Genetic Predisposition to DiseaseNCT04390269
Immunogenetics Predictors With COVID-19
An observational study of Genetic Predisposition to Disease, run by Mansoura University at 1 site in Egypt.
Trial summary
Background: There is a current worldwide outbreak of the novel coronavirus Covid-19 which originated from Wuhan in China and has now spread to 6 continents including 210 countries. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Genetic Predisposition to Disease
- How many people
- 200 participants
- Where
- 1 siteEgypt
- Study dates
- 10 Sep 2020to 9 May 2022
- 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
- Adult, Older adult
Study population: They will evaluate the clinical usefulness of the application of different diagnostic tests, monitoring tools and therapeutic options in clinical practice to improve the disease outcomes and reduce the costs of the disease burdens. In brief, the approach will consist of the following steps: 1. Early diagnosis of patients at risk of COVID 19 evolution and their surveillance and monitoring by different means. 2. Specific laboratory analysis for different genetic molecular tests for COVID 19 infection. 3. Monitoring the genetic molecular tests in the follow-up periods.
Who may be able to join
- Adult subjects (> 18 years old) with COVID 19 infection.The patients will be classified on the basis of the severity of the disease.
Who cannot join
- -patients have symptoms of fever and /or respiratory with negative PCR for COVID-19.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Mansoura Faculty of Medicine
Al Mansurah, Dakahlyia, 35516
Mahmoud El-Bendary, M.D, 00201002592205, mmelbendary@gmail.com
About this study
Official title: Various Molecular Markers With Predictive and Prognostic Significance in COVID-19 Outcome
Background: There is a current worldwide outbreak of the novel coronavirus Covid-19 which originated from Wuhan in China and has now spread to 6 continents including 210 countries. There is still a lack of any report about severe acute respiratory syndromes (SARS-CoV-2) genetic polymorphisms which are associated with the susceptibility to infection. In addition, gene polymorphisms of MBL (mannose-binding lectin) associated with antigen presentation are related to the risk of SARS-CoV infection. Aim: To investigate the association of different genetic markers of different mechanisms of viral pathogenesis with the outcome of COVID-19. Methods: The study will include one hundred patients diagnosed as COVID-19. Biological blood samples will be taken for routine diagnostic analysis, routine molecular testing using Real-time polymerase chain reaction (PCR), Allelic discrimination and genotyping analysis. Outcome: Different genetic markers could play a role in the outcome and prognosis of COVID-19 viral infection.
Read the detailed description
There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 210 countries. Coronaviruses (CoVs), is a large family of single-stranded RNA viruses, can infect animals and humans, causing respiratory, gastrointestinal, hepatic, and neurologic diseases. Coronaviruses are a group of enveloped viruses with a positive-sense single-stranded RNA genome (26-39 kb). Four coronavirus genera (α, β, γ, δ) have been determined so far, with human coronaviruses (HCoVs) detected in the α coronavirus (HCoV-229E and NL63) and β coronavirus (e.g MERS-CoV and SARS-CoV) genera. This isolated novel β-CoV shows less than 80% similarity to the sequence of two bat-derived severe acute respiratory syndromes (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, and about 50% identity to the sequence of a middle east respiratory syndrome (MERS-CoV). Patients with COVID-19 show general clinical manifestations including fever, dry cough, dyspnea, myalgia, fatigue, normal or decreased leukocyte counts, and radiographic evidence of pneumonia. After the virus enters the host cells, the viral RNA genome is released into the cytoplasm and is translated into two polyproteins and structural proteins, after which the viral genome begins to replicate. When the virus enters the host cells, its antigen will be presented to the antigen presentation cells(APC), which is a central part of the body's anti-viral immunity. Antigenic peptides are presented by major histocompatibility complex (MHC; or human leukocyte antigen (HLA) in humans) and then recognized by virus-specific cytotoxic T lymphocytes (CTLs). Hence, the understanding of the antigen presentation of SARS-CoV-2 will help our comprehension of COVID-19 pathogenesis. However, there is still a lack of any report about SARS-CoV-2, we can get a lot of information from previous researches on SARS-CoV and MERS-CoV. The antigen presentation of SARS-CoV mainly depends on MHC I molecules, but MHC II also contributes to its presentation.
These findings may provide valuable information for the rational design of vaccines against SARS-CoV-2. One of the main mechanisms for ARDS is the cytokine storm, the deadly uncontrolled systemic inflammatory response resulting from the release of huge amounts of pro-inflammatory cytokines and chemokines by immune effector cells in SARS-CoV infection. Better survive in host cells, SARS-CoV and MERS-CoV use multiple strategies to avoid immune responses. The evolutionarily conserved microbial structures called pathogen-associated molecular patterns can be recognized by pattern recognition receptors (PRR).
The antigen presentation can also be affected by the coronavirus. For example, gene expression related to antigen presentation is down-regulated after MERS-CoV infection. Therefore, destroying the immune evasion of SARS-CoV-2 is imperative in its treatment and specific drug development.
- Conditions
- Genetic Predisposition to Disease
- Keywords
- COVID-19, CYTOKINES, CHEMOKINES, GENETIC POLYMORPHISM, Immunity
- Medical subject headings
- Genetic Predisposition to Disease, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Infected group | The infected group will be classified according to the severity whether mild ,moderate or severe | |
| susceptible (non infected | This group either exposed and not infected . | |
| control group | normal control subject |
What is being measured
The primary outcome is the main question the study is designed to answer.
for the patients
To assess genetic mutation via detection of genetic polymorphisms of ACE2 in patients and control to detect what alleles will be associated with the susceptibility to COVID-19 and what alleles will be associated with clearance or protection from infections. using allelic discrimination SSCP (i.e Real-time PCR and genetic sequencer).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2020
- Study start10 Sep 2020
- Primary completion10 Oct 2021 (estimated)
- Study completion9 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Genetic Predisposition to DiseaseStudies 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
- Cross-sectional
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahmoud Elbendary, Mansoura University
- Investigators
- Mahmoud El-Bendary, M.D, Principal investigator, Mansoura University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04390269
- Sponsor's protocol ID
- R.20.05.830.R1
- Status last verified
- May 2020
- First submitted
- 12 May 2020
- Last updated
- 24 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.
PubMed 31986261Zhang J, Zhou L, Yang Y, Peng W, Wang W, Chen X. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet Respir Med. 2020 Mar;8(3):e11-e12. doi: 10.1016/S2213-2600(20)30071-0. Epub 2020 Feb 13. No abstract available.
PubMed 32061335Xu Z, Li S, Tian S, Li H, Kong LQ. Full spectrum of COVID-19 severity still being depicted. Lancet. 2020 Mar 21;395(10228):947-948. doi: 10.1016/S0140-6736(20)30308-1. Epub 2020 Feb 14. No abstract available.
PubMed 32066525Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):541-543. doi: 10.1038/s41423-020-0401-3. Epub 2020 Mar 17. No abstract available.
PubMed 32203186Lu KL, Chen S, Leung LP. Initial Experience of an Emergency Department in Shenzhen in Responding to the Emerging Wuhan Coronavirus Pneumonia. Ann Emerg Med. 2020 Apr;75(4):556. doi: 10.1016/j.annemergmed.2020.02.006. No abstract available.
PubMed 32216893Hu Y, Deng H, Huang L, Xia L, Zhou X. Analysis of Characteristics in Death Patients with COVID-19 Pneumonia without Underlying Diseases. Acad Radiol. 2020 May;27(5):752. doi: 10.1016/j.acra.2020.03.023. Epub 2020 Apr 7. No abstract available.
PubMed 32273135Chen C, Zhou Y, Wang DW. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020 May;45(3):230-232. doi: 10.1007/s00059-020-04909-z. No abstract available.
PubMed 32140732
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Various Molecular Markers With Predictive and Prognostic Significance in COVID-19 Outcome
- ClinicalTrials.gov ID
- NCT04390269
- Acronym / sponsor ID
- R.20.05.830.R1
- Conditions
- Genetic Predisposition to Disease
- Keywords
- COVID-19, CYTOKINES, CHEMOKINES, GENETIC POLYMORPHISM, Immunity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- 10 Sep 2020 (actual)
- Primary completion
- 10 Oct 2021 (estimated)
- Study completion
- 9 May 2022 (estimated)
- First posted
- 15 May 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.
Background: There is a current worldwide outbreak of the novel coronavirus Covid-19 which originated from Wuhan in China and has now spread to 6 continents including 210 countries. There is still a lack of any report about severe acute respiratory syndromes (SARS-CoV-2) genetic polymorphisms which are associated with the susceptibility to infection. In addition, gene polymorphisms of MBL (mannose-binding lectin) associated with antigen presentation are related to the risk of SARS-CoV infection. Aim: To investigate the association of different genetic markers of different mechanisms of viral pathogenesis with the outcome of COVID-19. Methods: The study will include one hundred patients diagnosed as COVID-19. Biological blood samples will be taken for routine diagnostic analysis, routine molecular testing using Real-time polymerase chain reaction (PCR), Allelic discrimination and genotyping analysis. Outcome: Different genetic markers could play a role in the outcome and prognosis of COVID-19 viral infection.
Detailed description
There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 210 countries. Coronaviruses (CoVs), is a large family of single-stranded RNA viruses, can infect animals and humans, causing respiratory, gastrointestinal, hepatic, and neurologic diseases. Coronaviruses are a group of enveloped viruses with a positive-sense single-stranded RNA genome (26-39 kb). Four coronavirus genera (α, β, γ, δ) have been determined so far, with human coronaviruses (HCoVs) detected in the α coronavirus (HCoV-229E and NL63) and β coronavirus (e.g MERS-CoV and SARS-CoV) genera. This isolated novel β-CoV shows less than 80% similarity to the sequence of two bat-derived severe acute respiratory syndromes (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, and about 50% identity to the sequence of a middle east respiratory syndrome (MERS-CoV). Patients with COVID-19 show general clinical manifestations including fever, dry cough, dyspnea, myalgia, fatigue, normal or decreased leukocyte counts, and radiographic evidence of pneumonia. After the virus enters the host cells, the viral RNA genome is released into the cytoplasm and is translated into two polyproteins and structural proteins, after which the viral genome begins to replicate. When the virus enters the host cells, its antigen will be presented to the antigen presentation cells(APC), which is a central part of the body's anti-viral immunity. Antigenic peptides are presented by major histocompatibility complex (MHC; or human leukocyte antigen (HLA) in humans) and then recognized by virus-specific cytotoxic T lymphocytes (CTLs). Hence, the understanding of the antigen presentation of SARS-CoV-2 will help our comprehension of COVID-19 pathogenesis. However, there is still a lack of any report about SARS-CoV-2, we can get a lot of information from previous researches on SARS-CoV and MERS-CoV. The antigen presentation of SARS-CoV mainly depends on MHC I molecules, but MHC II also contributes to its presentation.
These findings may provide valuable information for the rational design of vaccines against SARS-CoV-2. One of the main mechanisms for ARDS is the cytokine storm, the deadly uncontrolled systemic inflammatory response resulting from the release of huge amounts of pro-inflammatory cytokines and chemokines by immune effector cells in SARS-CoV infection. Better survive in host cells, SARS-CoV and MERS-CoV use multiple strategies to avoid immune responses. The evolutionarily conserved microbial structures called pathogen-associated molecular patterns can be recognized by pattern recognition receptors (PRR).
The antigen presentation can also be affected by the coronavirus. For example, gene expression related to antigen presentation is down-regulated after MERS-CoV infection. Therefore, destroying the immune evasion of SARS-CoV-2 is imperative in its treatment and specific drug development.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Infected group | – | –The infected group will be classified according to the severity whether mild ,moderate or severe |
| susceptible (non infected | – | –This group either exposed and not infected . |
| control group | – | –normal control subject |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- They will evaluate the clinical usefulness of the application of different diagnostic tests, monitoring tools and therapeutic options in clinical practice to improve the disease outcomes and reduce the costs of the disease burdens. In brief, the approach will consist of the following steps: 1. Early diagnosis of patients at risk of COVID 19 evolution and their surveillance and monitoring by different means. 2. Specific laboratory analysis for different genetic molecular tests for COVID 19 infection. 3. Monitoring the genetic molecular tests in the follow-up periods.
Key inclusion criteria (1 listed)
- Adult subjects (> 18 years old) with COVID 19 infection.The patients will be classified on the basis of the severity of the disease.
Key exclusion criteria (1 listed)
- -patients have symptoms of fever and /or respiratory with negative PCR for COVID-19.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
for the patients
Time frame: 2 years
To assess genetic mutation via detection of genetic polymorphisms of ACE2 in patients and control to detect what alleles will be associated with the susceptibility to COVID-19 and what alleles will be associated with clearance or protection from infections. using allelic discrimination SSCP (i.e Real-time PCR and genetic sequencer).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Background: PubMed 31986261Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.
- Background: PubMed 32061335Zhang J, Zhou L, Yang Y, Peng W, Wang W, Chen X. Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics. Lancet Respir Med. 2020 Mar;8(3):e11-e12. doi: 10.1016/S2213-2600(20)30071-0. Epub 2020 Feb 13. No abstract available.
- Background: PubMed 32066525Xu Z, Li S, Tian S, Li H, Kong LQ. Full spectrum of COVID-19 severity still being depicted. Lancet. 2020 Mar 21;395(10228):947-948. doi: 10.1016/S0140-6736(20)30308-1. Epub 2020 Feb 14. No abstract available.
- Background: PubMed 32203186Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, Dong XQ, Zheng YT. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):541-543. doi: 10.1038/s41423-020-0401-3. Epub 2020 Mar 17. No abstract available.
- Background: PubMed 32216893Lu KL, Chen S, Leung LP. Initial Experience of an Emergency Department in Shenzhen in Responding to the Emerging Wuhan Coronavirus Pneumonia. Ann Emerg Med. 2020 Apr;75(4):556. doi: 10.1016/j.annemergmed.2020.02.006. No abstract available.
- Background: PubMed 32273135Hu Y, Deng H, Huang L, Xia L, Zhou X. Analysis of Characteristics in Death Patients with COVID-19 Pneumonia without Underlying Diseases. Acad Radiol. 2020 May;27(5):752. doi: 10.1016/j.acra.2020.03.023. Epub 2020 Apr 7. No abstract available.
- Background: PubMed 32140732Chen C, Zhou Y, Wang DW. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020 May;45(3):230-232. doi: 10.1007/s00059-020-04909-z. No abstract available.
- Individual participant dataSharing planned: No
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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.
Mahmoud El-Bendary, M.D principal investigator
Mansoura University
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 Genetic Predisposition to Disease, run by Mansoura University at 1 site in Egypt.
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 1 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 24 Feb 2021. 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 Egypt. 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 Mahmoud El-Bendary, M.D (00201002592205, mmelbendary@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
for the patients (time frame: 2 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 NCT04390269, which also lists 7 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 24 Feb 2021.