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.

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 ~ Maximum: N/A

University of Siena
Siena, Italy

Investigator: Alessandra Renieri, MD, PhD
Contact: 00390577233303

Investigator: Francesca Mari, MD, PhD


Alessandra Renieri, MD, PhD

Francesca Mari, MD, PhD, Principal Investigator
University of Siena

University of Siena
NCT Number
Host Genetics
Genetic susceptibility
MeSH Terms