CASCADE: Profiling the Inflammatory Cascade of COVID-19

The immuno-inflammatory cascade is essential to define in COVID-19 patients to develop an intervention strategy to abrogate respiratory failure. For this study, four groups of patients have been identified to inform disease characterisation:

• Patients in the community
• Patients at hospital admission
• Rapidly deteriorating patients
• Ventilated, critically ill patients There is an urgent need to elucidate the dynamic peripheral blood signature including neutrophil, monocyte, lymphocyte and soluble mediators. Indeed recent data suggest that activation and subsequent exhaustion of cytotoxic T cells and emergence of GM-CSF+ CD4+ T cells and inflammatory monocytes and macrophages (in blood and BAL(1,2,3)) are associated with severe pathology in COVID-19 patients, however the fine kinetics of changes in these populations relative to disease progression are unknown.

In this study, samples will be obtained from NHS Lothian patients (in both primary care and hospital settings) who have tested positive for COVID-19 infection. Once consented, blood samples and (where possible) surplus clinical samples will be obtained from participants at defined time-points through the duration of their disease. Participants who rapidly deteriorate during their hospital admission will provide smaller, more frequent blood samples to permit profiling of the immunological/inflammatory response during deterioration.

Patients without COVID-19 but of comparable age and comorbid status will act as controls.

In-house assays will be used to measure and phenotype circulating immune cells, their activation status and cytokine production (focusing primarily on polymorphonuclear leukocytes, mononuclear phagocytes and lymphocytes) from peripheral blood samples obtained from participants at different stages of COVID-19 disease.