Prognostic plasma protein signature for early stratification of severe from non-severe COVID-19

We carried out blood proteomics on a COVID-19 cohort from Qatar and identified a protein signature consisting of 46 plasma proteins which predicts severity of disease. This signature, the COVID-19 molecular severity score, was cross-validated in an independent cohort from the USA which used the same technology we used; Olink. The manuscript describing this work is under review at Nature Communications and available as a preprint [https://europepmc.org/article/ppr/ppr294026]. In this project, we aim to generate direct validation data on the minimum set of proteins required for prognostication of COVID-19 severity. The project will use a more basic, standard, and quantitative immunoassay (ELISA) compared to the highly specialized Olink multiplex immunoassays. This will provide us broader pathways to develop the COVID-19 molecular severity score using different technologies and/or with commercial partners in a format amenable to diagnostic use and accreditation if needed. With the completion of this TDF, we will have the evidence that the quantitative levels (in pg/mL) of each of the 14 proteins in our signature, and the collective level of all the 14 proteins, are able to stratify COVID-19 severity. This data will enable the next step of development to design and test a single and simple assay in collaboration with suppliers (BioRad, ThermoFisher or others) or diagnostic companies (Roche, PerkinElmer, ThermoFisher or others). Funding this proposal will enable the development of an early predictive test to use in SARS-CoV-2 infected people to determine their individual risk for developing severe COVID-19. This will enable evidence-based triaging of SARS-CoV-2 infected individuals to plan the required care for patients predicted to have mild diseases compared to those predicted to suffer severe COVID-19 and plan earlier treatment to prevent severe symptoms or death. Moreover, the test has the potential to be used as treatment-monitoring tool as the COVID-19 molecular severity score decreases overtime as patients recover but continues to increase overtime in patients who are admitted to ICU and die from COVID-19. Finally, we also found that the molecular severity score was significantly higher in SARS-CoV-2 negative patients who displayed respiratory symptoms and died, presumably due to other infections. Altogether, the COVID-19 molecular severity score has several applications including optimizing of healthcare and associates costs particularly during endemics/pandemics and managing patients in a Personalized/Precision Medicine approach at hospital or ICU

Hamad Bin Khalifa University (HBKU)