Obesity accelerates loss of immunity from COVID vaccines, new research finds

COVID vaccines are very effective but do not elicit as strong an immune response in some groups.

These groups include older adults and people with weakened immune systems, for example due to cancer or other diseases. They tend to already be at increased risk from COVID.

Likewise, obesity – and its association with several other conditions such as type 2 diabetes, high blood pressure and chronic kidney disease – leads to an increased risk of severe COVID.

However, the impact of obesity on the effectiveness of the COVID vaccine is not fully understood. However, our new study in Nature Medicine concludes that obesity is linked to faster loss of immunity from COVID vaccines.

We know that people with obesity have an impaired immune response to other vaccines, including influenza, rabies and hepatitis vaccines.

COVID vaccines create antibodies that recognize 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.

The vaccines also stimulate immune cells called T-cells to protect against severe COVID should we contract the virus.

As the immunity acquired after two doses wanes in the months that follow, many countries have opted to administer booster vaccines to maintain immunity, particularly in vulnerable groups.

Several studies suggest that antibody levels after a COVID vaccination might 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 study the impact of obesity on the effectiveness of the vaccine over time.

Using a data platform called EAVE II, the University of Edinburgh team, led by Aziz Sheikh, examined real-time health data from 5.4 million people across Scotland.

Specifically, they looked at hospitalizations and deaths from COVID among 3.5 million adults who had received two doses of vaccine (either Pfizer or AstraZeneca).

They found that people with severe obesity, defined as a body mass index (BMI) over 40, had a 76% increased risk of hospitalization and death from COVID after vaccination compared to people with a BMI in the normal range had.

The risk was also moderately increased in people who were obese (BMI between 30 and 40) and underweight (BMI below 18.5).

The risk of serious illness from breakthrough infections after the second vaccination also began to increase faster in people with severe obesity (from around 10 weeks after vaccination) and in people with obesity (from around 15 weeks) than in people of normal weight (from around 10 weeks). 20 weeks).

Further research

Our team performed experiments to characterize the immune response to a third dose or booster dose of the mRNA-COVID vaccines (from Pfizer and Moderna) in people with severe obesity.

We looked at 28 people with severe obesity who attended Addenbrooke’s Hospital in Cambridge and measured antibody levels and function and the number of immune cells in their blood after vaccination.

We compared the results with those of 41 normal-weight people.

Although antibody levels were similar in all participants’ pre-booster samples, the ability of antibodies to fight the virus efficiently, known as “neutralizing capacity,” was reduced in people with severe obesity.

In 55% of people with severe obesity, we were unable to either assess or quantify neutralizing ability, compared to 12% of people with normal BMI.

This could mean that COVID vaccines induce lower quality antibodies in people with obesity. The antibodies may not be able to bind to the virus with the same strength as in people of normal weight.

After a booster shot, obese people returned to the same levels of antibody function as normal-weight people.

However, using detailed measurements of B cells responsible for antibody production and immune memory, we found that these immune cells developed differently in people with obesity in the first few weeks after vaccination.

By repeatedly measuring immune responses over time, we found that antibody levels and function declined more rapidly in people with severe obesity after the third dose.

What does that mean?

There were some limitations in both parts of the study. For example, BMI data in EAVE II was collected only once and therefore we cannot rule out changes in BMI over time.

In addition, the number of subjects included in our detailed immunology study was relatively modest.

Still, immunity to COVID vaccines does not appear to be as robust and long-lasting in people with obesity.

With severe obesity affecting 3% of the UK population and 9% of the US population, these findings have important implications.

First, COVID boosters could be particularly important for this group. Our study also highlights the need for more targeted interventions to protect people with obesity from severe COVID.

There is evidence that weight loss of at least 5% can reduce the risk of type 2 diabetes and other metabolic complications of obesity.

Interventions that can lead to sustained weight loss (e.g., lifestyle changes, weight-loss drugs, and bariatric surgery) could also improve COVID outcomes.

Weight loss can also improve vaccine responses, but more research is needed to investigate this.

Written by Agatha A. van der Klaauw, I. Sadaf Farooqi, James ED Thaventhiran. The conversation.

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