Identifying host molecular endotypes associated with diverse COVID-19 outcomes and new variants in a longitudinal multiomics cohort study of 1000 patients

The COVID-19 pandemic has had a huge impact on people's lives all over the world. As of April 2021, more than 130 million people have been infected with the virus and over 2.8 million have lost their lives because of COVID-19 globally (data from the Johns Hopkins University Coronavirus Resource Center, accessed on April 1, 2021). While vaccination is underway in most well-resourced countries, the virus is not expected to be eradicated in the short to medium term. Understanding the diverse short- and long-term outcomes of COVID-19 remains important. For example, it is currently not possible to predict who will become long-haulers and continue to experience symptoms that last for weeks or even months. The goal of this project is to better understand the molecular underpinnings of diverse patient outcomes in COVID-19 and develop molecular diagnostics that can identify specific patient groups for targeted management (e.g., those likely to require oxygen support or at greater risk of developing long-COVID-19). Early identification of such patients would improve patient care, allow for better allocation of scarce resources to those who need them most, and may even result in the development of novel, more-personalized, treatments. We are uniquely positioned to address this thanks to existing access to the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study. IMPACC is a unique resource that includes comprehensive molecular profiling at many timepoints during infection (enrollment, days 4, 7, 14, 21, 28 post-COVID-19 diagnosis), as well as in long-term follow-up (months 3, 6, 9, and 12), on a large group (n = 1,223) of COVID-19 patients. Crucially, the size of this cohort allows for capture of disease variability driven by emerging variants, as well as the effect of vaccines in diminishing disease. The molecular signatures we develop will be validated using ongoing Canadian research cohorts.