Genetic Bases of COVID-19 Clinical Variability (GEN-COVID)

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

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.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Genetic: Massive parallel sequencing of host genome

Detailed 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).

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

• Study Contact: Name: Alessandra Renieri, MD, PhD; Phone Number: 00390577233303; Email: alessandra.renieri@unisi.it

Study Locations

• Italy
  • Siena, Italy, 53100
    • Recruiting
    • University of Siena
    • Contact: Alessandra Renieri, MD, PhD; Phone Number: 00390577233303; Email: alessandra.renieri@unisi.it
    • Principal Investigator: Francesca Mari, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized patients, outpatients, asymptomatic individuals

Description

Inclusion Criteria:

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

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify the genetic determinants of COVID-19 clinical trajectories.	Identification of candidate gene(s) responsible for the COVID-19 clinical trajectories.	6 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful 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

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 8, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): April 8, 2026

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (ACTUAL): September 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Genetic susceptibility; Host Genetics
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 16917

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Relevant information coming from the genetic results of the study will be made available to the scientific community through the Network of Italian Genomes (NIG)
• IPD Sharing Time Frame: Already available
• IPD Sharing Access Criteria: Publicly available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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