Obesity undermines COVID-19 vaccines

By Neha MathurReviewed by Benedette Cuffari, M.Sc.May 15 2023

In a recent article published in the journal Nature Medicine, researchers compare the effectiveness of coronavirus disease 2019 (COVID-19) vaccines between obese and individuals with a normal body mass index (BMI) ranging between 18.5 and 24.9 kg/m².

Study: Accelerated waning of the humoral response to COVID-19 vaccines in obesity. Image Credit: SUPERMAO / Shutterstock.com

Background

Current estimates indicate that 3% of the United Kingdom and 9% of the United States population is considered obese. Obesity can increase the risk of developing many comorbidities, such as type II diabetes (T2D) and chronic kidney diseases.

During the COVID-19 pandemic, severe obesity was identified as a critical risk factor for developing severe COVID-19. Since COVID-19 vaccines reduce the risk of serious COVID-19, there is an urgent need to assess the effects of obesity on responses to messenger ribonucleic acid (mRNA) and adenoviral vector vaccines.

Several studies have suggested that obesity impairs immune responses to many vaccines, such as rabies, influenza, and hepatitis vaccines. In fact, some studies have shown that COVID-19 vaccines elicit lower antibody titers in obese people as compared to the general population, thus makes these individuals high-risk to severe COVID-19.

About the study

In this study, researchers investigate the durability of protection conferred by COVID-19 vaccination in obese individuals. To this end, fully vaccinated obese adults 18 years or older were identified from Scotland's Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. This study cohort received at least two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccines between December 8, 2020 and March 19, 2022.

About 500,000 people were obese, 98,000 of whom were severely obese with BMI of over 40 kg/m² and experienced severe COVID-19 outcomes. The second study cohort comprised 41 and 16 individuals with normal BMI who were evaluated six months after the primary vaccination series and after the third-dose vaccination, respectively.

The EAVE II platform allowed the researchers to examine the impact of the study participants’ clinical and sociodemographic characteristics, including COVID-19 history, time elapsed since receipt of the second and third vaccine doses, and dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant at the time of vaccination.

For most individuals, BMI measurements were available in their the primary care record. If missing, the researchers calculated BMI data using an average of 10 least squares regressions with all other independent variables covered as predictors.

The frequency and rate for every 1,000 person-years of severe COVID-19 outcomes were determined. The association between sociodemographic and clinical factors and study outcomes as rate ratios (RRs) with 95% confidence intervals (CIs) was also determined using generalized linear models (GLMs). Adjusted RRs (aRRs) were also obtained after adjusting for all confounders like gender and sex.

Results

In this study, the researchers prospectively measured temporally-varying humoral immune responses elicited against the authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in vaccinated individuals with severe obesity and normal BMI.

People with higher BMI, including those who were considered obese and severely obese, were at an increased risk of severe COVID-19, including hospitalization and mortality. Severely obese individuals also had fewer neutralizing antibody titers six months after primary vaccination than those with a normal BMI.

The altered antibody kinetics reflect the reduced affinity or dissociation between anti-receptor binding domain (RBD) antibodies and neutralizing potential, which has been previously observed in severe COVID-19 patients in other settings, such as after influenza vaccination.

However, peak antibody levels were higher in severely obese individuals than those with a normal BMI. Thus, vaccine delivery did not fail in obese individuals due to short needle length, which implies that a fixed dosing schedule is more appropriate for COVID-19 vaccination of all individuals, including severely obese people.

Conclusions

The study findings demonstrated that COVID-19 vaccines do not fail to target neutralizing spike epitopes in people with severe obesity. Instead, the lack of high-affinity antibodies is associated with the relative reduction in the neutralizing capacity of vaccine-induced antibodies.

There is growing evidence that weight loss of even 5% could reduce the risk of many metabolic complications arising from diseases like T2D that often affect obese individuals. Thus, lifestyle modifications and interventions like bariatric surgery that help achieve weight loss could similarly mitigate COVID-19 outcomes. 

Further studies should determine whether hyperglycemia modulates the risk of poor COVID-19 outcomes in people with severe obesity. Additional research is also needed to investigate whether weight loss has beneficial effects on COVID-19 vaccine-elicited humoral immunity.

Although it may be challenging for healthcare providers to implement vaccine programs, administering additional booster doses more frequently in obese individuals who rapidly lose vaccine-elicited humoral responses over time could help this high-risk population achieve durable protection against severe COVID-19.