Comment
impacted by the pandemic.6 Additionally, there
are also concerns that the pandemic might have
a disproportionate negative effect on other aspects
of metabolic health, including provision of metabolic
surgery. Despite evidence that metabolic surgery can
reduce diabetes-related morbidity and mortality, access
to metabolic surgery has historically been undermined
compared with other elective surgery due to barriers,
including weight stigma.7
There is therefore an urgent need to restore both
routine and specialist diabetes care as quickly as possible
as part of the recovery from the pandemic to prevent
further ongoing harm.
DH has received consultancy and speaker fees from Fractyl Health and Sanofi;
FR has received consultancy and speaker fees from Medtronic, Ethicon,
Novo Nordis, and GI Dynamics. The authors have not received any funding
directly related to the subject or content of this work.
*David Hopkins, Francesco Rubino
dhopkins3@nhs.net
Impact of BMI on COVID-19 vaccine effectiveness
COVID-19 and obesity are two overlapping pandemics.1
Individuals with obesity are at risk of developing more
severe clinical outcomes as a result of SARS-CoV-2
infection than those without obesity.2,3 Obesity is also
associated with known risk factors for severe COVID-19,
such as diabetes and hypertension. Irrespective of
comorbidities, excessive weight results in biomechanical
and systemic factors that increase the risk of adverse
outcomes. Increased abdominal pressure and upward
displacement of the diaphragm result in decreased
expiratory reserve volume, functional capacity, and
respiratory system compliance. Furthermore, obesity-
associated alterations in systemic metabolism include
insulin resistance, altered adipokines (eg, increased
leptin and decreased adiponectin), and chronic
low-grade inflammation.3 Increased inflammatory
chemokines might lead to endothelial dysfunction
and exacerbate a prothrombotic state. Preliminary
research has shown that mice with obesity have an
increased duration of viral shedding due to delayed
viral clearance, increased number of secondary
bacterial infections, and heightened damage to the
respiratory epithelium.4 In addition, COVID-19 vaccine
effectiveness might be lower in people with obesity as
baseline alterations in systemic cytokine production
www.thelancet.com/diabetes-endocrinology Vol 10 August 2022 551
Department of Diabetes, School of Cardiovascular and Metabolic Medicine and
Sciences, King’s College London, London, SE5 9RS, UK (DH, FR)
1 Steenblock C, Schwarz PEH, Ludwig B, et al. COVID-19 and metabolic
disease: mechanisms and clinical management. Lancet Diabetes Endocrinol
2021; 9: 786–98.
2 Rawshani A, Kjölhede EA, Rawshani A, et al. Severe COVID-19 in people
with type 1 and type 2 diabetes in Sweden: a nationwide retrospective
cohort study. Lancet Reg Health Eur 2021; 4: 100105.
3 Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes
with COVID-19-related mortality in England: a whole-population study.
Lancet Diabetes Endocrinol 2020; 8: 813–22.
4 Mahamat-Saleh Y, Fiolet T, Rebeaud ME, et al. Diabetes, hypertension, body
mass index, smoking and COVID-19-related mortality: a systematic review
and meta-analysis of observational studies. BMJ Open 2021; 11: e052777.
5 Valbhji J, Barron E, Gorton T, et al. Associations between reductions in
routine care delivery and non-COVID-19-related mortality in people with
diabetes in England during the COVID-19 pandemic: a population-based
parallel cohort study. Lancet Diabetes Endocrinol 2022; published online
May 27. https://doi.org/10.1016/S2213-8587(22)00131-0.
6 Seidu S, Hambling C, Holmes P, et al. The impact of the COVID pandemic
on primary care diabetes services in the UK: a cross-sectional national
survey of views of health professionals delivering diabetes care.
Prim Care Diabetes 2022; 16: 257–63.
7 Rubino F, Cohen RV, Mingrone G, et al. Bariatric and metabolic surgery
during and after the COVID-19 pandemic: DSS recommendations for
management of surgical candidates and postoperative patients and
prioritisation of access to surgery. Lancet Diabetes Endocrinol 2020;
8: 640–48.
might lead to blunted and delayed innate and adaptive
immune responses to vaccination.1 Reduced vaccine
effectiveness in people with obesity has been observed
for influenza vaccination5 and preliminary results were
suggestive of lower anti-SARS-CoV-2 spike IgG antibody
concentrations after two doses of the BNT162b2 mRNA
vaccine.6
Shutterstock
To address the effect of bodyweight on vaccine
effectiveness, Carmen Piernas and colleagues7 in
The Lancet Diabetes & Endocrinology used a large
representative population-based cohort from England Published Online
June 30, 2022
of 9 171 524 individuals to investigate severe COVID-19 https://doi.org/10.1016/
outcomes after COVID-19 vaccination and associations S2213-8587(22)00170-X
with BMI. The authors applied multivariable Cox See Articles page 571
proportional hazard models to estimate the risk of
COVID-19 outcomes associated with BMI. Vaccine
protection was assessed through a nested matched
case-control design to estimate odds ratios in
vaccinated versus non-vaccinated people.
Consistent with the findings from phase 3 company-
led efficacy trials,8 the protection of COVID-19 vaccines
against severe disease outcomes was high across all BMI
categories when comparing people who were vaccinated
against those who were unvaccinated. There was
a 40–74% lower odds of hospital admission or death after
 Comment
the second dose in all BMI categories, and 90% lower odds
after the third dose.
In the vaccinated cohort, people at the two extremes
of BMI distribution (very low and very high BMI) were at
greater risk of hospitalisation or death from COVID-19
than people of healthy weight. Despite the large sample
size, the study was not powered to address variations
in vaccine effectiveness across different vaccine brands
and across circulating virus variants. The limitation of
their study design was the need to use a matched case-
control design, rather than the WHO recommended
test-negative design,9 as the cohort did not include
test-negative individuals. Another considerable
limitation in interpreting the results for the people
who had underweight include potential confounding
factors such as frailty, cachexia due to cancer, or other
conditions associated with lower BMI, which this study
did not capture. Such underlying factors for low weight
would inherently have a higher risk of severe COVID-19
outcomes than low weight itself.
There was a high vaccine uptake by people with
obesity. Conversely, people who had underweight were
less likely to be vaccinated, which might have been
an unintended result of public messaging that people
with overweight have a higher risk of severe COVID-19,
which was corroborated by the UK risk-based strategy
of vaccine rollout. These findings should prompt a shift
towards more targeted and differentiated public health
messaging to enhance vaccine uptake in people who
are underweight and who might perceive themselves at
lower risk of severe COVID-19.
The finding that vaccine effectiveness is lower in
people with higher BMI appears to be robust. Reasons
are manifold and might include poorer innate and
adaptive immune response.4 The authors postulate
that even with a good serological response there might
be an impaired T-cell response that could explain the
persistent higher risks of severe COVID-19 outcomes
Second brain tumours after pituitary irradiation: lower risk
than once thought
Published Online Since its first proposal in the treatment of pituitary
June 30, 2022
https://doi.org/10.1016/
tumours more than a century ago, indications for
S2213-8587(22)00171-1 cranial radiotherapy have notably evolved. In rare
552 www.thelancet.com/diabetes-endocrinology Vol 10 August 2022
associated with obesity despite vaccination. Vaccine
effectiveness increased with a third dose, which
underpins the need for a booster to enhance protection.
This large cohort study emphasises the crucial role of
obesity in the COVID-19 pandemic. Obesity and COVID-19
appear to be a detrimental intersection, one that has also
been observed for influenza and other infectious diseases.4
Furthermore, people with obesity in the UK have also
been affected by the pandemic lockdown measures with
increased overeating, reduced physical activity behaviour,
and increased barriers to weight management.10 Tackling
obesity as a societal problem now will help mitigate
the disastrous consequences of the current COVID-19
pandemic and those of future pandemics.
AWS serves as consultant to WHO; the opinions expressed here are those of the
author and not necessarily those of WHO. AF declares no competing interests.
*Annelies Wilder-Smith, Annika Frahsa
anneliesws@gmail.com
Institute of Social and Preventive Medicine, University of Berne, Berne, 3012,
Switzerland
1 Honce R, Schultz-Cherry S. A tale of two pandemics: obesity and COVID-19.
J Travel Med 2020; 27: taaa097.
2 Hamer M, Gale CR, Kivimaki M, Batty GD. Overweight, obesity, and risk of
hospitalization for COVID-19: a community-based cohort study of adults
in the United Kingdom. Proc Natl Acad Sci USA 2020; 117: 21011–13.
3 Popkin BM, Du S, Green WD, et al. Individuals with obesity and
COVID-19: a global perspective on the epidemiology and biological
relationships. Obes Rev 2020; 21: e13128.
4 Honce R, Schultz-Cherry S. Influenza in obese travellers: increased risk and
complications, decreased vaccine effectiveness. J Travel Med 2019; 26: taz020.
5 Neidich SD, Green WD, Rebeles J, et al. Increased risk of influenza among
vaccinated adults who are obese. Int J Obes (Lond) 2017; 41: 1324–30.
6 Yamamoto S, Mizoue T, Tanaka A, et al. Sex-associated differences between
BMI and SARS-CoV-2 antibody titers following the BNT162b2 vaccine.
Obesity (Silver Spring) 2022; 30: 999–1003.
7 Piernas C, Patone M, Astbury NM, et al. 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.
Lancet Diabetes Endocrinol 2022; published online June 30. https://doi.
org/10.1016/S2213-8587(22)00158-9.
8 Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2
mRNA COVID-19 vaccine. N Engl J Med 2020; 383: 2603–15.
9 Patel MK, Bergeri I, Bresee JS, et al. Evaluation of post-introduction
COVID-19 vaccine effectiveness: summary of interim guidance of the
World Health Organization. Vaccine 2021; 39: 4013–24.
10 Robinson E, Boyland E, Chisholm A, et al. Obesity, eating behavior and
physical activity during COVID-19 lockdown: a study of UK adults.
Appetite 2021; 156: 104853.
pituitary carcinomas, indication of radiotherapy remains
undisputable after surgical treatment in case of remnant
tumour or recurrence. Until the availability of effective