Two doses of the COVID-19 vaccine are effective against severe disease for people who are underweight, overweight, or who have obesity, finds new research published in The Lancet Diabetes and Endocrinology.
Obesity was flagged as a risk factor for severe COVID-19 early in the global pandemic. The UK’s vaccine programme in 2021 gave priority to people with a BMI over 40, categorising them as a high-risk group. However, prior to this study, little was known about the effectiveness of the COVID-19 vaccines for overweight people and those with obesity.
The new study, led by researchers at the University of Oxford, also found that vaccinated people with underweight or overweight are at greater risk of hospitalisation and death compared with vaccinated people of healthy weight. This replicates the findings seen in a previous analysis before the vaccination programme began. Moreover, the findings suggest that underweight people were less likely to be vaccinated, although the reasons for this are not well understood.
This study adhered to the World Health Organisation classifications of body mass index (BMI), which are as follows: 18.5-24.9kg/m2 for healthy weight; below 18.5 for underweight; 25-29.9 for overweight; and 30 and over as obese, with levels adjusted for Asian people to reflect the higher health risks at lower BMI levels in this group. Characteristics such as age, sex, smoking status, and social deprivation were also accounted for in the analyses.
While COVID is a different illness and situation compared to seasonal flu, previous studies have indicated that people with obesity are less likely to take seasonal flu vaccines and have modestly reduced benefits from flu vaccinations. The reasons for this are not well understood, and until now, it was unknown if the same applied to COVID-19.
This study, made up of over nine million people across the UK, provides some of the first indicators as to the effectiveness of COVID-19 vaccines across BMI categories. Further research is required before these questions may be confidently answered.
Lead author Dr Carmen Piernas of the University of Oxford’s Nuffield Department of Primary Care Health Sciences says of the study’s encouraging results: 'Our findings provide further evidence that COVID-19 vaccines save lives for people of all sizes. Our results provide reassurance to people living with obesity that COVID-19 vaccines are equally as effective for them as for people with a lower BMI, and that vaccination substantially lowers their risk of severe illness if they are infected with COVID-19.'
Dr Piernas adds: 'These data also highlight the need for targeted efforts to increase vaccine uptake in people with a low BMI, where uptake is currently lower than for people with a higher BMI.'
Dr Piernas and her team meticulously searched anonymised health records from more than 12 million patients across 1,738 GP practices in England taking part in QResearch – a secure database of healthcare information available to verified researchers. Of these, 9,171,524 patients who were over 18 years old, had BMI data, and had not previously been infected with SARS-CoV-2 were included in the study.
Of over nine million people included in the study, 566,461 tested positive for SARS-CoV-2 during the study period, from 8th December 2020 (date of the first vaccine given in the UK) to 17th November 2021. Of those, 32,808 were admitted to hospital and 14,389 died.
The proportion of people who had had no doses of any COVID-19 vaccine at the end of the study were 23.3% of the healthy weight group (817,741 of 3,509,231 people), 32.6% of the underweight group (104,488 of 320,737 people), 16.8% of the overweight group (513,570 of 3,062,925 people) and 14.2% of the obese group (322,890 of 2,278,649 people).
To best gauge vaccine effectiveness, the risk of severe disease in vaccinated versus non-vaccinated people was compared at least 14 days after a second dose. The researchers found that being vaccinated offered high protection across all BMI groups, but that the effect was slightly lower in underweight people. Being underweight and vaccinated reduced the likelihood of being hospitalised by about a half or dying compared with being unvaccinated and underweight.
However, for all groups other than people underweight, being vaccinated meant people were around 70% less likely to be hospitalised than unvaccinated people Moreover, these groups were also around two-thirds less likely to die than their unvaccinated counterparts two weeks after a second dose.
Looking only at vaccinated people, even though vaccination helped reduce the number of severe COVID-19, there was a significantly higher risk of severe disease for people underweight, overweight or with obesity compared to people with a healthy BMI following two doses of vaccine. For example, a BMI of 17 was linked to a 50% increase in risk of hospitalisation compared with a healthy BMI of 23, and a very high BMI of 44 had three times the risk of hospitalisation compared with a healthy BMI. This is similar to the increased risk of severe COVID-19 outcomes shown prior to the vaccination programme.
Dr Piernas says: 'The cause of the increased risk among people with obesity is unknown. It is, however, consistent with the higher rate of seasonal flu infections in people with a higher BMI. We suspect that these findings may be explained, in part, by an altered immune response in heavier weight individuals, but that is just speculation at this point. The reduced effectiveness of COVID-19 vaccines among people with a low BMI may also reflect a reduced immune response due to frailty or other conditions associated with low body weight. Further research is needed to explore the relationship between BMI and immune responses.'
The authors note several limitations to their study, notably that some measurements of BMI were based on self-report, or on data recorded in GP records before the study onset that could be outdated. Additionally, the effects of booster jabs could not be investigated due to the limited numbers of people who had had three doses by the study close. Finally, data did not allow for researchers to investigate between Pfizer, AstraZeneca or Moderna vaccines, nor virus variants.
The authors conclude by stating that policy makers should continue to emphasise the importance of vaccination to people of all BMI groups.
The full paper, 'Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study', can be read in The Lancet Diabetes and Endocrinology.
This study was supported by Health Data Research UK (HDRUK) in partnership with the Office for National Statistics and funded by UK Research and Innovation. It was also supported by the NIHR Oxford Biomedical Research Centre (BRC) and the NIHR Oxford and Thames Valley Applied Research Collaboration. It was conducted by researchers from the University of Oxford, UK; Oxford University Hospitals NHS Foundation Trust; the University of Edinburgh, UK; the University of Leicester, UK and the University of Nottingham, UK, full list at the end of the Article.