HSD3B1 Gene Polymorphisms With Outcomes in SARS-CoV-2 Infected Patients

Study Overview
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Brief Summary
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The study includes 2 sub-projects. Sub-project 1: The aim is to evaluate the expression of receptors and activating proteases mediating SARS-CoV-2 entry and spreading in the local population of Ticino. Sub-project 2: The aim is to investigate the association between the HSD3B1 gene variations and outcome of COVID-19 in the local population of Ticino.

Detailed Description
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Sub-project 1: This is an observational retrospective study that aims to evaluate the expression of receptors and activating proteases mediating SARS-CoV-2 entry and spreading in the local population of Ticino. The level of expression of these factors will be compared between infected and non-infected subjects. The sub-project will examine RNA samples from nasopharyngeal swabs taken from subjects tested for COVID-19. Sub-project 2: This is a haplotype- and diplotype-based case-control retrospective study that aims to investigate the association between the HSD3B1 gene variations and outcome of COVID-19 in the local population of Ticino. The gene status of HSD3B1 will be defined and compared between two groups of patients: the patients who experienced a severe SARS-CoV-2 infection (severe pulmonary insufficiency, ICU admission, eventually death) and the group with a mild-moderate COVID-19 disease without pulmonary insufficiency and oxygen need.

Official Title
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An Exploratory Analysis of the Expression of Receptors and Activating Proteases Mediating SARS-CoV-2 Entry and the Association Between HSD3B1 Gene Polymorphisms With Outcomes in SARS-CoV-2 Infected Patients

Conditions
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Covid19

Intervention / Treatment
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* Genetic: Expression of receptors and activating proteases
* Genetic: Polymorphism of the HSD3B1


Participation Criteria
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Eligibility Criteria
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Sub-project 1 Inclusion Criteria: Availability of RNA extracted from nasopharyngeal swabs taken from subjects tested for COVID-19; Subject is aged 18 years or over; Written informed consent (for SARS-CoV-2 positive patients only; see §5 for further details). Exclusion Criteria: - Documented refusal. Sub-project 2 Inclusion Criteria: Female and male hospitalized SARS-CoV-2 patients; Patient is aged 18 years or over; Availability of archival tissue samples collected at any time before SARS-CoV-2 infection for any clinical reason; Clinico-pathological characteristics of the COVID-19 and clinical outcomes recorded in the EOC and Clinica Luganese Moncucco database; Written informed consent (see §5 for further details). Exclusion Criteria: - Documented refusal.

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients tested for COVID-19<br>The nasopharyngeal swabs taken from patients tested for Covid-19 who resulted infected and non-infected will be analyzed to evaluate the expression of receptors and activating proteases mediating SARS-CoV-2. | Genetic: Expression of receptors and activating proteases<br>* Level of expression of the mRNA of the genes encoding ACE2, TMPRSS2, TMPRSS4 and AR along with reference genes (beta-actin and EPCAM) in nasopharyngeal swabs taken from patients tested for COVID-19<br>|
| Patients with mild-moderate and severe SARS-CoV-2 infection<br>Formalin-fixed paraffin will be analysed to determine the association between polymorphism of the HSD3B1 gene and outcomes in COVID-19 affected patients | Genetic: Polymorphism of the HSD3B1<br>* Formalin-fixed paraffin embedded tissue blocks will be amplified using polymerase chain reaction (PCR) based experiments followed by direct sequencing (Sanger sequencing)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of receptors and activating proteases | Determination of the level of expression of the mRNA genes | 1 year | 
| Prevalencen of olymorphisms of the HSD3B1 | Determination of the prevalence of polymorphisms of the HSD3B1 patients with severe and mild-moderate SARS-CoV-2 infection | 1 year | 
| Association of polymorphisms of the HSD3B1 | Evaluation of the association of polymorphisms of the HSD3B1 with clinico-pathological parameters | 1 year |