The protection offered by COVID-19 vaccination declines more rapidly in people with severe obesity than in those with normal weight, scientists at the Universities of Cambridge and Edinburgh have found.
The study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.
Previous studies showed that vaccinated people with obesity may have lower antibody levels and remain at a higher risk of severe illness, but the reasons were unclear. Now, this new study published in the journal Nature Medicine finds that vaccinated people with obesity experience a faster decline in the ability of antibodies to fight the virus. This has important implications for how vaccines are prioritized globally.
During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID-19. In this study, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.
A team from the University of Edinburgh, led by Prof Sir Aziz Sheikh, looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID-19 in adults who received two doses of Covid-19 vaccine (either Pfizer-BioNTech BNT162b2 mRNA or AstraZeneca ChAdOx1).
The study found that those with severe obesity (BMI greater than 40 kg/m2) had a 76% higher risk of severe COVID-19 outcomes compared to those with a normal BMI. There was also a small increase in risk for those with obesity (BMI 30-39.9 kg/m2) and those who were underweight. Breakthrough infections after the second vaccine dose led to hospitalization and death sooner for those with severe obesity (around 10 weeks) and those with obesity (around 15 weeks) compared to those with a normal weight (around 20 weeks).
Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID-19 vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID-19 vaccine schedules in a post-pandemic UK.”
The University of Cambridge team, led by Dr. James Thaventhiran and Prof. Sadaf Farooqi, studied those with severe obesity at Addenbrooke’s Hospital in Cambridge. They compared the number and function of immune cells in their blood to those of those with a normal weight.
They studied people six months after their second vaccine dose and then looked at the response to a third “booster” vaccine dose over time. The Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID-19 virus as those with a normal weight.
But the ability of those antibodies to work efficiently to fight against the virus (known as ‘neutralisation capacity’) was reduced in people with obesity. 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.
“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said Dr Agatha van der Klaauw from the Wellcome-MRC Institute of Metabolic Science and first author of the paper. “We urgently need to understand how to restore immune function and minimise these health risks.”
The researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.
When given a third (booster) dose of a COVID-19 vaccine, the ability of the antibodies to neutralise the virus was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.
Dr James Thaventhiran, a Group Leader from the MRC Toxicology Unit in Cambridge and co-lead author of the SCORPIO study said: “It is promising to see that booster vaccines restore the effectiveness of antibodies for people with severe obesity, but it is concerning that their levels decrease more quickly, after just 15 weeks. This shows that the vaccines work as well in people with obesity, but the protection doesn’t last as long.”
Prof Sadaf Farooqi from the Wellcome-MRC Institute of Metabolic Science and co-lead author of the SCORPIO study said: “More frequent booster doses are likely to be needed to maintain protection against COVID-19 in people with obesity. Because of the high prevalence of obesity across the globe, this poses a major challenge for health services”.
