Mumps resurgence in India in the decade 2014-2023: A Trend and Geospatial Analysis (preprint)

Background Mumps, caused by the paramyxovirus, primarily affects children and adolescents and presents with parotiditis. Complications such as orchitis and meningitis can occur, especially in young adult males and vaccination reduces complications. Global mumps cases surged in the past decade, including regions like North and South America, Australia, and Iran. In India, a recent surge in mumps cases was reported in 2023. The current analysis was performed to assess the burden and trend of mumps in India over the last decade and geographical variations in its burden across India.Methods Using the weekly outbreak reports of Integrated Disease Surveillance Programme(IDSP) for the period of 2014 to 2023, number of mumps cases and outbreaks in India were plotted to see the trend of mumps in past 10 years. State wise spatial distribution of the number of mumps cases and outbreaks were also performed using QGIS for 2023 to ascertain geographical variation in mumps burden across India.Results Distinct peaks and troughs in mumps cases were observed, with notable increases in 2015, 2016, and 2019. Absence of reported cases in 2021 and a resurgence in 2023 were noted. Spatial analysis identified hot spots and clusters, indicating hyperendemic areas. State-wise wide variations were evident, with some states reported disproportionately higher number of outbreaks like Jammu and Kashmir. The impact of COVID-19 on mumps incidence was seen, with a decrease in 2020 and an increase in 2023.Conclusion Total number of mumps outbreaks and cases were reported to be highest in 2023 which is alarming and emphasizes the need for inclusion of mumps containing vaccine in form of MMR vaccine in the Universal immunization Programme (UIP) of India along with strengthening the mumps surveillance. These findings also underscore the importance of state-specific analyses and evidence-based interventions to address mumps outbreaks effectively in India.

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.

A 7-year-old Boy with Orchitis after COVID-19 Infection (preprint)

Although most manifestations of coronavirus infection in children are mainly related to the respiratory and gastrointestinal organs, involvement of other organs has also been seen with less prevalence. Because of the expression of virus receptors in male genitalia, this system is regarded as a potential target for this virus.

COVID-19 vaccination is associated with a decreased risk of orchitis and/or epididymitis in men.

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 the effect of the COVID vaccines on 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. After balancing for confounding variables, we found that receiving at least 1 COVID-19 vaccine is associated with a decreased risk of developing orchitis and/or epididymitis.

Whole Exome Sequencing Identifies a Rare Mutation in NACAD as a Possible Cause of COVID Orchitis in Brothers.

COVID orchitis (testicular pain) is reported in 10-15% of men with long COVID. We identified 2 siblings with COVID orchitis and hypothesized that genetic mutations are associated with susceptibility. Blood samples from 5 COVID-19 (+) men, three of whom had orchitis were evaluated by whole-exome-sequencing. A rare deletion on chromosome 7 was found in NACAD among the 3 men with orchitis. Interestingly, circulating ACE2 levels was decreased in men with COVID orchitis. This pilot study generated the hypothesis that men who develop COVID orchitis could have underlying genetic variants and altered levels in circulating ACE2 that may increase their risk.

Ultrasound Imaging Findings of Acute Testicular Infection in Patients With Coronavirus Disease 2019: A Single-Center-Based Study in Wuhan, China.

OBJECTIVES: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, raising widespread public health concerns. Our team treated hospitalized patients with COVID-19 in Wuhan, where the outbreak first began, and we suspected that SARS-CoV-2 may cause testicular infection in male patients. We conducted this study to explore that observation. METHODS: We enrolled male patients with a confirmed diagnosis of COVID-19 and performed a bedside ultrasound (US) examination of the scrotum, focused on findings of acute inflammation such as tunica albuginea thickening, enlargement and heterogeneous echogenicity of the testis, epididymis, or both, an abscess, scrotal wall edema, and hydrocele. Then we compared the proportions of observed epididymo-orchitis in patients from different age groups and COVID-19 severity groups. RESULTS: A total of 142 patients with COVID-19 were enrolled in our study, and 32 (22.5%) patients had acute orchitis, epididymitis, or epididymo-orchitis on scrotal US imaging, according to the diagnosis criteria. The observed risk of acute scrotal infection increased with age, with the incidence reaching 53.3% in men older than 80 years. We also observed that men with severe COVID-19 had a significantly higher possibility of epididymo-orchitis compared to the nonsevere COVID-19 group (P = .037). CONCLUSIONS: This study shows US imaging evidence that SARS-CoV-2 may cause infection of the testis or epididymis, and the risk is worthy of the attention of clinicians.

Testicular pathology in fatal COVID-19: A descriptive autopsy study.

BACKGROUND: Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. OBJECTIVE: To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. MATERIALS AND METHODS: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. RESULTS: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. DISCUSSION AND CONCLUSION: The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.

A coronavirus disease 2019 (COVID-19) patient with bilateral orchitis.

During the development of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), a myriad of complications has emerged and although rare, several genitourinary complications have been reported. The bulk of these complications have been secondary to hypercoagulable states, such as priapism. Previous SARS family infections have caused orchitis, though no adult cases of orchitis have been reported. We describe a novel case of SARS-CoV2 bilateral orchitis in a previously healthy 37-year-old male who presented for testicular pain with constitutional symptoms. Additionally, there was no epididymitis associated with the bilateral orchitis. Based on both data in SARS-CoV2 infected males and previous data from prior SARS infections, spermatocyte function may be compromised secondary to this infection. With the various symptoms associated with this virulent pathogen, we characterize the potential complications and importance of fertility follow up.

Review of COVID-19 and male genital tract.

COVID-19 pandemic leads to health challenges globally, and its diverse aspects need to be uncovered. Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. Since these cell surface receptors' expression has been disclosed within the male reproductive system, its susceptibility to being infected by SARS-CoV-2 has been summarised through this literature review. Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection. Presence of SARS-CoV-2 within semen samples and following direct viral damage, secondary inflammatory response causing orchitis or testicular discomfort and finally the amount of viral load leading testicular damage and immune response activation are among probable underlying mechanisms. Therefore, genital examination and laboratory tests should be considered to address the male reproductive tract complications and fertility issues.

Potential mechanisms of SARS-CoV-2 action on male gonadal function and fertility: Current status and future prospects.

The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin-converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS-CoV-2 are not fully elucidated. The major focus of the present studies is on the short-term complications of the coronavirus and gains importance on studying the long-term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS-CoV-2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID-19, possible formation of anti-sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS-CoV-2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID-19 along with other options such as sex-related hormones and semen analysis. Invasion of SARS-CoV-2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.

Relationship between COVID-19 and the male reproductive system.

OBJECTIVE: The objective of this review is to provide currently available information on the potential effects of coronavirus disease 2019 (COVID-19) on male fertility. MATERIALS AND METHODS: This is a mini-review. Due to the similarity between the COVID-19 and severe acute respiratory syndrome (SARS) virus, we searched for the following keywords: "SARS-CoV, male reproductive system, infertility, COVID-19, SARS-CoV-2, and orchitis". By reviewing and analyzing the literature, we analyzed the influence of temperature on sperm, the expression of angiotensin-converting enzyme 2 (ACE2) in the testes, and the impact of SARS-CoV-2 on the male reproductive system. RESULTS: SARS-CoV-2 enters the body through the ACE2 receptor. The high expression of ACE2 on the surface of spermatogonia and supporting cells in the testes, as well as the immune response caused by COVID-19, can lead to testicular spermatogenesis dysfunction and reduced sperm count. CONCLUSIONS: COVID-19 infection can affect male reproductive function, and standard treatment strategies should be established in time to help male patients infected with COVID-19.

Evaluating the impact of COVID-19 on male reproduction.

Invasion or damage of the male reproductive system is one of the reported outcomes of viral infection. Current studies have documented that SARS-CoV-2, which causes COVID-19, can damage the male reproductive system in large part by inflammatory damage caused by a cytokine storm. However, whether SARS-CoV-2 can infect the human testis directly and enter semen is controversial. Other adverse effects of SARS-CoV-2 on male reproduction are also of concern and require comprehensive evaluation. Here, we analyze the invasiveness of SARS-CoV-2 in the testis and examine reported mechanisms by which SARS-CoV-2 interferes with male reproduction. Long-term implications of SARS-CoV-2 infection on male reproduction are also discussed. It should be emphasized that although COVID-19 may induce testicular damage, a substantial decrease in male reproductive capacity awaits clinical evidence. We propose that there is an urgent need to track male COVID-19 patients during their recovery. The development of suitable experimental models, including human reproductive organoids, will be valuable to further investigate the viral impact on reproduction for current and future pandemics.

Is there any association of COVID-19 with testicular pain and epididymo-orchitis?

AIMS: This study aims to analyse the novel Coronavirus disease- (COVID-19) related testicular pain in hospitalised patients because of COVID-19 and to review as an aetiological factor for epididymitis, orchitis or both. METHODS: A total of 91 patients were included in the study. A questionnaire was formed for the questioning of testicular pain or epididymo-orchitis in patients with COVID-19. Demographics and past medical history was also recorded. Patients' neutrophil and lymphocyte counts, neutrophil-lymphocyte ratios (NLR), C-reactive protein (CRP) levels and D-dimer values were recorded. Patients with COVID-19 were divided into two groups according to absence or presence of testicular pain or epididymo-orchitis as group 1 and group 2. All results were compared for both groups. RESULTS: The median age of patients was similar in both groups. Testicular pain was occurred in 10.98% of the patients. Clinical presentation of epididymo-orchitis was diagnosed in only one patient. No statistically significant difference was reported in terms of patients' age, levels of CRP and D-Dimer or NLR and results of questionnaire form queries between the two groups (P > .05). CONCLUSION: Testicular pain was observed more frequently in hospitalised COVID-19 cases. While no inflammation marker which is related to predict of testicular pain or epididymo-orchitis was found in patients with COVID-19.

[SARS-CoV-2 infection: implications for sexual and reproductive health. A position statement of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA)]. / Infección por SARS-CoV-2: implicaciones para la salud sexual y reproductiva. Una declaración de posición de la Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA).

OBJECTIVE: The main objective of this revision is to summarize the current existing evidence of the potential adverse effects of SARS-CoV-2 on the male reproductive system and provide the recommendations of the Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA) concerning the implications of COVID-19 infection in the management of male infertilty patients and testicular endocrine dysfunction. METHODS: A comprehensive systematic literature search of the databases of PubMed, Web of Science, Embase, Medline, Cochrane and MedRxiv, was carried out. RESULTS: The presence of orchitis as a potential complication of the infection by SARS-CoV-2 has not yet been confirmed. One study reported that 19% of males with COVID-19 infection had scrotal symptoms suggestive of viral orchitis which could not be confirmed. It is possible that the virus, rather than infecting the testes directly, may induce a secondary autoimmune response leading to autoimmune orchitis. COVID-19 has been associated with coagulation disorders and thus the orchitis could be the result of segmental vasculitis. Existing data concerning the presence of the virus in semen are contradictory. Only one study reported the presence of RNA in 15.8% of patients with COVID-19. However, the presence of nucleic acid or antigen in semen is not synonyms of viral replication capacity and infectivity. It has been reported an increase in serum levels of LH in males with COVID-19 and a significant reduction in the T/LH and FSH/LH ratios, consistent with subclinical hypogonadism. CONCLUSIONS: The findings of recent reports related to the potential effects of COVID-19 infection on the male reproductive system are based on poorly designed, small sample size studies that provide inconclusive, contradictory results. Since there still exists a theoretical possibility of testicular damage and male infertilty as a result of the infection by COVID-19, males of reproductive age should be evaluated for gonadal function and semen analysis. With regard to the sexual transmission of the virus, there is not sufficient evidence to recommend asymptomatic couples to abstein from having sex in order to protect themselves from being infected by the virus. Additional studies are needed to understand the long-term effects of SARS-CoV-2 on male reproductive function, including male fertility potential and endocrine testicular function.

Prior and novel coronaviruses, Coronavirus Disease 2019 (COVID-19), and human reproduction: what is known?

OBJECTIVE: To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy. DESIGN: Review of English publications in PubMed and Embase to April 6, 2020. METHOD(S): Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications. RESULT(S): Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported. CONCLUSION(S): Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.

SARS-CoV-2 and the testis: similarity with other viruses and routes of infection.

Since the start of the latest coronavirus (SARS-CoV-2) outbreak, the number of infected individuals and cases of coronavirus disease (COVID-19) has been increasing exponentially worldwide. Of interest is existing evidence that orchitis can develop due coronavirus infection. It is therefore not unreasonable to believe that SARS-CoV-2 could be transmitted by semen. Consequently, it is of paramount importance that individuals who could potentially be infected take all possible care to mitigate the likely risk of passing on the infection through sexual intercourse.