59721Development of an algorithm to stratify risk to Covid-19 by MHC haplotype.ClosedFeasibility StudiesInnovate UKMajor histocompatibility complex (MHC) genes underpin host response to pathogens, including Covid-19\. MHC proteins have a functional peptide binding groove (PBG) that binds foreign peptides (antigens) within a cell. Once bound, the MHC-antigen complex translocates to the surface of the cell, which then stimulate an immune response. MHC genes thus play a critical role in the the overall immune response. The three-dimensional structure of the PBG determines which regions of antigens are bound by MHC proteins. Thus, MHC haplotypes, and subsequent variability within the PBG, can change how the antigen is presented externally, thus directly impacting the shape of the antibody produced during an immune response. Recent work has identified marked variation in MHC haplotype distribution between geographical areas affected more or less severely by COVID-19, and within different ethnic populations. Not only might these haplotype differences underpin stronger or weaker host immune responses to Covid-19, they could also undermine serological testing - certain MHC haplotypes may present antigens in such a way that the host antibodies raised are weakly or not detectable by mass-produced serological tests. PXD is currently developing algorithms to predict likelihood of developing an immune response to implanted materials, based upon MHC haplotypes. PXD will leverage this expertise to create an MHC-based diagnostic tool with utility for: * identifying individuals that may be at heightened risk for a dysregulated (overly aggressive) response to Covid-19\. * identifying which commercial serological tests will give the most accurate results for their MHC haplotype. * use as a companion diagnostic by the pharmaceutical industry during therapeutic development. **INNOVATION:** Diagnostic algorithm for predicting immune response to Covid-19 antigens based on MHC haplotyping assay data combined with 3-D protein modelling. **TEAM:** * Carlos Echevarria, Respiratory Consultant, Royal Victoria Infirmary, Newcastle upon Tyne. * Stephen Wright, Clinical Director Research and Development, Consultant in Anaesthesia and Intensive Care, Newcastle Hospitals. * Dr Anthony Poles, Consultant Clinical Scientist and Head of the NHSBT Histocompatibilty & Immunogenetics laboratory, Bristol. * Heather Cordell, Professor of Statistical Genetics, Institute of Human Genetics, Newcastle University. * Rebecca Darlay, Research Associate, Institute of Human Genetics, Newcastle University. * Pravin Khalia. Consultant Anaesthetist and intensivist, University Hospital of North Tees. * Shonali Natu. Consultant Pathologist, University Hospital of North Tees (Some are funded as subcontractors; most are providing in-kind support).