% CI, -1.05 to 13.10). There is a difference in semen volume between moderate and severe infections (MD, 0.52; 95% CI, 0.27-0.76; p<0.0001) and concentration between mild and moderate (MD, 18.74; 95% CI, 1.02-36.46; p=0.04), mild and severe (MD, 43.50; 95% CI, 13.86-73.14; p=0.004), as well as moderate and severe (MD, 22.25; 95% CI, 9.33-35.17; p=0.0007). CONCLUSIONS: SARS-CoV-2 infection may result in decreased sperm concentration in severe cases and the mechanism relates to potential reproductive tract inflammation. The absence of large viral RNA detection in the semen indicates a systemic effect, although this is largely unproven.

Safety, pharmacokinetics, and antiviral activity of the S-antigen Transport Inhibiting Oligonucleotide Polymers (STOPS) drug candidate ALG-010133 in subjects with chronic hepatitis B

Background and aims: To evaluate the safety, pharmacokinetics (PK) and antiviral activity of ALG-010133, a STOPS molecule designed to reduce hepatitis B S-antigen (HBsAg) in chronic hepatitis B (CHB) patients. Method: This was a 3-part, multicenter, double-blind, randomized, placebo-controlled study. In Parts 1 and 2, single and multiple subcutaneous (SC) doses of ALG-010133were generallywell tolerated in healthy volunteers (Gane et al, EASL 2021). Part 3 evaluatedweekly SC doses of ALG-010133 or placebo × 12 weeks in virologically suppressed Hepatitis B e-antigen (HBeAg) negative CHB subjects (N = 10/cohort;8 active:2 placebo). Reported here are preliminary blinded Part 3 safety, PK, and antiviral data;unblinded data will be presented at the conference. Results: 31 CHB subjects completed dosing and follow-up in Cohorts 1 (120 mg;N = 10), 2. (200 mg;N = 10), and 3 (400 mg;N = 11). Most subjects were male (61%) and 48% were white, with mean age 48 years, mean BMI 26.1 kg/m2 and baseline HBsAg across cohorts of 3.6 to 3.7 log10 IU/ ml. Therewas 1 unrelated serious treatment emergent adverse event (TEAE) (hospitalization for orchitis) and 1 unrelated TEAE (COVID-19 infection) resulting in premature study drug discontinuation. All TEAEs were Grade 1 or 2 in severity, except for 1 Grade 3 TEAE of injection site erythema (severity based only on surface area criteria of ≥100 cm2;required no treatment and resolved despite continued study drug dosing) and the aforementioned TEAE of orchitis (Grade 3). There was no dose relationship to severity or frequency for any TEAE. The most common (≥3 subjects) TEAEs were injection site erythema (n = 5), increased ALT (n = 4), injection site bruising (n = 4), increased AST (n = 3), and injection site pruritus (n = 3);none were assessed as clinically concerning. Although treatment-emergent ALT and AST elevations (n = 13) were observed, all were Grade 1 (<2.5x upper limit of normal [ULN]) or 2 (≥2.5 to <5x ULN) and none led to premature study drug discontinuation or were associated with symptoms or evidence of liver dysfunction. There were no other clinically significant lab abnormalities. No clinically significant physical examinations, vital signs, or ECG abnormalities were reported. Plasma ALG-010133 exposures increased more than dose proportionally between the 120 to 400 mg dose levels, with moderate variability and minimal accumulation. Compared to baseline, the magnitude of HBsAg decline at Week 12 was <0.1 log10 IU/ml for placebo and across all ALG-010133 dose levels, including the projected efficacious dose level of 400 mg (estimated to maintain total liver exposures >3x EC90 for HBsAg inhibition). Conclusion: ALG-010133 was safe and well tolerated with predictable PK properties when given to CHB subjects as multiple SC doses of up to 400 mg. No meaningful HBsAg reduction was observed across all cohorts. Further clinical development of ALG-010133 has been discontinued.

MYCOPLASMA GENITALIUM TESTING: A VICTIM OF TENDERING AND COVID?

Introduction Mycoplasma Genitalium is a relative newcomer to sexual health clinics;but is testing now routinely embedded in practice? In a clinic victim to a traumatic tendering process and then to the pandemic, a full audit cycle revealed the truth and some unexpected findings. Methods 1. Patient list based on GUMCAD codes for: Mycoplasma Genitalium, Pelvic inflammatory disease, Non-specific urethritis, epididymo-orchitis. Cycle 1 looked retrospectively at March-August 2021 (6 months) comparing findings to BASHH standards. 2. Intervention: Presentation of audit findings and a teaching session on Mycoplasma Genitalium 3. Retrospective second cycle audit looking at October 2021- January 2022 (3 months). Results Cycle 1: • 53 patients tested. Of the 11 women tested, 9 were mycoplasma contacts. • 41% NSU and 10% PID presentations were tested • 14 cases positive (26%), 25% had test of cures Cycle 2: • 68 patients tested. • 64% NSU and 46% PID presentations tested • 12 cases positive (18%), 100% contacted for test of cure. Other findings • Testing is dependent on clinician: Nurses met guidelines in 100% of patients, GUM doctors 64% and GP Trainees 50%. Health advisors contacted 100% of patients for test of cures. • No routine resistance testing provided, but 17% had documented resistance, 33% clinical resistance Discussion Mycoplasma was overlooked with tendering and covid no doubt playing a part. This audit highlighted the deficiencies, but interventions improved testing;nurses effectively adopting it into routine practice whilst uptake from doctors was limited. Resistance levels are concerning and support the need for routine resistance testing.

Sonographic findings of COVID-19 related acute scrotal infection and associations with clinical-laboratory data.

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, patients present to hospitals with a wide range of symptoms. Some of these symptoms include acute orchitis and epididymitis. The goal of this research is to see if COVID-19 infection and scrotal infection are associated. MATERIALS AND METHODS: Patients with a COVID-19 (+) who agreed to a scrotal ultrasound (US) examination were studied prospectively in a tertiary care center between October 2021 and February 2022. The severity of the disease was used to divide patients into groups. Patients diagnosed with acute scrotal infection based on scrotal ultrasonography findings were compared in these groups, as were their age, comorbidities, and laboratory data. RESULTS: The median age of the 213 participants was 61.7 ± 8.3. During the ultrasonographic examination of the patients, 15 (7%), 8 (3.7%), 17 (7.9%), and 40 (18.7%) were diagnosed with acute orchitis, acute epididymitis, acute epididymo-orchitis, and scrotal infection, respectively. Acute scrotal infection was far more common in patients with a higher clinical severity of the disease. The patients' comorbidities were also assessed, and it was discovered that they were statistically more common in the same group. CONCLUSIONS: Even if there are no clinical symptoms, ultrasonography can help detect acute scrotal infection in COVID-19 patients. Furthermore, in groups with higher clinical severity, this association is more likely to be seen. It is critical to understand this in order to avoid complications.

Quarterly report of investigations of suspected exotic diseases: July to September 2021

Exotic pest and disease investigations are managed and reported by the Ministry for Primary Industries' (MPI's) Diagnostic and Surveillance Directorate. This article presents a summary of investigations of suspect exotic and emerging pests and diseases in New Zealand during the period from July to September 2021.

COVID-19 VACCINATION IS ASSOCIATED WITH A DECREASED RISK OF ORCHITIS AND/OR EPIDIDYMITIS IN MEN

INTRODUCTION AND OBJECTIVE: Vaccine hesitancy is a major public health obstacle to fighting the ongoing COVID-19 epidemic. Due to studies that show COVID-19 infection can affect sperm parameters and lead to orchitis, the public are concerned about how the COVID vaccines may impact male reproduction. In this study, we investigated the association between COVID-19 vaccination and risk of developing orchitis and/or epididymitis outcomes in a cohort of men using a large, US-based, electronic health record database (TriNetX). METHODS: We queried the database for male patients ages 12 years and older who received a single-dose COVID-19 vaccine or at least 1 dose of a 2-dose regimen using specific ICD-10 medication and procedure codes and compared them to a cohort of men who had no record of any COVID-19 vaccination in their health record. The outcome for analysis was diagnosis of orchitis and/or epididymitis (ICD-10-CM: N45-N45.4, N51) between 1-9 months after the index event of COVID-19 vaccination. The two cohorts were balanced for the following potentially confounding variables through propensity score matching: age at index event, race, urinary tract infection, and unspecified sexually transmitted disease. We determined the association between COVID-19 vaccination and orchitis and/or epididymitis using logistic regression analysis with statistical significance assessed at p<0.05. RESULTS: We identified 663,774 men in the database who had received at least one dose of a COVID-19 vaccine, and 9,985,154 who did not. Prior to propensity score matching, 0.051% of men in the vaccinated cohort and 0.083% in the unvaccinated cohort received a diagnosis of orchitis and/or epididymitis in the time window (OR =0.619;95% CI: 0.556 - 0.690;p<0.0001). After balancing for potentially confounding variables, the COVID-19 vaccine remained protective against development of orchitis and/or epididymitis (OR =0.568;95% CI: 0.497 - 0.649;p<0.0001). CONCLUSIONS: In this retrospective cohort study, we demonstrated that receiving a COVID-19 vaccine is associated with a decreased risk of developing orchitis and/or epididymitis. These findings have important implications in the counseling of patients that are hesitant to receive the COVID-19 vaccine and refute misinformed claims on social media regarding the effect of the vaccines on male fertility.

WHOLE EXOME SEQUENCING IDENTIFIES A RARE NONSENSE MUTATION IN NACAD AS A POSSIBLE CAUSE OF COVID ORCHITIS IN BROTHERS

OBJECTIVE: This project sought to uncover genetic explanations as to why certain men face increased susceptibility to developing COVID orchitis. Our goal was to identify genetic variants associated with COVID orchitis in a group of patients, aided by whole-exome sequencing and protein phenotyping of affected patients. MATERIALS AND METHODS:We identified and examined six COVID- 19 patients who all were confirmed with polymerase chain reaction (PCR), including three COVID-19 (+) men without orchitis (controls) and three COVID (+) men with orchitis (bilateral testicular pain for at least 5 days around the time of testing PCR positive). Of note, among the three men with COVID-19 who had orchitis, two of them were siblings.DNA extraction and whole exome sequencing were performed on blood using the QIAmp blood maxi kit on five of the six patients. Variants were prioritized by being shared between the three patients affected with orchitis, absent in controls, and introducing nonsense, frameshift, splicing or non-synonymous amino acid changes and less than 10% in population prevalence. Based on WES findings, DuoSet® Human ACE2 reagent kit 2 (catalog number: DY933- 05) was purchased from R&D Systems, USA, and used to measure the level of soluble ACE2 in the plasma samples. RESULTS: The average age of the men in the study was 25 years old. The average duration of COVID symptoms (fever, sore throat, cough, body aches) were 7 days. Among the men who developed bilateral testis pain, the symptoms lasted for an average of 22 days. The median sperm concentration and sperm motility was 19 million/cc and 60% around 3 months after original infection. A list of 16 variants was generated that found to be shared between the two siblings with COVID orchitis along with the unrelated subject with COVID orchitis, and not present in the two controls. Among the 16 variants, a nonsynonymous non-frameshit deletion in NACAD variant on chromosome 7 with a frequency of 3.9% prevalence in ExAC was prioritized based on known involvement in the ACE2 pathway, read depth, and genotype quality. Phenotypically, we found that circulating levels of solubleACE2 was 3.72 ng/ml among men who had COVID orchitis and was lower than men who developed COVID without orchitis. CONCLUSIONS: We observed a stop mutation in NACAD in 2 brothers and 1 unrelated man who developed COVID orchitis. Interestingly, we found lower circulating ACE2 serum levels in both brothers with orchitis and the one nonrelated orchitis subject but normal serum levels in all controls. NACAD when involved with cellular ability to shuttle out ACE2 becomes critical for COVID symptomatology. With decreased transcellular and extracellular transport of ACE2 being possible in subjects with the gene mutation, it can be postulated more ACE2 will be found intracellularly leading to increased cellular entry of SARS CoV-2 and possibility of orchitis sequelae. IMPACT STATEMENT: These findings provide an explanation as to why genetic variations can lead to some patients developing comorbidities such as orchitis from COVID-19.

A scoping review of SARS-CoV-2 and male infertility: Concerns and future prospects

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.

Does SARS-CoV-2 Affect Male Urogenital System?

BACKGROUND: Widely known facts about Sars-Cov-2 infection's impact on urogenital system may play a relevant role in under-standing, diagnosing, and preventing male urological disorders. Sars-CoV-2 attacks the vascular endothelium of the entire organism; therefore, infection complications are visible in various organs. Relatively small number of original studies are available on Sars-CoV-2 infection and the effect on the reproductive system and fertility in men. The vast majority of publications focus only on discussing the effects of COVID-19 infection on just one aspect of male urology or fertility. OBJECTIVES: The aim of this review was to present the current understanding of the effects of COVID-19 infection on the male genitourinary system in the context of nephrological and reproductive system complications in men, considering the potential pathomechanisms causing significant nephrological disorders in the course of viral infection, as well as long-term effects of Sars-CoV-2 infection. We tried to make clinicians aware of urogenital complications in the course of COVID-19 occurrence and encourage them to create preventive procedures. METHODS: The article presented has been classified by us as "review". Of course, when searching for publications and making their critique, we focused primarily on the words: "Sars-CoV-2", "male urogenital system", "male infertility", "lower urinary tract symptoms". Therefore, there was no explicit and rigorous work selection methodology. Search strategies were based on the experience of the authors of the work. In order to select articles for the systematic review, literature searches were conducted on PubMed (https://pubmed.ncbi.nlm.nih.gov) using the following keywords: "Sars-CoV- 2" AND "male urogenital system" OR "male infertility" The search results were retrieved and manually screened for duplicate removal. Then abstracts and titles were checked for relevance. The articles were selected if they met the following inclusion criteria: human studies, focus on Sars-CoV-2 and male urogenital system or male infertility, published from 2020 to 2021, written in English, free full-text available. We included clinical trials, meta-analyses, randomized controlled studies, reviews, systematic reviews. RESULTS: After the literature search, a total of 267 articles were retrieved, including 153 reviews, 53 systematic reviews, and 61 original articles. Eventually, after abstract and title screening, 2 original articles, 29 reviews, and 8 systematic reviews were accepted. In our review paper, we presented data from 2 systematic reviews, 17 reviews, 2 meta-analyses, 1 case study, and 18 original articles, including 3 animals studies, 2 in vitro studies, and 14 human studies. CONCLUSION: Serious concerns for urologists among COVID-19 patients should be mainly orchitis, male infertility, priapism, erectile dysfunction, and lower urinary tract symptoms. It seems that the conclusions drawn should be treated with caution because, as mentioned above, in a pandemic, urinary complications are underdiagnosed and there are too few clinical trials and case reports.

Potential effects of COVID-19 on reproductive health: A mini review

Coronavirus disease 2019 (COVID-19) is now a major public health problem worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is extremely strong. One major target of the virus is the lung, which can lead to death due to the development of respiratory distress syndrome and even multiple system organ failure. The possible pathophysiology by which SARS-CoV-2 affects the object is by way of the receptor, angiotensin-converting enzyme 2 (ACE2). From the study of the viral structure and infection mechanisms, researchers have discovered that the ACE2 acts as a receptor for SARS-CoV-2. According to previous studies, ACE2 is one of the key enzymes in the RAS system. Physiological functions can be found in angiosarcomas and in the kidney, liver, intestine and so on. Whether SARS-CoV-2 infection leads to male fertility impairment has recently received attention. Nevertheless, the association between SARS-CoV-2 infection and reproductive health is currently poorly understood. Using key words including “SARS-CoV-2”, “reproductive health”, “ACE2” and “2019-nCoV”, we retrieved original articles and reviews from the PubMed and WEB OF SCI databases published before December 16, 2020 and performed a thorough review of them. Compared with females, we discovered that infected person with SARSCoV-2 was higher in males. Men who were infected with SARS-CoV-2 may be easy to suffer from impaired reproductive health. These investigations would help for a comprehensive grasp of the relationship between SARS-CoV-2 infection and reproductive health.

Atypical presentation of COVID-19: Chronic bilateral testicular pain with lower extremity peripheral polyneuropathy, case report.

In context of COVID-19 pandemic, there has been different presentations of the infection. The relationship of testicular pain with COVID-19 has not been extensively studied. We present a 31 years old male, with SARS-COV-2 infection, repeatedly consulting for intermittent bilateral testicular pain. Two months later he reported acute loss sensibility and pain in extremities, being diagnosed with axonal fine fiber polyneuropathy. Although the presence of SARS-COV-2 in testis remains controversial, there is a potential orchiepididymitis risk due to viral binding to ACE2 receptor in testicle, and also could induce systemic vasculitis as another possible cause of orchitis.

Testicular injury during SARS-CoV-2 infection may be neglected: An assessment from scRNA-seq profiling and protein detection of angiotensin-converting enzyme II.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is outbreaking globally. SARS-CoV-2 invades host cells via angiotensin-converting enzyme II (ACE2) and causes multiple-organ injury. Autopsy studies indicated that the testis of patients with COVID-19 exhibited various degrees of spermatogenic cell reduction and injury, but the composition of ACE2-expressing cells and their proportion in the testes have remained to be determined. Recent clinical evidence suggested that the ratio of male sex hormones in males with COVID-19 was significantly changed. The present study aimed to explore whether SARS-CoV-2 is able to damage the male reproductive system. For this, the ACE2-expressing cell composition and proportion in male testes were analyzed using single-cell RNA sequencing (RNA-seq) datasets downloaded from the Gene Expression Omnibus (GEO) database and immunohistochemical (IHC) staining. The single-cell RNA-seq data indicated that ACE2 mRNA was highly expressed in myoid cells, Leydig cells and spermatogenic cells, accounting for 5.45, 1.24 and 0.423% of adult testicular cells. ACE2 mRNA-expressing Sertoli cells, spermatogenic cells and myoid cells accounted for 5.00, 0.56 and 0.73% of infant testicular cells. IHC demonstrated that ACE2 protein was also highly expressed in testicular tissues. In conclusion, the present results demonstrated that testicular injury may be missed by clinicians in patients with COVID-19 and male reproductive function should be closely followed up.