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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Genetic: Expression of receptors and activating proteases; Genetic: Polymorphism of the HSD3B1

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Switzerland
  • Bellinzona, Switzerland, 6500
    • Oncology Institute of Southern Switzerland (IOSI)
  • Lugano, Switzerland, 6900
    • Clinica Luganese Moncucco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects tested for COVID-19

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients tested for COVID-19; 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; 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
Patients with mild-moderate and severe SARS-CoV-2 infection; 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; Formalin-fixed paraffin embedded tissue blocks will be amplified using polymerase chain reaction (PCR) based experiments followed by direct sequencing (Sanger sequencing)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ricardo Pereira Mestre
• Collaborators: Institute of Oncology Research (IOR); Istituto Cantonale di Patologia
• Investigators: Study Chair: Ricardo Pereira Mestre, MD, Oncology Institute of Southern Switzerland (IOSI)

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2020
• Primary Completion (Actual): February 21, 2023
• Study Completion (Actual): February 21, 2023

Study Registration Dates

• First Submitted: August 16, 2020
• First Submitted That Met QC Criteria: August 16, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Steroid delta-isomerase
• Other Study ID Numbers: COVID19-GeneExp

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No