In a recent study posted to the medRxiv* pre-print server, researchers examined a clinical cohort of severely obese people vaccinated with coronavirus disease 2019 (COVID-19) vaccines to determine the relationship between an individual’s body mass index (BMI) and COVID-19-related hospitalization and mortality. They demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced humoral immunity waned more quickly in people with severe obesity.
Study: Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity. Image Credit: Suzanne Tucker / Shutterstock
Studies have demonstrated the impact of obesity on the increased risk of developing severe COVID-19 and how obese people exhibit impaired immune responses to vaccines against other pathogenic infections, including influenza, rabies, and hepatitis. However, few studies have investigated the efficacy of anti-SARS-CoV-2 vaccines or the waning of vaccine-induced immune responses in obese people.
About the study
In the present study, researchers used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform to collect healthcare data for 5.4 million individuals in Scotland, United Kingdom. They made two study cohorts comprised of 41 normal-weight people and 28 severely obese people and performed longitudinal immunophenotyping.
The team filtered data of 3,522,331 adults who had received a second or third dose of a COVID-19 vaccine. They examined the impact of BMI on COVID-19-related hospitalization and mortality starting 14 days after receiving the second dose of either the BNT162b2 or ChAdOx1 nCoV-19 vaccine. The team recorded BMI for 49.2% of the screened individuals in total.
The researchers followed up on these individuals until hospitalization, death, or the culmination of the study. They also investigated the specific impairment in humoral immunity associated with severe obesity using high dimensional spectral flow cytometry, which enumerated and phenotyped SARS-CoV-2 receptor-binding domain (RBD) and spike (S)- binding B cells. Lastly, they performed an interaction test to evaluate whether vaccine effectiveness differed over time in people with severe obesity.
Between September 2020 and March 2022, 0.3% of the screened study participants, i.e., 10,983 people, had severe COVID-19, of which 9,733 and 2,207 individuals were hospitalized and died due to COVID-19, respectively. Although the levels of anti-S and anti-RBD immunoglobulin G (IgG) antibodies were similar in people with severe obesity and normal-weight people, these antibodies neutralized SARS-CoV-2 at a much-reduced rate in people with severe obesity. Further, vaccinated people with BMI over 40 kg/m2 were more likely to experience COVID-19-related hospitalization or death, and the risk increased over the time since vaccination. Accordingly, they had an adjusted rate ratio (aRR) of 1.76 after adjusting for age, gender, and socioeconomic status.
Furthermore, six months after the second vaccination, severely obese people had undetectable neutralizing antibody titers against SARS-CoV-2. In addition, they had decreased frequencies of antigen-experienced SARS-CoV-2 S-binding B cells and a clear dissociation between the magnitude of antibodies and their neutralizing potential. Furthermore, the study data suggested that the extrafollicular pathway of anti-SARS-CoV-2 neutralizing antibody production induced after vaccination was preferred in obese people, whereas the germinal center (GC) pathway was not. Consequently, they did not have memory B cells and long-lived antibody-secreting plasma cells that could persist and confer long-term immune protection.
The interaction test results indicated vaccine effectiveness differed across BMI groups, with more rapid waning in those with increased BMI. Although the booster dose restored the anti-SARS-CoV-2 neutralizing antibody titers in people with severe obesity, the titers again declined more quickly in obese people compared to people with normal weight. Regardless of vaccination, people with type 2 diabetes were independently associated with an increased risk of a severe COVID-19, aaR=1.13; however, the risk was much less than that associated with severe obesity. After adjusting for BMI, the aRR for type 2 diabetes was reduced to 1.06.
In summary, the results of this study suggested that severe obesity impaired the maintenance of humoral immunity following the vaccination against SARS-CoV-2, increasing the risk of severe disease progression. As obesity is highly prevalent worldwide, the study findings have serious public health implications. The authors, therefore, emphasized the need to acknowledge the severely obese as a high-risk group and prioritize them for additional or more frequent booster doses to maintain protection against breakthrough infections from emerging SARS-CoV-2 variants.
Moreover, further studies should determine how hyperglycemia modulates the risk associated with severe obesity. Likewise, further research is warranted to explore the mechanisms by which obesity affects the response to immunological challenges such as vaccination to devise ways to reduce such effects.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity, Agatha A. van der Klaauw MD, PhD, Emily C. Horner BSc, Pehuen Pereyra-Gerber PhD, Utkarsh Agrawal PhD, William S. Foster BSc, MRes,, Sarah Spencer MD, BSc, Bensi Vergese BSc Hons., Miriam E. Smith BSc PhD, Elana Henning B.Soc.Sc, Isobel D. Ramsay MA BM BCh, Jack A. Smith BSc MBiol, Stephane M. Guillaume BSc, Hayley J. Sharpe BSc, PhD, Iain M. Hay BSc, PhD, Sam Thompson BSc, Silvia Innocentin BSc., Ph.D, Lucy H Booth BSc, Chris Robertson Ph.D., Colin McCowan Ph.D., Thomas E Mulroney PhD, Martin J O’Reilly, Thevinya P Guragama, Lihinya P Guragama, Maria A Rust BSc, Alex Ferreira, Soraya Ebrahimi MSc, Lourdes Ceron-Gutierrez MSc., Jacopo Scotucci MD, Barbara Kronsteiner Ph.D., Susanna J. Dunachie MD., Ph.D., Paul Klenerman MD., Ph.D., PITCH Consortium, Adrian J. Park MD PhD, Francesco Rubino MD.,, Hannah Stark BSc, Nathalie Kingson PhD, Rainer Doffinger PhD, Michelle A. Linterman BBmedSc (H, Nicholas J. Matheson MA BM BCh, Aziz Sheikh MD, I. Sadaf Farooqi MD, PhD, James E. Thaventhiran MD, PhD, medRxiv pre-print 2022, DOI: https://doi.org/10.1101/2022.06.09.22276196, https://www.medrxiv.org/content/10.1101/2022.06.09.22276196v1