Associations of body mass index with COVID-19 vaccine uptake, vaccine effectiveness and risk of severe COVID-19 outcomes after vaccination: a population-based cohort of 9 million people in England

BACKGROUND: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England.METHODS: In this population-based cohort study, we used the QResearch database of general practice records and included patients aged 18 years or older who were registered at a practice that was part of the database in England between Dec 8, 2020 (date of the first vaccination in the UK), to Nov 17, 2021, with available data on BMI. Uptake was calculated as the proportion of people with zero, one, two, or three doses of the vaccine across BMI categories. Effectiveness was assessed through a nested matched case-control design to estimate odds ratios (OR) for severe COVID-19 outcomes (ie, admission to hospital or death) in people who had been vaccinated versus those who had not, considering vaccine dose and time periods since vaccination. Vaccine effectiveness against infection with SARS-CoV-2 was also investigated. Multivariable Cox proportional hazard models estimated the risk of severe COVID-19 outcomes associated with BMI (reference BMI 23 kg/m 2) after vaccination. FINDINGS: Among 9 171 524 participants (mean age 52 [SD 19] years; BMI 26·7 [5·6] kg/m 2), 566 461 tested positive for SARS-CoV-2 during follow-up, of whom 32 808 were admitted to hospital and 14 389 died. Of the total study sample, 19·2% (1 758 689) were unvaccinated, 3·1% (287 246) had one vaccine dose, 52·6% (4 828 327) had two doses, and 25·0% (2 297 262) had three doses. In people aged 40 years and older, uptake of two or three vaccine doses was more than 80% among people with overweight or obesity, which was slightly lower in people with underweight (70-83%). Although significant heterogeneity was found across BMI groups, protection against severe COVID-19 disease (comparing people who were vaccinated vs those who were not) was high after 14 days or more from the second dose for hospital admission (underweight: OR 0·51 [95% CI 0·41-0·63]; healthy weight: 0·34 [0·32-0·36]; overweight: 0·32 [0·30-0·34]; and obesity: 0·32 [0·30-0·34]) and death (underweight: 0·60 [0·36-0·98]; healthy weight: 0·39 [0·33-0·47]; overweight: 0·30 [0·25-0·35]; and obesity: 0·26 [0·22-0·30]). In the vaccinated cohort, there were significant linear associations between BMI and COVID-19 hospitalisation and death after the first dose, and J-shaped associations after the second dose. INTERPRETATION: Using BMI categories, there is evidence of protection against severe COVID-19 in people with overweight or obesity who have been vaccinated, which was of a similar magnitude to that of people of healthy weight. Vaccine effectiveness was slightly lower in people with underweight, in whom vaccine uptake was also the lowest for all ages. In the vaccinated cohort, there were increased risks of severe COVID-19 outcomes for people with underweight or obesity compared with the vaccinated population with a healthy weight. These results suggest the need for targeted efforts to increase uptake in people with low BMI (FUNDING: UK Research and Innovation and National Institute for Health Research Oxford Biomedical Research Centre.