ASTERIX: Adaptive stratification of COVID19 to facilitate endotype-directed intervention studies

ABSTRACT

Introduction and Objectives: Severe coronavirus 19 disease (COVID 19) has rapidly emerged as a global health threat and, despite considerable advances, outcomes remain poor in many patients. Published data infers considerable heterogeneity, with 80% suffering minimal symptoms but a minority developing life-threatening disease. COVID 19 trials to-date have been necessarily broad but the emergence of established therapies (e.g. Dexamethasone) and distinct phenotypes (e.g. immune activated, prothrombotic) suggests that early stratification to licensed or trial agents might result in improved outcomes. The ASTERIX study aims to define disease endotypes, based on baseline biological signatures associated with COVID-19 pneumonia, development of respiratory failure and death, which could be targeted in future trials. Methods: >6,000 samples of blood, urine and respiratory secretions were collected and banked during the first wave of the COVID 19 pandemic in Glasgow. The cohort is organised into Tiers 0, 1 & 2 with each tier having an increasing number of samples available for downstream translational research. All tiers have the same associated comprehensive clinical data including comorbidity, ethnicity, blood results, imaging, prescription data and outcomes, including critical care support and survival. Results: Tier 0 contains 1,512 cases, Tier 1 (defined by having at least one surplus sample banked for downstream assays) contains ~1000 cases. Tier 2 (defined as having matched samples of serum, plasma and a buffy coat) contains 421 cases. Sample collation and data analysis is ongoing but preliminary review indicates a mortality rate of 29%, which is consistent with that reported in UK-wide COVID 19 series. The project team have made extensive links with collaborators and a scientific review board has been convened. The following projects are at various stages of approval and delivery (1) Host Epigenomics (2) Host Proteomics (3) Host Metabolomics (4) miRNA Outcome Signatures (5) Host Respiratory Microbiome (6) COVID 19 Coagulopathy. Conclusions: Data and banked samples will be used to develop endotypes (biological signatures derived from statistical models) associated with progression to key clinical outcomes. This information will be used to identify high-risk cohorts that could be targeted in future studies testing suitable interventions, as directed by the content of each signature.