LOng COvid COmorbidities: Endocrine,Metabolic,Neuropsychiatric,Muscle,Cardiovascular,Pulmonary,Dermatologic Dysfunctions

Long Covid-19 Clinical Trial

— LO-COCO  

Official title:

LOng COvid COmorbidities: Evaluation of Endocrine, Metabolic, Neuropsychiatric, Muscle, Cardiovascular, Pulmonary and Dermatologic Functions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05293366
• Other study ID #: LO-COCO
• Status: Recruiting
• Start date: January 27, 2022
• Est. completion date: January 27, 2024

Study information

• Verified date: March 2022
• Source: Federico II University
• Contact: Annamaria Colao, Prof
• Phone: 3285390000
• Email: colao[@]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 SARS-CoV-2 infection, the purpose of the study is to investigate whether in patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced: 1) endocrine-metabolic function damage; 2) neuro-psychiatric damage; 3) muscle damage; 4) pulmonary damage; 5) cardiological damage; 6) venous vascular damage; 7) dermatological damage. 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 aim of the study is to investigate whether in patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced: 1) Endocrine-metabolic function damage, 2) Neuro-psychiatric damage, 3) Muscle damage, 4) Pulmonary damage, 5) Cardiological damage, 6) Post-thrombotic vascular damage, 7) Dermatological damage.

The assessment of the potential endocrine-metabolic function damage will comprise the investigation of alterations in particular in: thyrotropic axis (prevalence of hypothyroidism and alterations of the thyroid gland); female gonadotropic axis (prevalence of hypogonadism) with assessment of potentially impaired reproductive and sexual function (prevalence of morpho-structural alterations of the ovary, sexual dysfunction); corticotropic axis (prevalence of hypoadrenalism and alterations of the adrenal gland); somatotropic axis (prevalence of growth hormone deficiency); lactotropic axis (prevalence of hyperprolactinaemia); metabolic profile (prevalence of metabolic syndrome, overweight, obesity, insulin resistance, type 2 diabetes mellitus, dyslipidemia, hypovitaminosis D).

The assessment of the potential neuro-psychiatric damage will comprise the investigation of prevalence of depression, alteration in the quality of life, apathy, anxiety, deficit of attention and cognitive skills.

The assessment of the potential muscle damage will comprise the investigation of prevalence of fatigue, reduced resistance and muscle strength, reduced muscle power, reduced exercise tolerance, myopathy.

The assessment of the potential pulmonary damage will comprise the investigation of prevalence of parenchymal sequelae of interstitial/organized pneumonia, lung dysfunctions, dyspnoea.

The assessment of the potential cardiological damage will comprise the investigation of prevalence of echocardiographic changes at rest and during echocardiogram stress tests, dysfunctions in cardiopulmonary performance.

The assessment of the potential post-thrombotic vascular damage will comprise the investigation of prevalence of previously unknown deep venous thrombosis.

The assessment of the potential dermatological damage will comprise the investigation of prevalence of cutaneous and mucosal lesions, defluvium with identification of specific trichoscopic patterns and onychopathies with identification of specific onychoscopic/capillaroscopic patterns.

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:
• Assessments of endocrinological phenotypes of LO-COCO patients
Assessment of:thyroid-stimulating hormone(TSH),free triiodothyronine (FT3), free thyroxine (FT4),calcitonin,antibodies against thyroglobulin (AbTG) and against thyroperoxidase (AbTPO),adrenocorticotropic hormone (ACTH),cortisol, luteinizing hormone (LH),follicle-stimulating hormone(FSH),Testosterone,17-beta estradiol,sex hormone binding globulin (SHBG),progesterone, prolactin (PRL), growth hormone (GH), insulin growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS),delta 4-androstenedione,aldosterone,renin,glycemia, insulinemia, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, HbA1c, vitamin D, adiponectin, irisin, IL-6.Thyroid and ovarian ultrasounds, pituitary and adrenal MRI will be performed as well. Body composition will be assessed with bioimpedance analysis and DXA scans.Female sexual dysfunctions will be evaluated with Female Sexual Function Index (FSFI), Sexual Inhibition and Sexual Excitation Scale (SIS/SES),Body Uneasiness Test (BUT).
• Assessment of muscular phenotypes of LO-COCO patients
Questions will be collected regarding the tolerance to physical activity and modifications after diagnosis of Covid. Muscular strength will be assessed by means of tests (Medical Research Council Scale) and dynamometers. Balance will be assessed with a Romberg test, tolerance to stress will be assessed by means of cyclometer.
• Assessment of neuropsychiatric phenotypes of LO-COCO patients
Validated questionnaires will be collected to investigate depression (Beck Depression Inventory-II, BDI-II), apathy (Apathy Evaluation Scale, AES), anxiety (Test Anxiety Inventory, TAI), attention and cognitive functions (Montreal Cognitive Assessment and Quick Mild Cognitive Impairment). Fatigue will be assessed by Fatigue Rating Scale (FRS) and Fatigue Severity Scale (FSS). Muscle power will be assessed by six-minute walking test and sit and stand up test. The presence of myopathy will be evaluated by mean electrophysiological study.

Procedure:
• Muscle biopsy
Muscle biopsy will be performed upon need.

Diagnostic Test:
• Assessment of pulmonary phenotypes of LO-COCO patients
Modified Medical Research council questionnaire will be administered for evaluating of the dyspnoea level. Complete respiratory status assessment, including global spirometry, CO lung diffusion capacity and arterial gases analysis will be run. HRCT - high resolution CT scan of the chest - will be performed in selected cases to rule out the eventual sequelae of SARS-Cov2 related pneumonia.
• Assessment of cardiological phenotypes of LO-COCO patients
Cardiological assessment will be run upon data collected from: Short Form-36 Health Survey (SF36), echocardiogram at rest and during stress tests, six-minute walking test, N-terminal fragment brain natriuretic peptides (NT-proBNP)
• Assessment of vascular phenotypes of LO-COCO patients
The assessment of the potential post-thrombotic vascular damage will comprise the investigation of prevalence of previously unknown deep venous thrombosis by ultrasonography.
• Assessment of dermatological phenotypes of LO-COCO patients
Dermatology evaluation will account on: thrichoscopy, dermoscopy, onychoscopy and capillaroscopy, confocal microscopy, skin ultrasonography

Procedure:
• Tissue biopsy
Tissue biopsy will be performed upon need.

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 (13)

Agarwal S, Agarwal SK. Endocrine changes in SARS-CoV-2 patients and lessons from SARS-CoV. Postgrad Med J. 2020 Jul;96(1137):412-416. doi: 10.1136/postgradmedj-2020-137934. Epub 2020 Jun 11. Review. — View Citation

Auriemma RS, Pirchio R, Liccardi A, Scairati R, Del Vecchio G, Pivonello R, Colao A. Metabolic syndrome in the era of COVID-19 outbreak: impact of lockdown on cardiometabolic health. J Endocrinol Invest. 2021 Dec;44(12):2845-2847. doi: 10.1007/s40618-021-01563-y. Epub 2021 May 26. — View Citation

Bellastella G, Maiorino MI, Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands? J Endocrinol Invest. 2020 Aug;43(8):1169-1170. doi: 10.1007/s40618-020-01311-8. Epub 2020 Jun 1. — View Citation

Carfì A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603. — View Citation

D'Alto M, Marra AM, Severino S, Salzano A, Romeo E, De Rosa R, Stagnaro FM, Pagnano G, Verde R, Murino P, Farro A, Ciccarelli G, Vargas M, Fiorentino G, Servillo G, Gentile I, Corcione A, Cittadini A, Naeije R, Golino P. Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS. Crit Care. 2020 Nov 30;24(1):670. doi: 10.1186/s13054-020-03385-5. — View Citation

Evans PC, Rainger GE, Mason JC, Guzik TJ, Osto E, Stamataki Z, Neil D, Hoefer IE, Fragiadaki M, Waltenberger J, Weber C, Bochaton-Piallat ML, Bäck M. Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc Res. 2020 Dec 1;116(14):2177-2184. doi: 10.1093/cvr/cvaa230. Review. — View Citation

Fabbrocini G, Vastarella M, Nappa P, Annunziata MC, Camela E, Greco V, Gaudiello F, Alessio M, Pierri L, Catzola A, Guarino A. A new dermoscopic pattern for chilblain-COVID-19-like skin lesions in adolescents. JAAD Case Rep. 2020 Dec;6(12):1271-1274. doi: 10.1016/j.jdcr.2020.09.024. Epub 2020 Oct 1. — View Citation

Isidori AM, Arnaldi G, Boscaro M, Falorni A, Giordano C, Giordano R, Pivonello R, Pofi R, Hasenmajer V, Venneri MA, Sbardella E, Simeoli C, Scaroni C, Lenzi A. COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency. J Endocrinol Invest. 2020 Aug;43(8):1141-1147. doi: 10.1007/s40618-020-01266-w. Epub 2020 Apr 25. Review. — View Citation

Muscogiuri G, Barrea L, Savastano S, Colao A. Nutritional recommendations for CoVID-19 quarantine. Eur J Clin Nutr. 2020 Jun;74(6):850-851. doi: 10.1038/s41430-020-0635-2. Epub 2020 Apr 14. Review. — View Citation

Muscogiuri G, Pugliese G, Barrea L, Savastano S, Colao A. Commentary: Obesity: The "Achilles heel" for COVID-19? Metabolism. 2020 Jul;108:154251. doi: 10.1016/j.metabol.2020.154251. Epub 2020 Apr 27. — View Citation

Ocampo-Garza SS, Vastarella M, Nappa P, Cantelli M, Fabbrocini G. Telogen effluvium in the new SARS-CoV-2 era. Int J Dermatol. 2021 Jul;60(7):e265-e266. doi: 10.1111/ijd.15482. Epub 2021 Mar 4. — View Citation

Ortelli P, Ferrazzoli D, Sebastianelli L, Engl M, Romanello R, Nardone R, Bonini I, Koch G, Saltuari L, Quartarone A, Oliviero A, Kofler M, Versace V. Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom. J Neurol Sci. 2021 Jan 15;420:117271. doi: 10.1016/j.jns.2020.117271. Epub 2020 Dec 14. — View Citation

Pivonello R, Auriemma RS, Pivonello C, Isidori AM, Corona G, Colao A, Millar RP. Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger? Neuroendocrinology. 2021;111(11):1066-1085. doi: 10.1159/000513346. Epub 2020 Nov 26. Review. — View Citation

* Note: There are 13 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 for COVID-19 patients recently hospitalized and dismissed	This pilot study will allow identifying the frequency and type of endocrinologic, muscular, cardiovascular, pulmonary, dermatological, metabolic and neuropsychiatric disorders that contribute to the long covid syndrome .	Change from baseline at 3-12 months
Secondary	Thyroid dysfunctions	Prevalence of thyroid dysfunctions (hypo, hyper functions; thyroiditis)	Change from baseline at 3-12 months
Secondary	Female gonadal dysfunctions	Prevalence of female gonadal dysfunctions (hypogonadism and female sexual dysfunctions)	Change from baseline at 3-12 months
Secondary	Adrenal dysfunctions	Prevalence of adrenal dysfunctions (hypocortisolism)	Change from baseline at 3-12 months
Secondary	Pituitary dysfunctions	Prevalence of pituitary dysfunctions (hyperprolactinemia, GH deficiency)	Change from baseline at 3-12 months
Secondary	Metabolic dysfunctions	Prevalence of metabolic dysfunctions (metabolic syndrome, type 2 diabetes, overweight, obesity, insulin-resistance, dyslipidemia, hypovitaminosis D)	Change from baseline at 3-12 months
Secondary	Neuro-psychiatric dysfunctions	Prevalence of depression, alteration of the quality of life, apathy, anxiety, deficit of attentional and cognitive skills	Change from baseline at 3-12 months
Secondary	Muscle dysfunctions	Prevalence of fatigue, reduced resistance and muscle strength, reduced muscle power, reduced exercise tolerance, myopathy.	Change from baseline at 3-12 months
Secondary	Pulmonary dysfunctions	Prevalence of persisting respiratory discomfort in relation to lung function and radiological outcomes (interstitial/organized pneumonia, pulmonary fibrosis)	Change from baseline at 3-12 months
Secondary	Cardiological dysfunctions	Prevalence of echocardiographic changes at rest and during echocardiogram stress tests, dysfunctions in cardiopulmonary performance	Change from baseline at 3-12 months
Secondary	Post-thrombotic vascular dysfunctions	Prevalence of previously unknown deep venous thrombosis	Change from baseline at 3-12 months
Secondary	Dermatological dysfunctions	Prevalence of cutaneous and mucosal lesions, defluvium with identification of specific trichoscopic patterns and onychopathies with identification of specific onychoscopic/capillaroscopic patterns.	Change from baseline at 3-12 months