SARS-CoV-2 has emerged as a global pandemic in 2020. There are no effective treatments and an effective vaccine has not been developed. Whilst many patients recover without need for hospitalisation, a small proportion go on to develop severe disease. A better understanding of the natural history of this disease will facilitate improved clinical management with the potential to identify options for intervention. This proposal is for the formal collection of characterisation data for patients tested for and/or admitted with a confirmed diagnosis of SARS-CoV-2 infection. This study responds to the need for a clear understanding of the natural history of this novel, emerging pandemic. Specifically phenotypic characterisation may enable application of personalised medical approaches, based on clinical course, to aid earlier identification of patients at risk of severe disease, and facilitate identification of potential targets for novel treatments. The collection and characterisation of these patients reflects a strong partnership between NHS and academic critical care and respiratory medicine in Southampton that acts as both a secondary and tertiary centre, with support from the digital experimental cancer medicine team at the University of Manchester.

This study is part of a collaborative UK immunology network to understand how the immune system can protect against COVID-19 and develop relevant tests to help identify patients with better or worse outcomes following exposure to SARS-CoV-2. Our role is to investigate the part of the early warning system of the immune system: “the innate immune system”, and its response to COVID-19. We wish to study this part of the immune system in detail because other studies have overlooked this important part of the immune response to COVID-19. The cells of the innate immune system are present in a primed “ready-to-go” state in most individuals. However, it is possible that other infections, and even vaccines such as BCG, can give these cells a heightened state of readiness called “trained immunological memory”. We wish to test if individuals who have better outcomes from COVID-19, or are protected from infection have stronger innate immune systems with more cells in this “trained” state than those who have worse outcomes. Similarly, we wish to study if the innate immune system can determine which individuals will have more severe outcomes, such as respiratory failure. We will study this using assays of immune cell function and by phenotyping these cells at a molecular level. In this way, we will learn how the innate immune system responds to SARS-CoV-2 and investigate some of the molecular mechanisms involved. It is hoped that information from this work can inform useful immunological tests that will help to decide which patients are protected from infection and which patients may develop severe COVID-19 disease.