LOng COvid COmorbidities: Andrological, Reproductive, Sexual Dysfunctions in Patients Recovered From COVID-19

Long Covid-19 Clinical Trial

Official title:

LOng COvid COmorbidities: Evaluation of Andrological, Reproductive and Sexual Functions in Patients Recovered From COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05379556
• Other study ID #: LO-COCO-ANDRO
• Status: Recruiting
• Start date: January 27, 2022
• Est. completion date: January 27, 2024

Study information

• Verified date: October 2023
• Source: Federico II University
• Contact: Rosario Pivonello, Prof.
• Phone: 3317328474
• Email: rosario.pivonello[@]unina.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Considering the compelling amount of studies focused on patients in the active phase of COVID-19 disease and the scarcity of studies focused on patient cured from disease aimed at evaluating the sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the purpose of the study is to investigate, in patients recovered from COVID-19 disease: 1) whether SARS-CoV-2 infection has induced in male patients, a primary (testicular) and / or secondary (pituitary) damage to the hypothalamic-pituitary-testicular hormonal axis, structural and / or functional damage to the testis and penis, sexual dysfunction or fertility disorders; 2) the prevalence in male and female patients of chemosensory symptoms (olfactory dysfunction) and assess whether there is a correlation between the prevalence, severity, duration and eventual persistence of olfactory dysfunction and the severity of COVID-19 disease. Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months. A better definition of the prevalence and type of sequelae after recovery from COVID-19 disease could significantly improve the therapeutic management and long-term follow-up of these patients, with a relevant impact in terms of health resources and public health.

Description:

The testis is among the male organs with the highest expression of angiotensin-converting enzyme 2 (ACE2), particularly in Sertoli cells, Leydig cells, spermatogonia, spermatocytes and spermatids; therefore, the possibility of SARS-CoV-2 infection spread to the testis and of a direct damage to testicular endocrine function and spermatogenesis is not a negligible aspect. In addition, the possibility of indirect testicular damage has been suggested; indeed, orchitis has been reported in patients with SARS-CoV-2, favored by the activation of a systemic inflammatory response to SARS-CoV-2 infection, and changes in gonadotropin levels that support the presence of subclinical or compensated hypogonadism associated with SARS-CoV-2 infection have been highlighted, although the possibility of effects mediated by the inflammatory state, the use of corticosteroids or stress cannot be excluded. Controversial data are available regarding the possibility that SARS-CoV-2 infection can actually spread to semen, and there is currently no evidence of a direct association between SARS-CoV-2 infection and male infertility, although an altered expression of ACE2 has been associated with non-obstructive azoospermia. The widespread expression of ACE2 by endothelial cells represents an additional susceptibility alert in relation to the male reproductive system, as well as to sexual function, in particular for the potential direct and indirect effects of SARS-CoV-2 infection on the penile vascular endothelium; indeed, multiple evidences support the presence of a multi-organ endothelial dysfunction in SARS-CoV-2 infection, connected to the direct tropism of the virus mediated by the diffuse expression of ACE-2 in endothelial cells, as well as to the systemic inflammation through the increased production of pro-inflammatory cytokines which mediate/favor the alteration of the function and permeability of the vascular endothelium. In this context, erectile dysfunction could represent a long-term complication of Covid-19; penile vascular endothelial dysfunction is indeed recognized as the dominant mechanism in the onset of vasculogenic erectile dysfunction, and preliminary studies highlight a significantly higher prevalence of erectile dysfunction in patients with Covid-19, regardless of other variables affecting erectile function, such as psychological state, age and body mass index. Anosmia/hyposmia, associated or not with ageusia, has been frequently reported as a symptom of the onset of SARS-CoV-2 infection, but it could also remain the only clinical manifestation in some paucisymptomatic patients. The incidence of anosmia in SARS-CoV-2 patients is around values between 33.9% and 68%, with a predominance in the female sex. The etiopathogenetic mechanisms underlying the onset of anosmia in these patients are yet to be fully clarified; the main mechanisms proposed include damage to olfactory sensory neurons or direct invasion of the brain via the olfactory bulb. Smell disorders affect nutrition and quality of life with important psycho-social consequences. In this scenario, it appears of primary importance to evaluate and monitor the long-term evolution of anosmia in post SARS-CoV-2 infection through an objective assessment.

The aim of the study is to investigate whether in male patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced: 1) alterations of seminal parameters (oligo-, astheno-, teratozoospermia, azoospermia, necrozoospermia, leukocytospermia, hypo / hyperposia); 2) hypogonadism; 3) morpho-structural alterations of the testis evaluated by ultrasonography (testicular hypotrophy, testicular and / or epididymal inhomogeneity, testicular calcifications / microlithiasis, testicular solid lesions, hydrocele, varicocele, altered testicular and / or epididymal vascularization); 4) prostate-vesicular morpho-structural alterations assessed by ultrasonography; 5) morpho-structural and hemodynamic alterations of the penis evaluated by ultrasonography with Color and PowerDoppler performed at baseline, and in some selected cases which will be identified as pathological at baseline, also performed dynamically after intra-cavernous infiltration of prostaglandin-E1 (PGE1) (morphological alterations, nodules, alterations of the albuginea tunic, presence of fibrotic or calcified plaques, morphological and haemodynamic alterations of the cavernous arteries, anastomosis between the cavernous arteries and the dorsal artery, presence of other collateral circulation, presence and site of any occlusions); 6)male sexual dysfunctions (erectile dysfunction, premature ejaculation, hypoactive sexual desire disorder) assessed by sexological questionnaires. Moreover, the aim of the study is also to investigate whether in male and female patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced an olfactory dysfunction, with evaluation of the eventual correlation between prevalence, severity, duration and possible permanence of olfactory dysfunction and the severity of the COVID-19 disease, using the Sniffin 'Sticks test for the evaluation of: odor threshold (T), odor discrimination (D) and odor identification (I) (TDI score).

Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 27, 2024
• Est. primary completion date: January 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients of both sexes recovered from SARS-CoV-2 infection (two negative nasopharyngeal swabs, negative IgM and positive anti SARS-CoV-2 IgG);

• Aged over 18 years of age;

• Ability to understand protocol procedures

Exclusion Criteria:

• Any psychological/psychiatric/other medical conditions compromising the understanding of the nature and purpose of the study, and of its possible consequences

• Uncooperative attitude of the patient

Related Conditions & MeSH terms

• COVID-19
• Long Covid-19

Intervention

Diagnostic Test:
• Assessment of andrological profile of LO-COCO-ANDRO male patients
Assessment of serum prolactin (PRL), luteininzing hormone (LH), follicle stimulating hormone (FSH), 17ß-estradiol, testosterone. Physical examination with measurement of body weight, height, body mass index, waist and hip circumference. Andrological physical examination with evaluation of testis volume with Prader orchidometer, testicular consistency and lesions, varicocele. Scrotal ultrasound performed in longitudinal, transverse and oblique scans using a high frequency linear probe with grayscale and color-doppler; transrectal prostate ultrasound performed with transverse, longitudinal and oblique scans using an "end fire" probe; basal penile ultrasound will be performed in longitudinal and transverse scans using a high frequency linear probe with grayscale and color-doppler; dynamic penile ultrasound performed as described for basal penile ultrasound after intra-cavernous infiltration of 10 mcg of prostaglandin-E1 (PGE1).
• Assessment of reproductive function of LO-COCO-ANDRO male patients
Semen samples will be collected on site by masturbation directly into a sterile plastic container after 3-5 days of sexual abstinence. The sample will be analyzed according to World Health Organization (WHO) 2010 guidelines. Semen samples will be stored for biochemical and molecular evaluations.
• Assessment of sexual function of LO-COCO-ANDRO male patients
Validated questionnaires to assess the prevalence of male sexual disorders, namely erectile dysfunction with International Index of Erectile function 15 (IIEF-15), premature ejaculation with premature ejaculation diagnostic tool (PEDT), hypoactive sexual desire disorder with andrological structured interview on erectile dysfunction (ANDRO-SIEDY). Patients will be also interviewed to evaluate lifestyle habits.
• Assessment of olfactory function of LO-COCO-ANDRO male and female patients
Brief interview to collect patient's anamnesis relative to olfactory function, with particular reference to hypo / anosmia and hypo/ageusia onset timeline, duration and regression. Interview for the self-assessment of chemosensory skills and for the evaluation of quality of life in relation to olfactory dysfunction. Sniffin 'Sticks test for the evaluation of odor threshold (T), odor discrimination (D) and odor identification (I) (TDI score).

Locations

Country	Name	City	State
Italy	Federico II University of Naples	Naples

Sponsors (2)

Lead Sponsor	Collaborator
Federico II University	Azienda Sanitaria Locale Napoli 2 Nord

Country where clinical trial is conducted

Italy, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of the most frequent phenotypes of Long-COVID syndrome among COVID-19 patients recently hospitalized and dismissed	This pilot study will allow identifying the frequency and type of andrological, reproductive, sexual and olfactory disorders that contribute to the long covid syndrome.	Change from baseline at 3-12 months
Secondary	Number of patients with andrological dysfunctions	Prevalence of andrological dysfunctions (hypogonadism, morpho-structural alterations of the testis including testicular hypotrophy, testicular and / or epididymal inhomogeneity, testicular calcifications / microlithiasis, testicular solid lesions, hydrocele, varicocele, altered testicular and / or epididymal vascularization, prostate-vesicular morpho-structural alterations, morpho-structural and hemodynamic alterations of the penis including nodules, alterations of the albuginea tunic, presence of fibrotic or calcified plaques, morphological and haemodynamic alterations of the cavernous arteries, anastomosis between the cavernous arteries and the dorsal artery, collateral circulation, occlusions).	Change from baseline at 3-12 months
Secondary	Number of patients with reproductive dysfunctions	Prevalence of male reproductive dysfunctions: alterations of seminal parameters (oligo-, astheno-, teratozoospermia, azoospermia, necrozoospermia, leukocytospermia, hypo / hyperposia).	Change from baseline at 3-12 months
Secondary	Number of patients with sexual dysfunctions	Prevalence of male sexual dysfunctions (erectile dysfunction, premature ejaculation, hypoactive sexual desire disorder).	Change from baseline at 3-12 months
Secondary	Number of patients with olfactory dysfunctions	Prevalence of olfactory dysfunctions (hypo/anosmia and hypo/ageusia) in male and female patients.	Change from baseline at 3-12 months