In response to the global COVID-19 pandemic, Addenbrooke’s hospital – the teaching hospital of the University of Cambridge medical school – has gathered its resources in patient care and medical research. The infrastructure has been set up, that will enable a multitude of clinical research, alongside the critical patient care required for COVID-19 patients admitted to the hospital in April and May 2020.
Upon admission to Addenbrooke’s hospital, 200 patients will be enrolled in the NIHR BioResource COVID19 cohort, and complex biochemical, flow cytometry, a genomic and molecular analysis will be undertaken. The analysis includes collecting peripheral blood mononuclear cells (PBMC), where multiple aliquots for each of those 200 patients will be stored away. Samples will be linked to Addenbrooke’s electronic medical record system allowing the collection of comprehensive clinical data. Once patient outcomes are known, a subset of these samples will be defrosted and subjected to a battery of further tests, which will include single-cell genomics analysis as outlined below.
This project focuses on single-cell profiling for peripheral blood mononuclear cells (PBMC) taken from COVID-19 patients to establish full single-cell transcriptome, protein expression for 225 proteins, B-cell receptor, and T-cell receptor rearrangement status.
PBMCs from 80 individual patients will be profiled. 40 of those patients will have progressed to more severe disease, while the other 40 showed no progression. For 10 of the 40 patients that progressed to a more severe stage of the disease, two additional (sequential) samples will be taken to monitor changes in PBMCs associated with severe symptoms. Therefore, this setup entails profiling a total of 100 PBMC samples (80 admission samples and 2×10 disease progression samples).
The single-cell analysis will be performed using the latest multi-modal molecular profiling technology. Importantly, additional vials of viable PBMCs will be kept in storage for possible future analysis of further data types, including open chromatin.
The strategy outlined above will permit deep datamining of the single-cell data against all the clinical and immunological parameters, including patient outcomes. Possible discoveries may include new gene or protein signatures expressed at the time of hospital admission that can predict subsequent disease outcomes, which would allow the future focussing of clinical resources on the most at-risk patients. Moreover, gene/protein signatures associated with poor disease outcome may also highlight biological pathways to be targeted by existing drugs, thus providing new treatment options for this patient group. Finally, analysis of BCR and TCR receptor status will allow future investigations into how the immune system responds to COVID-19 and reveal what types of immune responses are associated with good/poor patient outcomes, providing essential clues for the design of successful immune- modulatory treatment regimens.
The research groups of Sarah Teichmann (Head of Cellular Genetics, Wellcome Sanger Institute) and John Marioni (European Bioinformatics Institute) will support initial data processing and analysis.
All raw and processed genomic data will be freely available to the global community fighting the COVID-19 pandemic.
The project is ongoing. First results are expected by the end of 2020.