SARS COV2 vaccine ResPonse In Obesity - SCORPIO study

The best way to protect people from COVID-19 is by vaccination. Vaccines trigger a person's immune system so it is primed to respond efficiently if the person comes into contact with the virus again. It is important to know whether vaccines against the SARS-CoV-2 virus, which causes COVID-19, work as well in people with underlying health conditions as they do in healthy people.

The aim of this study is to test whether the SARS-CoV-2 vaccine works equally well in people with weight problems and diabetes. People who are overweight/obese and those who have diabetes are much more likely to become seriously ill if they develop COVID-19 infection. If vaccines don't work as well, then 10 million people in the UK will still be at high risk of COVID-19 infection, when they think they are protected.

By bringing together world-leading doctors and researchers in obesity/diabetes and infection/immunity, this research project will establish whether the immune response is different in people who are overweight or have diabetes. Previous research with other vaccines such as the flu vaccine, suggests that the immune response might be weaker or may not last as long in people with these health conditions.

We think it is likely that some people with obesity/diabetes will have a weak immune response and we want to see if losing weight can boost the vaccine response. If it does, then this would provide a strong incentive for extra help and support for weight loss treatments, which are currently only available to a small number of people who have really struggled with their weight for decades.

Over the next year, we will invite 200 people who are having different weight loss treatments (intense diet and surgery) as part of their routine medical care to take part in the SCORPIO study. If they agree, we will take a few extra blood samples to look at whether their vaccine response changes after weight loss treatment. We will collect information about their height and weight, medical conditions and look in detail at the immune system, blood sugar levels and hormones.

Based on our experience, it is likely some people will lose a small amount of weight while others will lose a lot of weight. We will study the impact of weight loss on the immune response to the first and second dose of the COVID-19 vaccine.

We will keep a close eye on people in the study during their regular clinic visits and if they develop symptoms of COVID-19 infection, we will ensure they receive prompt medical care. We will also arrange for genetic sequencing to see if particular variants of the virus are affecting people with weight problems and diabetes.

We will compare these results with normal weight people based locally and compare these results with colleagues around the country to make best use of the available information

At the end of the study, we will establish whether the immune response is weaker in people with obesity/diabetes, which groups of people are most at risk (e.g. is it people with the highest blood sugars?) and find out if weight loss can rapidly improve the immune response to the vaccine, giving people better protection against COVID-19.

Over 20% of the UK population are obese; people with obesity have substantially higher morbidity and mortality from COVID-19 infection. As obese people have reduced immune responses to other vaccines (influenza, hepatitis), we hypothesise that obesity may similarly reduce the protection offered by SARS-CoV-2 vaccines by impairing cellular immunity, reducing initial antibody titres and/or by causing an acceleration of the natural decline in antibody titres.

We will address this question by recruiting a cohort of 200 patients with severe obesity (Body Mass Index (BMI)>40 kg/m2) - the population we suspect is at highest risk - from clinics in Cambridge University Hospital and Kings College Hospital, London (SCORPIO study). We will compare their vaccine responses (T and B cell-mediated immunity, neutralisation assay, anti-Spike and Nucleocapsid antibodies, inflammatory cytokines) to 1500 normal weight people studied using the same assays. To comprehensively investigate the impact on vaccine responses of BMI across the full range from overweight, to obese and severely obese, we will collaborate with a network of investigators leading existing UK studies to perform a meta-analysis of 50,000 people. We will seek to identify predictive nutritional and metabolomic biomarkers (obese responders vs non-responders) and test whether weight loss (shown to improve response to the influenza vaccine in mice) can improve vaccine responses in obese people. This ambitious programme of research will deliver new insights into the relationship between BMI, metabolic health and the response to SARS-CoV-2 vaccines and inform public health policy in this area, within 12 months.