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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Long Covid-19

Intervention / Treatment
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* Diagnostic Test: Assessments of endocrinological phenotypes of LO-COCO patients
* Diagnostic Test: Assessment of muscular phenotypes of LO-COCO patients
* Diagnostic Test: Assessment of neuropsychiatric phenotypes of LO-COCO patients
* Procedure: Muscle biopsy
* Diagnostic Test: Assessment of pulmonary phenotypes of LO-COCO patients
* Diagnostic Test: Assessment of cardiological phenotypes of LO-COCO patients
* Diagnostic Test: Assessment of vascular phenotypes of LO-COCO patients
* Diagnostic Test: Assessment of dermatological phenotypes of LO-COCO patients
* Procedure: Tissue biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|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).|
|Diagnostic Test: 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.|
|Diagnostic Test: 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.|
|Diagnostic Test: 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)|
|Diagnostic Test: 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.|
|Diagnostic Test: 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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thyroid dysfunctions | Prevalence of thyroid dysfunctions (hypo, hyper functions; thyroiditis) | Change from baseline at 3-12 months | 
| Female gonadal dysfunctions | Prevalence of female gonadal dysfunctions (hypogonadism and female sexual dysfunctions) | Change from baseline at 3-12 months | 
| Adrenal dysfunctions | Prevalence of adrenal dysfunctions (hypocortisolism) | Change from baseline at 3-12 months | 
| Pituitary dysfunctions | Prevalence of pituitary dysfunctions (hyperprolactinemia, GH deficiency) | Change from baseline at 3-12 months | 
| 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 | 
| 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 | 
| Muscle dysfunctions | Prevalence of fatigue, reduced resistance and muscle strength, reduced muscle power, reduced exercise tolerance, myopathy. | Change from baseline at 3-12 months | 
| 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 | 
| Cardiological dysfunctions | Prevalence of echocardiographic changes at rest and during echocardiogram stress tests, dysfunctions in cardiopulmonary performance | Change from baseline at 3-12 months | 
| Post-thrombotic vascular dysfunctions | Prevalence of previously unknown deep venous thrombosis | Change from baseline at 3-12 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long Covid-19, Endocrine Complications, Metabolic Complications, Neuropsychiatric Complications, Muscular Complications, Cardiovascular Complications, Pulmonary Complications, Dermatologic Complications