Long Covid-19NCT05379556
LOng COvid COmorbidities: Andrological, Reproductive, Sexual Dysfunctions in Patients Recovered From COVID-19
An observational study of Long Covid-19, run by Federico II University at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long Covid-19
- What is being tested?
- Assessment of andrological profile of LO-COCO-ANDRO male patients, Assessment of reproductive function of LO-COCO-ANDRO male patients and Assessment of sexual function of LO-COCO-ANDRO male patients
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 27 Jan 2022to 27 Jan 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients of both sexes recovered from SARS-CoV-2 infection
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Federico II University of Naples
Naples, Italy, 80131
Rosario Pivonello, Prof., 3317328474, rosario.pivonello@unina.it
About this study
Official title: 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.
Read the 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.
- Conditions
- Long Covid-19
- Being tested
- Assessment of andrological profile of LO-COCO-ANDRO male patients, Assessment of reproductive function of LO-COCO-ANDRO male patients, Assessment of sexual function of LO-COCO-ANDRO male patients, Assessment of olfactory function of LO-COCO-ANDRO male and female patients
- Keywords
- Long Covid-19, Andrological complications, Reproductive complications, Sexual complications, Olfactory complications
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Assessment of andrological profile of LO-COCO-ANDRO male patientsDiagnostic test
Assessment of serum prolactin (PRL), luteininzing hormone (LH), follicle stimulating hormone (FSH), 17β-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 patientsDiagnostic test
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 patientsDiagnostic test
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 patientsDiagnostic test
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).
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline at 3-12 months
Secondary outcomes (4)
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).
Measured: Change from baseline at 3-12 months
Number of patients with reproductive dysfunctions
Prevalence of male reproductive dysfunctions: alterations of seminal parameters (oligo-, astheno-, teratozoospermia, azoospermia, necrozoospermia, leukocytospermia, hypo / hyperposia).
Measured: Change from baseline at 3-12 months
Number of patients with sexual dysfunctions
Prevalence of male sexual dysfunctions (erectile dysfunction, premature ejaculation, hypoactive sexual desire disorder).
Measured: Change from baseline at 3-12 months
Number of patients with olfactory dysfunctions
Prevalence of olfactory dysfunctions (hypo/anosmia and hypo/ageusia) in male and female patients.
Measured: Change from baseline at 3-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start27 Jan 2022
- Primary completion27 Jan 2026 (estimated)
- Study completion27 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Long Covid-19Studies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Sanitaria Locale Napoli 2 Nord
- Responsible party
- Principal investigator, Prof. Rosario Pivonello, Federico II University
- Investigators
- Rosario Pivonello, Prof., Principal investigator, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05379556
- Sponsor's protocol ID
- LO-COCO-ANDRO
- Status last verified
- Aug 2025
- First submitted
- 16 May 2022
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cardona Maya WD, Du Plessis SS, Velilla PA. SARS-CoV-2 and the testis: similarity with other viruses and routes of infection. Reprod Biomed Online. 2020 Jun;40(6):763-764. doi: 10.1016/j.rbmo.2020.04.009. Epub 2020 Apr 17.
PubMed 32362571Chen F, Lou D. Rising Concern on Damaged Testis of COVID-19 Patients. Urology. 2020 Aug;142:42. doi: 10.1016/j.urology.2020.04.069. Epub 2020 Apr 25. No abstract available.
PubMed 32343996Corona G, Baldi E, Isidori AM, Paoli D, Pallotti F, De Santis L, Francavilla F, La Vignera S, Selice R, Caponecchia L, Pivonello R, Ferlin A, Foresta C, Jannini EA, Lenzi A, Maggi M, Lombardo F. SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Societa Italiana di Andrologia e Medicina della Sessualita). J Endocrinol Invest. 2020 Aug;43(8):1153-1157. doi: 10.1007/s40618-020-01290-w. Epub 2020 May 27.
PubMed 32462316Douglas GC, O'Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI, Lew RA. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004 Oct;145(10):4703-11. doi: 10.1210/en.2004-0443. Epub 2004 Jul 1.
PubMed 15231706Illiano E, Trama F, Costantini E. Could COVID-19 have an impact on male fertility? Andrologia. 2020 Jul;52(6):e13654. doi: 10.1111/and.13654. Epub 2020 May 21.
PubMed 32436229Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA Netw Open. 2020 May 1;3(5):e208292. doi: 10.1001/jamanetworkopen.2020.8292.
PubMed 32379329Liu X, Chen Y, Tang W, Zhang L, Chen W, Yan Z, Yuan P, Yang M, Kong S, Yan L, Qiao J. Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes. Sci China Life Sci. 2020 Jul;63(7):1006-1015. doi: 10.1007/s11427-020-1705-0. Epub 2020 Apr 30.
PubMed 32361911Massarotti C, Garolla A, Maccarini E, Scaruffi P, Stigliani S, Anserini P, Foresta C. SARS-CoV-2 in the semen: Where does it come from? Andrology. 2021 Jan;9(1):39-41. doi: 10.1111/andr.12839. Epub 2020 Jul 28.
PubMed 32533891Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, Spivak AM, Alukal JP, Zhang X, Xiong C, Li PS, Hotaling JM. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020 Jun;113(6):1135-1139. doi: 10.1016/j.fertnstert.2020.04.024. Epub 2020 Apr 17.
PubMed 32482249Paoli D, Pallotti F, Colangelo S, Basilico F, Mazzuti L, Turriziani O, Antonelli G, Lenzi A, Lombardo F. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J Endocrinol Invest. 2020 Dec;43(12):1819-1822. doi: 10.1007/s40618-020-01261-1. Epub 2020 Apr 23.
PubMed 32329026Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells. 2020 Apr 9;9(4):920. doi: 10.3390/cells9040920.
PubMed 32283711Wenham C, Smith J, Morgan R; Gender and COVID-19 Working Group. COVID-19: the gendered impacts of the outbreak. Lancet. 2020 Mar 14;395(10227):846-848. doi: 10.1016/S0140-6736(20)30526-2. Epub 2020 Mar 6. No abstract available.
PubMed 32151325Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, Peh S, Gu J. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod. 2006 Feb;74(2):410-6. doi: 10.1095/biolreprod.105.044776. Epub 2005 Oct 19.
PubMed 16237152Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020 Sep;17(9):543-558. doi: 10.1038/s41569-020-0413-9. Epub 2020 Jul 20.
PubMed 32690910Sansone A, Mollaioli D, Ciocca G, Limoncin E, Colonnello E, Vena W, Jannini EA. Addressing male sexual and reproductive health in the wake of COVID-19 outbreak. J Endocrinol Invest. 2021 Feb;44(2):223-231. doi: 10.1007/s40618-020-01350-1. Epub 2020 Jul 13.
PubMed 32661947
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LOng COvid COmorbidities: Evaluation of Andrological, Reproductive and Sexual Functions in Patients Recovered From COVID-19
- ClinicalTrials.gov ID
- NCT05379556
- Acronym / sponsor ID
- LO-COCO-ANDRO
- Conditions
- Long Covid-19
- Keywords
- Long Covid-19, Andrological complications, Reproductive complications, Sexual complications, Olfactory complications
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Collaborators
- Azienda Sanitaria Locale Napoli 2 Nord
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- 27 Jan 2026 (estimated)
- Study completion
- 27 Jan 2027 (estimated)
- First posted
- 18 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients of both sexes recovered from SARS-CoV-2 infection
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Assessment of andrological profile of LO-COCO-ANDRO male patientsAssessment of serum prolactin (PRL), luteininzing hormone (LH), follicle stimulating hormone (FSH), 17β-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). | Diagnostic test | – |
| Assessment of reproductive function of LO-COCO-ANDRO male patientsSemen 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. | Diagnostic test | – |
| Assessment of sexual function of LO-COCO-ANDRO male patientsValidated 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. | Diagnostic test | – |
| Assessment of olfactory function of LO-COCO-ANDRO male and female patientsBrief 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). | Diagnostic test | – |
Primary outcome
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.
4 secondary outcomes
Number of patients with andrological dysfunctions
Time frame: Change from baseline at 3-12 months
Number of patients with reproductive dysfunctions
Time frame: Change from baseline at 3-12 months
Number of patients with sexual dysfunctions
Time frame: Change from baseline at 3-12 months
Number of patients with olfactory dysfunctions
Time frame: Change from baseline at 3-12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Background: PubMed 32362571Cardona Maya WD, Du Plessis SS, Velilla PA. SARS-CoV-2 and the testis: similarity with other viruses and routes of infection. Reprod Biomed Online. 2020 Jun;40(6):763-764. doi: 10.1016/j.rbmo.2020.04.009. Epub 2020 Apr 17.
- Background: PubMed 32343996Chen F, Lou D. Rising Concern on Damaged Testis of COVID-19 Patients. Urology. 2020 Aug;142:42. doi: 10.1016/j.urology.2020.04.069. Epub 2020 Apr 25. No abstract available.
- Background: PubMed 32462316Corona G, Baldi E, Isidori AM, Paoli D, Pallotti F, De Santis L, Francavilla F, La Vignera S, Selice R, Caponecchia L, Pivonello R, Ferlin A, Foresta C, Jannini EA, Lenzi A, Maggi M, Lombardo F. SARS-CoV-2 infection, male fertility and sperm cryopreservation: a position statement of the Italian Society of Andrology and Sexual Medicine (SIAMS) (Societa Italiana di Andrologia e Medicina della Sessualita). J Endocrinol Invest. 2020 Aug;43(8):1153-1157. doi: 10.1007/s40618-020-01290-w. Epub 2020 May 27.
- Background: PubMed 15231706Douglas GC, O'Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI, Lew RA. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004 Oct;145(10):4703-11. doi: 10.1210/en.2004-0443. Epub 2004 Jul 1.
- Background: PubMed 32436229Illiano E, Trama F, Costantini E. Could COVID-19 have an impact on male fertility? Andrologia. 2020 Jul;52(6):e13654. doi: 10.1111/and.13654. Epub 2020 May 21.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rosario Pivonello, Prof. principal investigator
Federico II University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Long Covid-19, run by Federico II University at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rosario Pivonello, Prof. (3317328474, rosario.pivonello@unina.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05379556, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.