Clinical trial NCT04549831: Genetic Bases of COVID-19 Clinical Variability
Official title: Identification of the Genetic Bases Determining COVID-19 Clinical Variability in the Italian Population
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: COVID-19
Keywords: COVID-19
SARS-CoV-2
Host Genetics
Genetic susceptibility
Lead sponsor: University of Siena
Sponsor class: OTHER
Collaborators: name: Fondazione IRCCS Policlinico San Matteo di Pavia
name: Ospedale San Donato, Arezzo
name: Ospedale della Misericordia
name: Azienda Ospedaliera Ospedale Maggiore di Crema
name: University of Modena and Reggio Emilia
name: ASST Fatebenefratelli Sacco
name: Azienda Ospedaliera di Perugia
name: Ospedale dell'Angelo, Venezia-Mestre
name: Azienda Ulss 2 Marca Trevigiana
name: Cardarelli Hospital
name: Azienda Ospedaliera dei Colli
name: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
name: Istituto Giannina Gaslini
name: Istituti Ospitalieri di Cremona
name: IRCSS Lazzaro Spallanzani, Roma
name: ASST Santi Paolo e Carlo
name: ASST Valtellina e Alto Lario
name: Azienda USL Toscana Sud Est
name: ULSS1 Dolomiti, Belluno
name: Asst Degli Spedali Civili Di Brescia
name: IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Ospedale Luigi Curto, Polla
name: Istituto Auxologico Italiano
name: CEINGE Biotecnologie Avanzate, Napoli
First posted: 2020-09-16
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitalized patients, outpatients, asymptomatic individuals

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).

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* none

Primary outcomes:
measure: To identify the genetic determinants of COVID-19 severity
timeFrame: 6 years
Secondary outcomes:
measure: To identify the genetic determinants of COVID-19 clinical trajectories.
timeFrame: 6 years
Other outcomes:
Locations:
city: Siena
country: Italy
facility: University of Siena
Study officials:
affiliation: University of Siena
name: Francesca Mari, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
citation: 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.