Obesity and covid-19: the unseen risks
It is remarkable that two seemingly disparate risk factors have emerged for susceptibility and severity of covid-19: obesity1 and ethnicity.2 Whilst several characteristics including socioeconomic, cultural, or lifestyle factors, genetic predisposition, or pathophysiological differences may influence susceptibility or response to COVID-19 in people from black, Asian, and minority ethnic heritage,3 it should be remarked that black adults are the most likely out of all ethnic groups to be overweight or obese.4 Furthermore, we suggest that one poorly-recognised risk factor in ethnic minority communities could be normal-weight obesity wherein individuals have excessive body fat, particularly visceral fat, despite a normal weight based on body mass index (BMI).5 In people with conventional or normal-weight obesity, insulin resistance, hyperinsulinaemia, type 2 diabetes, hypertension, hypertriglyceridaemia, atherosclerotic cardiovascular disease and higher levels of pro-inflammatory cytokines expressed in adipose tissue may augment the critical effects of covid-19.6
We also wish to draw attention to the often-overlooked matter of obesity as a cause of suboptimal treatment in infectious diseases due to its adverse influence on pharmacokinetic and pharmacodynamic properties of drugs, and their efficacy and safety. Obesity also impairs the protective immune response to virus infection and vaccination, as seen with influenza, through alterations of cellular immunity.7 8 Higher BMI is associated with greater decline in antibody titres 12 months after vaccination and impairment of CD8+ T-cell activation and functional responses to ex vivo influenza virus challenge.7 Furthermore, vaccinated adults with obesity have twice the risk of influenza despite equal serological response compared with healthy-weight adults. The reduced immune response to vaccination can be detrimental not only to the individual but also herd immunity.
Global efforts at development of therapeutics for COVID-19 have focussed on drug-repurposing, immunotherapies including convalescent plasma and monoclonal antibodies, and vaccines. Despite obesity prevalence rates of 40% in the US, 29% in England and 13% globally, none of the several thousand clinical studies of covid-19 in international clinical trial registries to our knowledge proactively recruit participants with obesity. On the contrary, several studies consider overweight and/or obesity as exclusion criteria. We call for proportional representation of people with obesity in clinical trials of drugs and vaccines, including dose-finding studies.
1. Tan M, He FJ, MacGregor GA. Obesity and covid-19: the role of the food industry. BMJ 2020 doi: 10.1136/bmj.m2237
2. Patel P, Hiam L, Sowemimo A, et al. Ethnicity and covid-19. BMJ 2020;369:m2282. doi: 10.1136/bmj.m2282
3. Khunti K, Singh AK, Pareek M, et al. Is ethnicity linked to incidence or outcomes of covid-19? BMJ 2020;369:m1548. doi: 10.1136/bmj.m1548
4. Overweight adults: Public Health England; 2020 [cited 2020 16 Jun]. Available from: https://www.ethnicity-facts-figures.service.gov.uk/health/diet-and-exerc... accessed 16 Jun 2020.
5. Franco LP, Morais CC, Cominetti C. Normal-weight obesity syndrome: diagnosis, prevalence, and clinical implications. Nutrition reviews 2016;74:558-70. doi: 10.1093/nutrit/nuw019
6. Sattar N, McInnes IB, McMurray JJV. Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation 2020 doi: 10.1161/circulationaha.120.047659
7. Sheridan PA, Paich HA, Handy J, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. International journal of obesity (2005) 2012;36:1072-7. doi: 10.1038/ijo.2011.208
8. Green WD, Beck MA. Obesity Impairs the Adaptive Immune Response to Influenza Virus. Annals of the American Thoracic Society 2017;14:S406-S09. doi: 10.1513/AnnalsATS.201706-447AW
Competing interests: No competing interests