Genetic Bases of COVID-19 Clinical Variability

NCT04549831 | Recruiting

• 1 other identifier: 16917
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

GEN-COVID multicenter study aims to identify the genetic variants of the host genome responsible for the clinical variability of patients with COVID-19. This variability to date is only partially related to the age and comorbidities of patients. The primary objective of the study is therefore to identify genetic variants associated with the severity of the disease, while the secondary objective consists in the identification of variants associated with longitudinal disease trajectories. This is a laboratory study that involves the conduct of genetic investigations, including whole exome sequencing and genome wide association studies, on human biological material from patients affected by COVID-19. Clinical information useful to describe the level of disease severity will be also collected for each enrolled patient. A total of at least 2,000 COVID-19 patients is expected to be included.

Conditions

COVID-19

Keywords

COVID-19; SARS-CoV-2; Host Genetics; Genetic susceptibility

Outcome Measures

Primary Outcomes (1)

• To identify the genetic determinants of COVID-19 severity

  Identification of one or more candidate gene(s) responsible for the severe outcome and subsequent use of it/them for prognostic purposes and preventive treatment and/or care.

  6 years

Secondary Outcomes (1)

• To identify the genetic determinants of COVID-19 clinical trajectories.

  6 years

Study Arms (1)

SARS-CoV-2 PCR positive individuals

Adult (\> o equal to 18 years) SARS-CoV-2 PCR positive individuals with different clinical outcome: from asymptomatic to severely affected COVID-19 patients.

Genetic: Massive parallel sequencing of host genome

Interventions

Massive parallel sequencing of host genome GENETIC

Massive parallel sequencing and genotyping of host genome of individuals infected with SARS-CoV-2 and showing different clinical outcomes from asymptomatic to severely affected patients in order to identify the genetic determinants of severe COVID-19 and the genetic protective factors.

SARS-CoV-2 PCR positive individuals

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

Hospitalized patients, outpatients, asymptomatic individuals

You may qualify if:

• Age \> or equal to 18
• SARS-CoV-2 PCR positive on swab

You may not qualify if:

• none

Sponsors & Collaborators

• University of Siena: lead
• Fondazione IRCCS Policlinico San Matteo di Pavia: collaborator
• Ospedale San Donato, Arezzo: collaborator
• Ospedale della Misericordia: collaborator
• Azienda Ospedaliera Ospedale Maggiore di Crema: collaborator
• University of Modena and Reggio Emilia: collaborator
• ASST Fatebenefratelli Sacco: collaborator
• Azienda Ospedaliera di Perugia: collaborator
• Ospedale dell'Angelo, Venezia-Mestre: collaborator
• Azienda Ulss 2 Marca Trevigiana: collaborator
• Cardarelli Hospital: collaborator
• Azienda Ospedaliera dei Colli: collaborator
• IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy: collaborator
• Istituto Giannina Gaslini: collaborator
• Istituti Ospitalieri di Cremona: collaborator
• IRCSS Lazzaro Spallanzani, Roma: collaborator
• ASST Santi Paolo e Carlo: collaborator
• ASST Valtellina e Alto Lario: collaborator
• Azienda USL Toscana Sud Est: collaborator
• ULSS1 Dolomiti, Belluno: collaborator
• Asst Degli Spedali Civili Di Brescia: collaborator
• IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• Ospedale Luigi Curto, Polla: collaborator
• Istituto Auxologico Italiano: collaborator
• CEINGE Biotecnologie Avanzate, Napoli: collaborator

Study Sites (1)

University of Siena

Siena, 53100, Italy

RECRUITING

Related Publications (4)

• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

  PMID: 31978945 BACKGROUND

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 BACKGROUND

• Bergantini L, Baldassarri M, d'Alessandro M, Brunelli G, Fabbri G, Zguro K, Degl'Innocenti A; GEN-COVID Multicenter study; Fallerini C, Bargagli E, Renieri A. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder. Respir Res. 2023 Jun 16;24(1):158. doi: 10.1186/s12931-023-02458-7.

  PMID: 37328761 DERIVED

• Fallerini C, Daga S, Mantovani S, Benetti E, Picchiotti N, Francisci D, Paciosi F, Schiaroli E, Baldassarri M, Fava F, Palmieri M, Ludovisi S, Castelli F, Quiros-Roldan E, Vaghi M, Rusconi S, Siano M, Bandini M, Spiga O, Capitani K, Furini S, Mari F; GEN-COVID Multicenter Study; Renieri A, Mondelli MU, Frullanti E. Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study. Elife. 2021 Mar 2;10:e67569. doi: 10.7554/eLife.67569.

  PMID: 33650967 DERIVED

Related Links

• Employing a Systematic Approach to Biobanking and Analyzing Genetic and Clinical Data for Advancing COVID-19 Research
• GEN-COVID: Impact of Host Genome on COVID-19 clinical variability

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and derivates such as plasma, serum, DNA, lymphocytes, lymphoblastic cell lines, naso/oro-pharyngeal swab and derivates such as RNA, DNA.

MeSH Terms

Conditions

COVID-19; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Francesca Mari, MD, PhD

  University of Siena

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandra Renieri, MD, PhD

CONTACT

00390577233303; alessandra.renieri@unisi.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2020
• First Posted: September 16, 2020
• Study Start: April 8, 2020
• Primary Completion: December 31, 2022
• Study Completion: April 8, 2026
• Last Updated: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Already available
• Access Criteria: Publicly available

Locations

IT (1)