COVID-19GEN-COVIDNCT04549831
Genetic Bases of COVID-19 Clinical Variability
An observational study of COVID-19, run by University of Siena at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Massive parallel sequencing of host genome
- How many people
- 2,000 participants
- Where
- 1 siteItaly
- Study dates
- 8 Apr 2020to 8 Apr 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hospitalized patients, outpatients, asymptomatic individuals
Who may be able to join
- Age > or equal to 18
- SARS-CoV-2 PCR positive on swab
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University of Siena
Siena, 53100
Alessandra Renieri, MD, PhD, 00390577233303, alessandra.renieri@unisi.it
Francesca Mari, MD, PhD
About this study
Official title: 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.
Read more
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.
Read the 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).
- Conditions
- COVID-19
- Being tested
- Massive parallel sequencing of host genome
- Keywords
- COVID-19, SARS-CoV-2, Host Genetics, Genetic susceptibility
- Medical subject headings
- COVID-19, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Massive parallel sequencing of host genomeGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: Massive parallel sequencing of host genome |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 years
Secondary outcomes (1)
To identify the genetic determinants of COVID-19 clinical trajectories.
Identification of candidate gene(s) responsible for the COVID-19 clinical trajectories.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start8 Apr 2020
- Primary completion31 Dec 2022 (estimated)
- Study completion8 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Siena
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione IRCCS Policlinico San Matteo di Pavia, 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, ASST Valtellina e Alto Lario, Azienda USL Toscana Sud Est, ULSS1 Dolomiti, Belluno, Asst Degli Spedali Civili Di Brescia, IRCCS Casa Sollievo della Sofferenza, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Ospedale Luigi Curto, Polla, Istituto Auxologico Italiano, CEINGE Biotecnologie Avanzate, Napoli
- Responsible party
- Principal investigator, Francesca Mari, Azienda Ospedaliera Universitaria Senese
- Investigators
- Francesca Mari, MD, PhD, Principal investigator, University of Siena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549831
- Sponsor's protocol ID
- 16917
- Acronym
- GEN-COVID
- Status last verified
- Nov 2022
- First submitted
- 11 Sep 2020
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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)
Publications
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.
PubMed 31978945Wu 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.
PubMed 32091533Bergantini L, Baldassarri M, d'Alessandro M, Brunelli G, Fabbri G, Zguro K, Degl'Innocenti A; GEN-COVID Multicenter study; Fallerini C, Bargagli E, Renieri A. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder. Respir Res. 2023 Jun 16;24(1):158. doi: 10.1186/s12931-023-02458-7.
PubMed 37328761Fallerini 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.
PubMed 33650967
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of the Genetic Bases Determining COVID-19 Clinical Variability in the Italian Population
- ClinicalTrials.gov ID
- NCT04549831
- Acronym / sponsor ID
- GEN-COVID / 16917
- Conditions
- COVID-19
- Keywords
- COVID-19, SARS-CoV-2, Host Genetics, Genetic susceptibility
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University of SienaUniversity, hospital or other
- Collaborators
- Fondazione IRCCS Policlinico San Matteo di Pavia, 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, ASST Valtellina e Alto Lario, Azienda USL Toscana Sud Est, ULSS1 Dolomiti, Belluno, Asst Degli Spedali Civili Di Brescia, IRCCS Casa Sollievo della Sofferenza, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Ospedale Luigi Curto, Polla, Istituto Auxologico Italiano, CEINGE Biotecnologie Avanzate, Napoli
- Study start
- 8 Apr 2020 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 8 Apr 2026 (estimated)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SARS-CoV-2 PCR positive individuals | – | Genetic: Massive parallel sequencing of host genomeAdult (> o equal to 18 years) SARS-CoV-2 PCR positive individuals with different clinical outcome: from asymptomatic to severely affected COVID-19 patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospitalized patients, outpatients, asymptomatic individuals
Key inclusion criteria (2 listed)
- Age > or equal to 18
- SARS-CoV-2 PCR positive on swab
Key exclusion criteria (1 listed)
- none
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Massive parallel sequencing of host genomeMassive 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. | Genetic | SARS-CoV-2 PCR positive individuals |
Primary outcome
To identify the genetic determinants of COVID-19 severity
Time frame: 6 years
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.
1 secondary outcome
To identify the genetic determinants of COVID-19 clinical trajectories.
Time frame: 6 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Background: PubMed 31978945Zhu 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.
- Background: PubMed 32091533Wu 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.
- Derived from this study: PubMed 37328761Bergantini L, Baldassarri M, d'Alessandro M, Brunelli G, Fabbri G, Zguro K, Degl'Innocenti A; GEN-COVID Multicenter study; Fallerini C, Bargagli E, Renieri A. Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder. Respir Res. 2023 Jun 16;24(1):158. doi: 10.1186/s12931-023-02458-7.
- Derived from this study: PubMed 33650967Fallerini 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.
- GEN-COVID: Impact of Host Genome on COVID-19 clinical variabilityLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesca Mari, MD, PhD principal investigator
University of Siena
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by University of Siena at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alessandra Renieri, MD, PhD (00390577233303, alessandra.renieri@unisi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify the genetic determinants of COVID-19 severity (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04549831, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.