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Obesity Accelerates Loss of COVID-19 Vaccination Immunity

Obesity has been linked with a faster decline in protection from vaccination, according to a new study led by the Universities of Cambridge and Edinburgh.

Early on in the COVID-19 pandemic, obesity was associated with an increased risk of severe coronavirus infection, including a higher risk of hospitalisation and increased mortality. Researchers of the new study, published in Nature Medicine, said that previous reports had suggested that COVID-19 post-vaccination antibody levels may be lower in obese people, and that people with obesity may be at higher risk of severe disease than those vaccinated and of healthy weight. The reasons for this had, however, remained unclear.

The team set out to investigate the degree of protection offered by the Pfizer-BioNTech (BNT162b2 mRNA) and AstraZeneca (ChAdOx1) vaccines in people with obesity, compared with those with a healthy weight. They used data from the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study, a surveillance platform that tracked the health of almost 3.6 million people in the Scottish population in real-time.

They extracted data from EAVE II to assess the relationship between body mass index (BMI) and coronavirus hospitalisation and mortality in adults who had received two doses of one or other COVID-19 vaccines. The cohort included over half a million vaccinated individuals with obesity and more than 98,000 vaccinated individuals with severe obesity.

Obese People had Higher Rates of Hospitalisation and Death

The new study reported that "vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalisation or death from COVID-19 – adjusted rate ratio of 1.76". 

A modest increase in risk was also seen in people with obesity (30.0 to 39.9 kg/m2) – a level that affects a quarter of the UK population, the team pointed out – as well as in people who were underweight. 

'Break-through infections' after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with a healthy weight (after 20 weeks).

The team then conducted a prospective longitudinal study of a small cohort of 28 individuals with severe obesity attending Addenbrooke's Hospital in Cambridge, and compared them with 41 people with a healthy BMI (BMI 18.5 to 24.9 kg/m2). This study – SARS-CoV2 Vaccination Response in Obesity (SCORPIO) – found that 6 months after a second vaccine dose, 55% of individuals with severe obesity had unquantifiable titres of neutralising antibody against SARS-CoV-2, compared with 12% of individuals with a healthy BMI (P=0.0003) 

Obese People May Need More Frequent Boosters

In addition, at any given anti-spike and anti-receptor-binding domain antibody level, neutralising capacity among people with severe obesity was lower than that of those with a healthy BMI. Neutralising capacity in the severely obese was restored by a third dose of vaccine, but again declined more rapidly thereafter.

"Waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity" the researchers concluded. They suggested that obese people were likely to need more frequent booster doses to maintain immunity, and that their findings had "important implications for vaccine prioritisation policies".

Lead researcher Aziz Sheikh, professor of primary care research and development at the University of Edinburgh, 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." The findings "generate important and timely insights" that should enable improvements to the delivery of COVID-19 vaccines, he said.

First author Dr Agatha van der Klaauw, clinical lecturer in metabolic medicine at the Wellcome-MRC Institute of Metabolic Science in Cambridge, said: "This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection.

"We urgently need to understand how to restore immune function and minimise these health risks."

Co-lead author of the SCORPIO study I Sadaf Farooqi, professor of metabolism and medicine at the Wellcome-MRC Institute, 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."

EAVE II is funded by the Medical Research Council with the support of BREATHE – The Health Data Research Hub for Respiratory Health, which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation and National Core Studies-Immunity. Additional support was provided through Public Health Scotland, the Scottish Government Director-General Health and Social Care and the University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research Health Technology Assessment program.

AS is a member of the Scottish Government's Standing Committee on Pandemic Preparedness and the Risk Stratification Subgroup of the UK Government’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG). He was a member of AstraZeneca's Thrombotic Thrombocytopenic Task Force. All roles are unremunerated. SJD is a scientific advisor to the Scottish Parliament on COVID-19, for which she receives a fee. ISF has consulted for Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals on weight loss drugs. All other authors have no conflicts of interest to declare.