Immunogenetics Predictors With COVID-19

Genetic Predisposition to Disease Clinical Trial

Official title: Various Molecular Markers With Predictive and Prognostic Significance in COVID-19 Outcome

Status Recruiting

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Disease Susceptibility
• Genetic Predisposition to Disease

• NCT number: NCT04390269
• Study type: Observational
• Source: Mansoura University
• Contact: Mahmoud El-Bendary, M.D
• Phone: 00201002592205
• Email: mmelbendary@gmail.com
• Status: Recruiting
• Start date: September 10, 2020
• Completion date: May 9, 2022