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

NCT05379556 | Recruiting DMC

• 1 other identifier: LO-COCO-ANDRO
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Long Covid-19

Keywords

Long Covid-19; Andrological complications; Reproductive complications; Sexual complications; Olfactory complications

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of patients with andrological dysfunctions

  Change from baseline at 3-12 months

• Number of patients with reproductive dysfunctions

  Change from baseline at 3-12 months

• Number of patients with sexual dysfunctions

  Change from baseline at 3-12 months

• Number of patients with olfactory dysfunctions

  Change from baseline at 3-12 months

Interventions

Assessment of andrological profile of LO-COCO-ANDRO male patients DIAGNOSTIC_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 patients DIAGNOSTIC_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 patients DIAGNOSTIC_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 patients DIAGNOSTIC_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).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federico II University: lead
• Azienda Sanitaria Locale Napoli 2 Nord: collaborator

Study Sites (1)

Federico II University of Naples

Naples, Italy, 80131, Italy

RECRUITING

Related Publications (29)

• 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.

  PMID: 32362571 BACKGROUND

• Chen 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.

  PMID: 32343996 BACKGROUND

• Corona 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.

  PMID: 32462316 BACKGROUND

• Douglas 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.

  PMID: 15231706 BACKGROUND

• Illiano 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.

  PMID: 32436229 BACKGROUND

• Li 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.

  PMID: 32379329 BACKGROUND

• Liu 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.

  PMID: 32361911 BACKGROUND

• Massarotti 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.

  PMID: 32533891 BACKGROUND

• Pan 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.

  PMID: 32482249 BACKGROUND

• Paoli 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.

  PMID: 32329026 BACKGROUND

• Wang 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.

  PMID: 32283711 BACKGROUND

• Wenham 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.

  PMID: 32151325 BACKGROUND

• Xu 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.

  PMID: 16237152 BACKGROUND

• Nishiga 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.

  PMID: 32690910 BACKGROUND

• Sansone 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.

  PMID: 32661947 BACKGROUND

• Caretta N, De Rocco Ponce M, Minicuci N, Palego P, Valente U, Garolla A, Ferlin A, Foresta C. Penile doppler ultrasound predicts cardiovascular events in men with erectile dysfunction. Andrology. 2019 Jan;7(1):82-87. doi: 10.1111/andr.12561. Epub 2018 Nov 8.

  PMID: 30407754 BACKGROUND

• Varela CG, Yeguas LAM, Rodriguez IC, Vila MDD. Penile Doppler Ultrasound for Erectile Dysfunction: Technique and Interpretation. AJR Am J Roentgenol. 2020 May;214(5):1112-1121. doi: 10.2214/AJR.19.22141. Epub 2020 Jan 28.

  PMID: 31990215 BACKGROUND

• Sansone A, Mollaioli D, Ciocca G, Colonnello E, Limoncin E, Balercia G, Jannini EA. "Mask up to keep it up": Preliminary evidence of the association between erectile dysfunction and COVID-19. Andrology. 2021 Jul;9(4):1053-1059. doi: 10.1111/andr.13003. Epub 2021 Mar 30.

  PMID: 33742540 BACKGROUND

• Kloner RA. Erectile dysfunction as a predictor of cardiovascular disease. Int J Impot Res. 2008 Sep-Oct;20(5):460-5. doi: 10.1038/ijir.2008.20. Epub 2008 May 15.

  PMID: 18480824 BACKGROUND

• Corona G, Forti G, Maggi M. Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome. Aging Male. 2008 Dec;11(4):193-9. doi: 10.1080/13685530802468497.

  PMID: 19172551 BACKGROUND

• Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol. 2020 Aug 1;77(8):1018-1027. doi: 10.1001/jamaneurol.2020.2065.

  PMID: 32469387 BACKGROUND

• Hopkins C, Surda P, Kumar N. Presentation of new onset anosmia during the COVID-19 pandemic. Rhinology. 2020 Jun 1;58(3):295-298. doi: 10.4193/Rhin20.116.

  PMID: 32277751 BACKGROUND

• Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S. Features of anosmia in COVID-19. Med Mal Infect. 2020 Aug;50(5):436-439. doi: 10.1016/j.medmal.2020.04.006. Epub 2020 Apr 17.

  PMID: 32305563 BACKGROUND

• Tong JY, Wong A, Zhu D, Fastenberg JH, Tham T. The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2020 Jul;163(1):3-11. doi: 10.1177/0194599820926473. Epub 2020 May 5.

  PMID: 32369429 BACKGROUND

• Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL, Calvo-Henriquez C, Lavigne P, Falanga C, Barillari MR, Cammaroto G, Khalife M, Leich P, Souchay C, Rossi C, Journe F, Hsieh J, Edjlali M, Carlier R, Ris L, Lovato A, De Filippis C, Coppee F, Fakhry N, Ayad T, Saussez S. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261. doi: 10.1007/s00405-020-05965-1. Epub 2020 Apr 6.

  PMID: 32253535 BACKGROUND

• Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020 Apr 1;11(7):995-998. doi: 10.1021/acschemneuro.0c00122. Epub 2020 Mar 13.

  PMID: 32167747 BACKGROUND

• Deems DA, Doty RL, Settle RG, Moore-Gillon V, Shaman P, Mester AF, Kimmelman CP, Brightman VJ, Snow JB Jr. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg. 1991 May;117(5):519-28. doi: 10.1001/archotol.1991.01870170065015.

  PMID: 2021470 BACKGROUND

• Pence TS, Reiter ER, DiNardo LJ, Costanzo RM. Risk factors for hazardous events in olfactory-impaired patients. JAMA Otolaryngol Head Neck Surg. 2014 Oct;140(10):951-5. doi: 10.1001/jamaoto.2014.1675.

  PMID: 25170573 BACKGROUND

• Meng X, Deng Y, Dai Z, Meng Z. COVID-19 and anosmia: A review based on up-to-date knowledge. Am J Otolaryngol. 2020 Sep-Oct;41(5):102581. doi: 10.1016/j.amjoto.2020.102581. Epub 2020 Jun 2.

  PMID: 32563019 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rosario Pivonello, Prof.

  Federico II University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rosario Pivonello, Prof.

CONTACT

3317328474; rosario.pivonello@unina.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 18, 2022
• Study Start: January 27, 2022
• Primary Completion: January 27, 2026
• Study Completion (Estimated): January 27, 2027
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)