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

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).


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.
SARS-CoV-2 PCR positive individuals

Eligibility Criteria

Inclusion Criteria: - Age > or equal to 18 - SARS-CoV-2 PCR positive on swab

Exclusion Criteria: - none

Eligibility Gender
Eligibility Age
Minimum: 18 Years

Alessandra Renieri, MD, PhD

Francesca Mari, MD, PhD
Principal Investigator
University of Siena

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