Table 1.

Policy summary

Background	Obesity is associated with increased hospitalization and mortality due to severe COVID-19. Although COVID-19 vaccines are highly effective, details of the immune response and duration of vaccine efficacy in individuals with obesity are unknown.
Main findings and limitations	Using real-time data collected on over 3.6 million people in Scotland who had received two doses of primary COVID-19 vaccine, we show that the risk of severe COVID-19 is markedly increased (76%) in individuals with severe obesity (BMI > 40 kg/m2). Breakthrough infections resulted in increased hospitalization and mortality due to COVID-19 and occurred more rapidly in individuals with severe obesity than in individuals with normal weight (after 10 weeks versus after 20 weeks), suggesting more rapid waning of protection. In an accompanying clinical study, we show that peak neutralizing antibody titers are similar in individuals with normal weight and individuals with severe obesity, indicating that the initial vaccine response is similar between the two groups. However, longitudinal immunophenotyping of both groups demonstrated that neutralizing capacity declines more rapidly in individuals with severe obesity. Although we did not observe an associated T cell defect, the number of individuals studied in the clinical cohort was modest, limiting the power to detect small differences.
Policy implications	Taken together, our results indicate that increased BMI affects the rate of decline of vaccine-mediated immunity against SARS-CoV-2 in the population. Given the high prevalence of obesity worldwide, these findings have major implications for vaccination policy globally. COVID-19 vaccines may need to be administered more frequently in individuals with severe obesity to achieve the duration of protection from severe COVID-19 that is seen in individuals with normal BMI. Furthermore, our demonstration that the kinetics of the adaptive immune response to vaccination differs in individuals with severe obesity has implications for immunization against other infectious diseases where the longitudinal vaccine response remains incompletely characterized. There is a pressing need to ensure appropriate demographic representation in clinical research studies and trials, which must seek to include individuals with varying degrees of obesity. Our work highlights the critical importance of collecting data on BMI and metabolic risk factors so that lessons can be learned rapidly to guide changes in policy and improve health outcomes.