Scrotal pain as a novel symptom of multisystem inflammatory syndrome in children (MIS-C): Report from Riyadh, Saudi Arabia.

A previously healthy child, presented with severe abdominal and scrotal pain with scrotal swelling for five days. There was associated fever, vomiting, and diarrhea. There was history of COVID-19 infection in the previous month. The patient was febrile (39°C), and in pain. His other vitals were unremarkable. Testicular torsion and appendicitis were ruled out by ultrasound. Abdominal CT scan showed signs indicating terminal ileitis. His MIS-C panel revealed elevated inflammatory markers and cardiac enzymes and positive SARS-CoV-2 IgG levels. All cultures and RT-PCR COVID-19 were negative. Echocardiogram showed only minor mitral and tricuspid regurgitation. The patient was diagnosed as a case of MIS-C. and recovered completely on management. Our patient showed an inexplicable previously unreported complaint of scrotal pain and swelling as a symptom of MIS-c. Further research tackling MIS-C's different presentations and comparing the efficacy of the different treatment methods will help us better manage this disease.

Presentations of the Acute Scrotum During the COVID-19 Pandemic: Experiences of a Non-urological Centre.

INTRODUCTION: Testicular torsion is a time-sensitive surgical emergency. Assessment of the acute scrotum warrants rapid surgical review and low threshold for surgical intervention.  Materials and methods: A retrospective cohort study was undertaken for a three-month period during the first wave of the 2020 COVID-19 pandemic and the corresponding period in 2019. Data were collected for all scrotal explorations undertaken at our non-urological centre during this time. RESULTS: Sixteen scrotal explorations were performed from April to June 2019, one had testicular torsion (6.25%). Forty-one explorations were performed from April to June 2020, nine had testicular torsion (21.95%). The most common diagnosis was epididymitis or epididymo-orchitis in 2019 and 2020 (27% and 37.5%, respectively). Sixty-two percent of patients presented within 12 hours in 2019 compared to only 37% during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSION: This study found an increase in the number of patients presenting with acute scrotal pain triggering surgical intervention and the number of patients with testicular torsion. This is likely to reflect a decrease in patients able to access primary care assessment but may also be related to COVID-19. There was a marked delay in the presentation which has significant implications for testicular viability.

Hemophagocytic Lymphohistiocytosis after COVID-19 Vaccination: A Case Report

Aim and background: Cases of thrombotic thrombocytopenia induced by coronavirus disease 2019 (COVID-19) vaccines have been reported recently. Herein, we describe hemophagocytic lymphohistiocytosis (HLH) following COVID-19 vaccination. Case report: A 35-year-old male, chronic alcoholic, 3 years into abstinence received first dose Covishield vaccine. He started developing a fever, testicular pain, diminished sensorium requiring invasive ventilation, and decreased urine output 4 days after getting vaccinated. Initial workup for NCCT brain and HRCT chest was normal, tropical fever panel was negative, cultures for blood and endotracheal aspirate were sterile, liver and renal functions showed mild derangement, CSF study was normal. Ultrasound examination of the abdomen revealed mild hepatosplenomegaly, mild testicular swelling, and suprainguinal lymphadenopathy, with no focus of infection. Subsequently, he developed bicytopenia with haemoglobin 9.0 g/dL and platelet counts 50 × 109/L, ferritin 2130 μg/L, triglyceride 353 mg/dL, and decreased fibrinogen 1.41 g/L. Bone marrow as well as lymph node biopsy showed haemophagocytosis with engulfment of neutrophils, lymphocytes, and normoblasts making HLH a likely diagnosis. Soluble CD25 and NK cell function could not be performed. Extensive evaluation was done to look into the etiology of HLH. SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was negative. RT-PCR test for Epstein-Barr virus (EBV), influenza A (H1N1, H3N2), influenza B, cytomegalovirus (CMV) performed from endotracheal aspirate (ETA) was negative. Similarly, the RT-PCR test from serum samples for EBV, Parvo B-19, CMV, and from CSF sample for EBV, Parvo B-19, CMV, and HSV-1 was negative. Hepatitis B, C, and HIV serologies were negative. Culture and sensitivity repeated from blood, ETA and urine was sterile. Autoimmune panel including complements levels were negative. Peripheral smear, bone marrow, and lymph node biopsy were normal and did not reveal abnormal or malignant cells. He had persistent fevers to 38.6°C during the first 6 days of his admission, with a rise in his ferritin to 1950 μg/L. The patient received steroids but not etoposide. By the 8th day, his fevers resolved, with improvement in his lethargy and malaise. Two weeks later, his ferritin had reduced to 510 μg/L, platelet count rose to 180 × 109/L, and repeat ultrasound abdomen demonstrated resolution of his splenomegaly. In our patient, there was no clear precipitant of HLH other than the Covishield vaccine. There was no evidence of an infection or malignancy. Due to our patient's clinical stability, resolution of symptoms, and improvement of HLH parameters he did not require HLH specific therapy. It is unclear if he had a pre-existing genetic predisposition to HLH as genetic testing is pending, however, it is unlikely as he has reached the age of 35 and suffered from previous viral infections without developing HLH.

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.

Scrotal ultrasound in young men with acute scrotal pain: A retrospective consecutive case series audit

Introduction: Although not recommended by EAU guidelines, many men with acute scrotal pain undergo ultrasound (US) to screen for occult tumours. This has low diagnostic yield and must be weighed against the increased risks of coronavirus due to additional hospital attendances, inconvenience for the patient, and demand on NHS resources. We evaluated our case series to determine current practice and diagnostic yield. Method: 141 consecutive cases of scrotal pain and/or swelling were identified from our Trust's Surgical Assessment Unit (September- December 2020). Clinical diagnosis, and where performed, timing, indication and outcome of scrotal US was recorded. Results: 109/141 patients underwent scrotal US;the only urgent clinical indications were suspected collection/abscess (5 cases) or testicular mass (4). Relative indications included uncertain diagnosis (27 cases), suspected missed testicular torsion (6) and suspected hernia (1). 66/ 109 US performed were for 'soft' indications, however one occult testicular tumour, one acute testicular torsion and two inguinal herniae were unexpectedly found. Conclusions: Scrotal US changed immediate patient management in 1/ 109 cases (acute testicular torsion). Early outpatient US would be sufficient to diagnose occult testicular tumour, missed testicular torsions and groin herniae. There is too much reliance on US;more focus on history and examination is needed.

The effect of the COVID-19 pandemic on management of urological emergencies including risk of contracting COVID-19-a UK epicentre experience

Introduction & Objective: During the first wave of COVID-19 we saw a reduction in urgent urological admissions. Concurrently, we had to adapt and change our standard management of urological emergency admissions. We wished to evaluate the impact of COVID-19 on urological emergencies in a UK COVID-19 epicentre. Methods: Retrospective audit of all urological emergencies over a 10-week period (mid-March - end of May) in 2019 was compared to the same period during COVID-19. Results: From 2019 to 2020 we saw a reduction of 35% (187 [2019] and 122 [2020]) in urological emergency admissions. The average inpatient stay was 1.76 days (range 0-24 days) in 2020 from 2.65 days (range 0-38 days) in 2019. The largest reduction in presentation was seen in renal colic 43% (58 [2019] and 33 [2020]) followed by visible haematuria 39% (37 [2019] and 23 [2020]). There was a decrease in surgical management of urological emergencies during COVID-19. Scrotal exploration for testicular pain went from 57% (21 of 37) 2019 to 39% (12 of 31) during COVID-19. Stenting for colic and confirmed ureteric stones decreased from (20 of 25) 80% in 2019 to 11% (2 of 18) in 2020. “Hot” ESWL rates for ureteric stones increased from no patients [2019] to 61% (11 of 18) in 2020. In 2019, 12% (6 of 49) of emergency procedures were performed by Consultants however this increased to 48% (11 of 23) in 2020 due to redeployment of urological registrars. The overall in-hospital COVID-19 infection rate was only 0.82% during or within 28 days of discharge with no COVID-19 related mortality (0%). Conclusions: Inpatient infection rate from COVID-19 was very low and there was no related mortality therefore patients should not fear hospital attendance or admission. Longer term follow-up of patients managed conservatively rather than surgically is necessary to ensure no long-term harm has been caused by a change in standard surgical management of urological emergencies. (Table Presented).