Accelerated waning of the humoral response to COVID-19 vaccines in obesity

van der Klaauw, Agatha A. and Horner, Emily C. and Pereyra-Gerber, Pehuén and Agrawal, Utkarsh and Foster, William S. and Spencer, Sarah and Vergese, Bensi and Smith, Miriam and Henning, Elana and Ramsay, Isobel D. and Smith, Jack A. and Guillaume, Stephane M. and Sharpe, Hayley J. and Hay, Iain M. and Thompson, Sam and Innocentin, Silvia and Booth, Lucy H. and Robertson, Chris and McCowan, Colin and Kerr, Steven and Mulroney, Thomas E. and O’Reilly, Martin J. and Gurugama, Thevinya P. and Gurugama, Lihinya P. and Rust, Maria A. and Ferreira, Alex and Ebrahimi, Soraya and Ceron-Gutierrez, Lourdes and Scotucci, Jacopo and Kronsteiner, Barbara and Dunachie, Susanna J. and Klenerman, Paul and Park, Adrian J. and Rubino, Francesco and Lamikanra, Abigail A. and Stark, Hannah and Kingston, Nathalie and Estcourt, Lise and Harvala, Heli and Roberts, David J. and Doffinger, Rainer and Linterman, Michelle A. and Matheson, Nicholas J. and Sheikh, Aziz and Farooqi, I. Sadaf and Thaventhiran, James E. D. (2023) Accelerated waning of the humoral response to COVID-19 vaccines in obesity. Nature Medicine, 29 (5). pp. 1146-1154. ISSN 1078-8956 (

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Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m ) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60-1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5-24.9 kg/m ). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies.