Covid vaccines are very effective, but for some groups they do not induce a strong immune response. These groups include older adults and people with weakened immune systems, for example due to cancer or other medical conditions. They are already at high risk from Covid.
Similarly, obesity – and its association with many other conditions such as type 2 diabetes, high blood pressure and chronic kidney disease – increases the risk of severe covid.
The effect of obesity on the effectiveness of the Covid vaccine, however, is not well understood. But our new study in Nature Medicine has found that obesity is linked to a faster loss of immunity from the Covid vaccine.
We know that obese people have a weaker immune response to other vaccines, including influenza, rabies and hepatitis.
Covid vaccines generate antibodies that recognize the spike protein, a protein on the surface of SARS-CoV-2 (the virus that causes Covid) that allows it to attach to and infect our cells. Vaccines also target immune cells called T cells to protect against severe Covid if we contract the virus.
As immunity acquired after two doses declines in subsequent months, many countries have chosen to administer booster vaccines to maintain immune protection, particularly in vulnerable groups.
Several studies have suggested that after the Covid vaccine, antibody levels may be lower in people with obesity than in the general population.
At the start of the pandemic, we assembled a team of researchers from the University of Cambridge and the University of Edinburgh to investigate the impact of obesity on vaccine effectiveness over time.
Using a data platform called EAVE II, a University of Edinburgh team led by Aziz Sheikh examined real-time healthcare data from 5.4 million people across Scotland.
Specifically, they looked at hospitalizations and deaths from Covid among 3.5 million adults who received two doses of the vaccine (Pfizer or AstraZeneca).
They found that people with severe obesity, defined as a body mass index (BMI) above 40, had a 76 percent increased risk of hospitalization and death from Covid after vaccination compared to people with a BMI in the normal range. The risk was also moderately increased in those who were obese (BMI between 30 and 40) and underweight (BMI less than 18.5).
The risk of severe disease from successful infection after the second vaccination also began to increase more rapidly in severely obese people (after about ten weeks of vaccination) and in obese people (from about 15 weeks) than in people of normal weight. (from around 20 weeks).
Further investigation is underway
Our team conducted experiments to characterize the immune response to a third dose, or booster, of mRNA Covid vaccines (made by Pfizer and Moderna) in severely obese people.
We studied 28 severely obese people attending Addenbrooke’s Hospital in Cambridge, and measured the levels and function of antibodies as well as the number of immune cells in their blood after vaccination. We compared the results with 41 people of normal weight.
Even though the antibody levels were the same in all participants’ samples before the booster vaccination, the ability of the antibodies to work efficiently against the virus in people with severe obesity, known as “neutralization capacity”.
We could not detect either neutralization capacity in 55 percent of people with severe obesity, compared with 12 percent of people with normal BMI.
This means that Covid vaccines may produce lower quality antibodies in obese people. It is possible that the antibodies are not able to bind to the virus as strongly as in people of normal weight.
After a booster, antibody activity in obese individuals was restored to levels similar to those of normal weight. However, using detailed measurements of B cells responsible for antibody production and immune memory, we found that these immune cells developed differently during the first two weeks after vaccination in obese humans.
By repeating the measurement of immune responses over time, we could see that antibody levels and function dropped sharply after the third dose in people with severe obesity.
What does it mean?
Both parts of the study had some limitations. For example, BMI data were collected only once in EAVE II and therefore we cannot exclude changes in BMI over time. Also, the number of individuals included in our in-depth immunology study was relatively modest.
However, immunity to Covid vaccines does not appear to be as strong or long-lasting in obese people.
With severe obesity affecting 3 percent of the UK population and 9 percent of the US population, these findings have important implications.
First, covid boosters may be particularly important for this group. Our study also highlights the need for more targeted interventions to protect people with obesity from severe covid.
Evidence shows that a weight loss of at least 5 percent can reduce the risk of type 2 diabetes and other metabolic complications of obesity. Interventions that lead to sustained weight loss (such as lifestyle modifications, weight loss medications, and bariatric surgery) may improve covid outcomes.
Weight loss may also improve vaccine response, but we need more research to investigate.
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