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/m²) 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/m²). 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.

肥胖与严重的 2019 年冠状病毒病 (COVID-19) 感染和死亡风险增加有关。COVID-19 疫苗可降低 COVID-19 严重后果的风险；然而，它们对肥胖患者的有效性尚不完全清楚。我们使用 COVID-19 早期大流行评估和加强监测 (EAVE II) 监测平台研究了苏格兰 360 万人的体重指数 (BMI)、住院率和 COVID-19 死亡率之间的关系。我们发现接种疫苗的个体患有严重肥胖症（BMI > 40 kg/m ²) 因 COVID-19 而住院或死亡的可能性增加 76%（调整后比率为 1.76（95% 置信区间 (CI)，1.60–1.94））。我们还对一组 28 名重症患者进行了前瞻性纵向研究肥胖与 41 名 BMI 正常（BMI 18.5–24.9 kg/m ²）的对照个体进行比较。我们发现，55% 的重度肥胖个体具有无法量化的针对真实严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的中和抗体滴度) 病毒，而 12% 的 BMI 正常者 ( P = 0.0003) 第二次接种疫苗后 6 个月。此外，我们观察到，对于严重肥胖的个体，在任何给定的抗尖峰和抗受体结合域 (RBD) 抗体水平下，中和能力都低于 BMI 正常的个体。中和能力通过第三剂疫苗恢复，但在重度肥胖人群中再次下降得更快。我们证明，在严重肥胖的个体中，COVID-19 疫苗诱导的体液免疫力的减弱会加速。由于肥胖与突破性感染的住院率和死亡率增加有关，因此我们的研究结果对疫苗优先排序政策有影响。