Immune biomarkers of outcome from COVD-19 (IBOC) [COVID-19]
Research type
Research Study
Full title
Immune dysfunction in COVID-19: investigation of mechanisms and identification of immune biomarkers of clinical outcome
IRAS ID
282949
Contact name
Ashwin Dhanda
Contact email
Sponsor organisation
University Hospital Plymouth NHS Trust
Duration of Study in the UK
0 years, 9 months, 0 days
Research summary
Research Summary
A global pandemic has been declared with over 1 million infections and many thousands of deaths. The virus, SARS-CoV2, leads to coronavirus disease 2019 (COVID-19), which mainly affects the breathing system. Around 1 in every 5 people with COVID-19 have more severe infection needing treatment in hospital. Up to half of them require help with breathing in an intensive care unit. Information we have so far about COVID-19 suggests that people with underlying conditions, such as high blood pressure and heart disease, or older people are at higher risk of having severe illness. We do not yet understand why but think it may be related to the immune system.\n\nSARS-CoV2 activates the immune system causing inflammation in the lungs, which is also seen in circulating immune cells in the blood. Preliminary reports show that the response of the immune system is inappropriate; it is overactive but also poorly responsive (exhausted). Changes in the type and function of immune cells have been linked to increased risk of severe disease or death from COVID-19. \n\nIn this study, we aim to look for markers of immune function when a person first attends hospital, which can be used to predict whether they will go on to have a more severe infection. This will help treat patients more effectively, for example, by moving high risk patients to an intensive care setting at an early stage. We will investigate the immune system in detail in 200 patients with COVID-19 attending University Hospitals Plymouth. We will look for changes in the number, type and function of circulating immune cells and measure whether these changes are linked to severity of the infection or death. We will use established techniques to measure immune function that could be rapidly put into routine hospital care to help guide treatment for individual patients.Summary of Results
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is asymptomatic or mild in most but leads to moderate or severe disease requiring oxygen therapy in approximately 1 in 5 people with symptomatic infection. Mortality is associated with age and may be driven by failure of the immune system caused by exhaustion and premature ageing of cells (senescence). Identifying biomarkers of immune function that can predict an individual’s response to the virus remains an important goal.We aimed to determine whether biomarkers of immune function and immune cell exhaustion and senescence could predict clinical outcomes of unvaccinated patients admitted to hospital with moderate to severe COVID-19.
We used a blood test of overall immune function called QuantiFERON Monitor (QFM) as well as looking at specific markers of exhaustion and senescence on immune cells. We compared results to 12 healthy volunteers.
Forty-one patients were recruited to the study, of which 1 required intensive care unit admission and seven died during the hospital admission. Patients with COVID-19 had much lower QFM results compared to healthy volunteers but they did not predict death or the need for intensive care. Examining a range of immune cell markers showed that markers of exhaustion (PD-1) and senescence (CD57) were higher on immune cells from patients compared to healthy volunteers.
These results show that patients with COVID-19 had an impaired immune response and their immune cells showed signs of exhaustion and ageing. These findings can be studied further to understand how SARS-CoV2 causes these changes and to identify new ways of treating it.
REC name
Yorkshire & The Humber - Bradford Leeds Research Ethics Committee
REC reference
20/YH/0150
Date of REC Opinion
22 Apr 2020
REC opinion
Further Information Favourable Opinion