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

October 11, 2023 updated by: Prof. Rosario Pivonello, Federico II University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Naples, Italy, 80131
        • Recruiting
        • Federico II University of Naples
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients of both sexes recovered from SARS-CoV-2 infection

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the most frequent phenotypes of Long-COVID syndrome among COVID-19 patients recently hospitalized and dismissed
Time Frame: Change from baseline at 3-12 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with andrological dysfunctions
Time Frame: Change from baseline at 3-12 months
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
Number of patients with reproductive dysfunctions
Time Frame: Change from baseline at 3-12 months
Prevalence of male reproductive dysfunctions: alterations of seminal parameters (oligo-, astheno-, teratozoospermia, azoospermia, necrozoospermia, leukocytospermia, hypo / hyperposia).
Change from baseline at 3-12 months
Number of patients with sexual dysfunctions
Time Frame: Change from baseline at 3-12 months
Prevalence of male sexual dysfunctions (erectile dysfunction, premature ejaculation, hypoactive sexual desire disorder).
Change from baseline at 3-12 months
Number of patients with olfactory dysfunctions
Time Frame: Change from baseline at 3-12 months
Prevalence of olfactory dysfunctions (hypo/anosmia and hypo/ageusia) in male and female patients.
Change from baseline at 3-12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Collaborators

Azienda Sanitaria Locale Napoli 2 Nord

Investigators

  • Principal Investigator: Rosario Pivonello, Prof., Federico II University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 27, 2022

Primary Completion (Estimated)

January 27, 2024

Study Completion (Estimated)

January 27, 2024

Study Registration Dates

First Submitted

May 16, 2022

First Submitted That Met QC Criteria

May 16, 2022

First Posted (Actual)

May 18, 2022

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LO-COCO-ANDRO

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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