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Peyronie's disease in a patient after COVID‐19 infection: A case report

Abstract Coronavirus disease 2019 (COVID‐19) is an emerging infectious disease caused by a novel coronavirus (SARS‐CoV‐2), which demonstrates the ability to invade endothelial cells and cause systemic inflammation. Many possible long‐term sequelae of COVID‐19 remain unidentified. We describe a case of a man who developed Peyronie's disease after a resolved COVID‐19 infection. Erectile dysfunction was confirmed by the International Index of Erectile Function‐15(IIEF) and Sexual Health Inventory for Men(SHIM) scores. A diagnosis was Peyronie's disease was confirmed on ultrasound. Furthermore, he was found to have low endothelial progenitor cells colony‐forming units and low brachial artery flow‐mediated vasodilation, both of that are indicative of endothelial dysfunction. This case suggests Peyronie's disease should be considered as a possible sequela of COVID‐19 infection and providers should inquire about a history of COVID‐19 infection in patients presenting with Peyronie's disease.


| TRE ATMENT AND E VALUATI ON
The patient was prescribed tadalafil 5-mg PO daily for painful erections. Penile duplex was conducted with a 0.05-cc intracavernosal injection of alprostadil, papaverine, and phentolamine (Trimix) to achieve 100% rigidity. A curvature of 40 degrees dorsal and 30 degrees to the left was noticed. Calcified plaques measuring 0.5 × 0.5 cm and 1.0 × 1.5 cm were seen on ultrasound (US). Normal systolic velocities (right = 33.6 cm/s, left = 31.4 cm/s), slightly elevated end-diastolic velocities (right = 5.76 cm/s, left = 5.76 cm/s), and possible venous leak were noted at 10 min ( Figure 1). International index of erectile function-15 (IIEF-15) scores of 3, 1, 7, 0, and 2 were reported in corresponding domains indicating erectile dysfunction, orgasmic dysfunction, normal sexual desire, intercourse dissatisfaction, and overall dissatisfaction. Additionally, he scored 20 on the SHIM, indicating mild erectile dysfunction.
Endothelial progenitor cells (EPCs) are a unique type of stem cell, which is involved with the repair of vascular endothelium throughout the body. Patients with higher levels of circulating EPCs are thought to have higher capacity for cardiovascular self-regeneration.
EPCs can be tested by collecting a blood sample and growing the cells in culture according to an established 5-day standard protocol, generating a quantifiable amount of EPC-colon forming units (EPC-CFUs) (Hill et al., 2003). Brachial artery flow-mediated vasodilation (FMD) is another measure of systemic endothelial function, which utilises ultrasound to assess changes in brachial artery diameter after blood pressure cuff arterial occlusion (Corretti et al., 2002).
Patients with FMD values less than 7% are considered to have endothelial dysfunction. EPCs and FMD were compared against a positive and negative control group to contextualise the endothelial function results. Negative control group ('No PD') contained 27 patients with cardiovascular disease (such as diabetes or cardiomyopathy) and had IIEF scores >24 (indicative of normal erectile function). Positive control group consisted of nine healthy controls who had no significant medical history. This patient's EPC-CFUs were zero. Additionally, his FMD was impaired at 2.35% (normal value >7%) (Table 2, Figure 2).

| CON CLUS IONS
This case represents a patient with confirmed Peyronie's disease after the resolution of COVID-19 infection. His IIEF and SHIM scores were both indicative of erectile dysfunction. His low EPC and FMD% are suggestive of endothelial dysfunction. To our knowledge, this is the first case of Peyronie's disease reported after COVID-19 infection. Peyronie's disease should be considered as a possible sequela of COVID-19 infection due to widespread endothelial dysfunction.

| D ISCUSS I ON
COVID-19 is often considered to be a vascular disease due to the prothrombotic state it produces in many patients; the mechanism behind this involves direct endothelial invasion, which decreases the antithrombic activity of the normal epithelium (Bonaventura et al., 2021). Cell cultures demonstrate that SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) receptor for cell entry and transmembrane protease serine 2 (TMPRSS2) receptor for viral spike TA B L E 1 Lab results completed 29 days after resolution of COVID-19 infection brought in by patient upon initial presentation to urology clinic  There is evidence of affiliated androgen deficiency in the context of COVID-19. A prospective cohort study consisting of 262 men examined three different groups: 89 hospitalised men with COVID-19 (group 1), 30 hospitalised men with non-COVID-19 respiratory tract infection (group 2), and 143 age-matched controls admitted to urology outpatient clinic for reproductive function evaluation (group 3) (Kadihasanoglu et al., 2021). This study found a median testosterone level of 185.52 ng/dl in group 1, which was significantly less than group 2 (288.67 ng/dl) and group 3 (332 ng/dl). The prevalence of testosterone deficiency in group 1 was 74.3%, which was significantly greater than group 2 at 53.3% and group 3 at 37.8%. Furthermore, median serum luteinizing hormone (LH) and prolactin (PRL) levels were significantly higher in group 1 and 2 (group 1: LH = 5.67 U/L, PRL = 9.6 μg/L, group 2: LH = 5.39 U/L, PRL = 9.61 μg/L) when compared to group 3 (LH = 4.1 U/L, PRL = 7.5 μg/L), but there was no significant difference between group 1 and 2. The increase in LH is an expected outcome of compensated hypogonadism and elevated LH is triggered by increased interleukin (specifically 1, 2, and 6) levels.
In addition to testicular inflammation and hypogonadism, it has been proposed that COVID-19 may cause erectile dysfunction due to the endothelial invasion demonstrated by SARS-CoV-2  infection (Kresch et al., 2021). Taken together, these studies indicate that COVID-19 likely affects the reproductive system of many patients and further studies should evaluate the long-and short-term effects of COVID-19 infection on sexual function and fertility.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.