Genetic Bases of COVID-19 Clinical Variability

NCT ID: NCT04549831

Last Updated: 2022-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-04-08

Study Completion Date

2026-04-08

Brief Summary

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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.

Detailed Description

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The outbreak of the coronavirus disease 2019 (COVID-19), the Severe Acute Respiratory Syndrome caused by SARS-CoV-2, that first appeared in December 2019 in Wuhan, Huanan, Hubei Province of China, has resulted in millions of cases worldwide within a few short months, and rapidly evolving into a real pandemic. The COVID-19 pandemic represents an enormous challenge to the world's healthcare systems. Among the European countries, Italy was the first to experience the epidemic wave of SARS-CoV-2 infection, accompanied by a severe clinical picture and a mortality rate reaching 14%.

The disease is characterized by a highly heterogeneous phenotypic response to SARS-CoV-2 infection, with the large majority of infected individuals having only mild or even no symptoms. However, the severe cases can rapidly evolve towards a critical respiratory distress syndrome and multiple organ failure. The symptoms of COVID-19 range from fever, cough, sore throat, congestion, and fatigue to shortness of breath, hemoptysis, pneumonia followed by respiratory disorders and septic shocks.

The GEN-COVID is a multicentre academic observational study designed to collect and systematize biological samples and clinical data across multiple hospitals and healthcare facilities in Italy with the purpose of deriving patient-level phenotypic and genotypic data. The project aims to identify the genetic determinants of COVID-19 clinical variability studying host genetics. Genetic analyses will include Genome Wide Association Studies, performed by the Institute of Molecular Medicine in Finland (FIMM), and Whole Exome Sequencing (WES) performed by the University of Siena. SARS-CoV-2 infected individuals (swab virus PCR-positive) showing clinical different severity will be collected. In particular enrolled subjects will include only adults (subjects with age higher or equal to 18 years) with the following clinical status types: asymptomatic individuals, home care patients with mild symptoms and hospitalized patients (i-those requiring invasive ventilation; ii-those requiring non-invasive ventilation i.e. CPAP and BiPAP, and high-flows oxygen therapy; iii- those requiring conventional oxygen therapy, and iv-those not requiring oxygen therapy).

Funding. MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy; Private donors for COVID research (Italian D.L. n.18 March 17, 2020).

Conditions

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COVID-19

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Massive parallel sequencing of host genome

Intervention Type 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.

Interventions

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Massive parallel sequencing of host genome

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.

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* none
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role collaborator

Ospedale San Donato, Arezzo

UNKNOWN

Sponsor Role collaborator

Ospedale della Misericordia

OTHER

Sponsor Role collaborator

Azienda Ospedaliera Ospedale Maggiore di Crema

OTHER

Sponsor Role collaborator

University of Modena and Reggio Emilia

OTHER

Sponsor Role collaborator

ASST Fatebenefratelli Sacco

OTHER

Sponsor Role collaborator

Azienda Ospedaliera di Perugia

OTHER

Sponsor Role collaborator

Ospedale dell'Angelo, Venezia-Mestre

OTHER

Sponsor Role collaborator

Azienda Ulss 2 Marca Trevigiana

OTHER

Sponsor Role collaborator

Cardarelli Hospital

OTHER

Sponsor Role collaborator

Azienda Ospedaliera dei Colli

OTHER

Sponsor Role collaborator

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

OTHER

Sponsor Role collaborator

Istituto Giannina Gaslini

OTHER

Sponsor Role collaborator

Istituti Ospitalieri di Cremona

OTHER

Sponsor Role collaborator

IRCSS Lazzaro Spallanzani, Roma

UNKNOWN

Sponsor Role collaborator

ASST Santi Paolo e Carlo

OTHER

Sponsor Role collaborator

ASST Valtellina e Alto Lario

UNKNOWN

Sponsor Role collaborator

Azienda USL Toscana Sud Est

OTHER_GOV

Sponsor Role collaborator

ULSS1 Dolomiti, Belluno

UNKNOWN

Sponsor Role collaborator

Asst Degli Spedali Civili Di Brescia

OTHER

Sponsor Role collaborator

IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo

UNKNOWN

Sponsor Role collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role collaborator

Ospedale Luigi Curto, Polla

UNKNOWN

Sponsor Role collaborator

Istituto Auxologico Italiano

OTHER

Sponsor Role collaborator

CEINGE Biotecnologie Avanzate, Napoli

UNKNOWN

Sponsor Role collaborator

University of Siena

OTHER

Sponsor Role lead

Responsible Party

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Francesca Mari

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francesca Mari, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Siena

Locations

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University of Siena

Siena, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Alessandra Renieri, MD, PhD

Role: CONTACT

00390577233303

Facility Contacts

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Alessandra Renieri, MD, PhD

Role: primary

00390577233303

References

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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.

Reference Type BACKGROUND
PMID: 31978945 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32091533 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37328761 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33650967 (View on PubMed)

Related Links

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http://doi.org/10.1101/2020.07.24.20161307

Employing a Systematic Approach to Biobanking and Analyzing Genetic and Clinical Data for Advancing COVID-19 Research

http://sites.google.com/dbm.unisi.it/gen-covid

GEN-COVID: Impact of Host Genome on COVID-19 clinical variability

Other Identifiers

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16917

Identifier Type: -

Identifier Source: org_study_id

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