SARS-CoV2 is the virus which causes COVID-19, the form of coronavirus which is now a global pandemic. The gene ACE2 is involved when SARS-CoV2 infection occurs and the eye is an important possible place of entry for the virus to get into the body. It is thought that the virus enters the eye through ACE2, but this remains unclear. We will look at gene expression in eye tissue to identify whether ACE2 is important in the eye and generate a picture of biomarkers of the eye which may predict disease severity. This will help in understanding the first steps in the mechanism of infection and potential targets for therapies. We will be using excess surgical tissue from the eyes of non COVID-19 patients undergoing surgery for other reasons.

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.

Population-wide prophylactic vaccination is the principal means of quelling the COVID-19 pandemic. For this to succeed, knowledge of vaccine efficacy is imperative. Patients with lymphoid malignancies have an increased mortality risk from COVID-19. Many patients are apparently cured but have long-term immune defects. Our lack of knowledge of COVID-19 vaccination responses confers a morbidity and mortality risk in this population and significant societal impact. This study will assess COVID-19 vaccine efficacy defined by immunological responses (anti-spike IgG, virus neutralisation, T-cell recall).