Genetic Bases of COVID-19 Clinical Variability

COVID-19 Clinical Trial

— GEN-COVID  

Official title:

Identification of the Genetic Bases Determining COVID-19 Clinical Variability in the Italian Population

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04549831
• Other study ID #: 16917
• Status: Recruiting
• Start date: April 8, 2020
• Est. completion date: April 8, 2026

Study information

• Verified date: November 2022
• Source: University of Siena
• Contact: Alessandra Renieri, MD, PhD
• Phone: 00390577233303
• Email: alessandra.renieri[@]unisi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: April 8, 2026
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• none

Related Conditions & MeSH terms

• COVID-19

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
Italy	University of Siena	Siena

Sponsors (26)

Lead Sponsor

Collaborator

University of Siena

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

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To identify the genetic determinants of COVID-19 clinical trajectories.	Identification of candidate gene(s) responsible for the COVID-19 clinical trajectories.	6 years

External 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