Molecular mapping of SARS-CoV2 and the host response with multiomics mass spectrometry to stratify disease outcomes

This project forms part of an international level effort to understand the mechanisms of COVID-19 disease in the global population. Despite the considerable insight gained into the virus,SARS-CoV-2, at the genetic level, the key facets of the virus structure and its pathogenic effects remain to be determined. Equally molecular descriptors that contribute to disease progression are poorly defined, and have not yet been considered in testing strategies. Mass spectrometry (MS) can provide rapid, precise and reproducible diagnostic information at the molecular level (multiomics) that complements genomic information. In this project we will use MS to profile patient response to COVID-19 (with samples from NHS partners). This research will be exploited by our industrial project partners for diagnostic/prognostic testing protocols and for the development of vaccines and therapeutics. Research will constitute the UK effort in an international coalition initiated by the PI, COVID-19 MS, (currently over 600 members in 28 countries) who have agreed to share experience, protocols, materials and data. This next generation measurement approach is both transferable and accessible and through replication studies involving multiple partner labs we will overcome the accuracy, sensitivity issues of current lab- based approaches while also providing population data about individual risk to COVID-19. Our multiomics approach allows detailed structural information of the virus and its effect on the host using an intrinsic physical property - mass - unlike the indirect lab approaches currently employed. Outputs are multifold: we will refine testing approaches, stratify treatment options, determine isolation requirements and bring much needed speed into measurement aspects of novel therapeutic development programmes - for COVID-19 and future threats. Through our expertise in biomarker discovery and validation to profile disease mechanisms we possess the processing pipelines to extract maximum understanding from the data. As world leaders in protein structure analysis, we will structurally characterise virus:cell interactions, informing vaccine design and therapeutic intervention. Knowledge gained will be translatable to hospital testing laboratories for targeted assays, to biopharmaceutical companies for vaccine and therapeutics development, and for the development and quality control of reagents for biomarker or serological tests. Working with LGC Ltd. diagnostics and measurement companies (Waters, Thermo, Sciex, Bruker) and through CAMS the Community for Analytical and Measurement Science major Pharmaceutical companies (Pfizer, AstraZeneca , GSK, and Allergan) we will be able to scale up our methods and translate the outcomes to provide targeted assays to the NHS for biomarkers, to validate serological tests and for vaccine and therapeutic development embedding future resilience. The international effort is purposefully geographically spread allowing regional NHS lab access to enable rapid implementation. Finally, we established the COVID-19 MS Coalition to share sample processing protocols and to make all curated datasets open and accessible for global effort to combat this disease.