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Observational Study
. 2022 May;46(5):943-950.
doi: 10.1038/s41366-021-01054-3. Epub 2022 Jan 14.

Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe COVID-19 outcomes: observational study and Mendelian randomisation analysis

Min Gao #  1   2 , Qin Wang #  3 , Carmen Piernas #  4 , Nerys M Astbury  4   5 , Susan A Jebb  4   5 , Michael V Holmes  5   3   6 , Paul Aveyard  7   8
Affiliations
Observational Study

Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe COVID-19 outcomes: observational study and Mendelian randomisation analysis

Min Gao et al. Int J Obes (Lond). 2022 May.

Abstract

Background: Higher body mass index (BMI) and metabolic consequences of excess weight are associated with increased risk of severe COVID-19, though their mediating pathway is unclear.

Methods: A prospective cohort study included 435,504 UK Biobank participants. A two-sample Mendelian randomisation (MR) study used the COVID-19 Host Genetics Initiative in 1.6 million participants. We examined associations of total adiposity, body composition, fat distribution and metabolic consequences of excess weight, particularly type 2 diabetes, with incidence and severity of COVID-19, assessed by test positivity, hospital admission, intensive care unit (ICU) admission and death.

Results: BMI and body fat were associated with COVID-19 in the observational and MR analyses but muscle mass was not. The observational study suggested the association with central fat distribution was stronger than for BMI, but there was little evidence from the MR analyses than this was causal. There was evidence that strong associations of metabolic consequences with COVID-19 outcomes in observational but not MR analyses. Type 2 diabetes was strongly associated with COVID-19 in observational but not MR analyses. In adjusted models, the observational analysis showed that the association of BMI with COVID-19 diminished, while central fat distribution and metabolic consequences of excess weight remained strongly associated. In contrast, MR showed the reverse, with only BMI retaining a direct effect on COVID-19.

Conclusions: Excess total adiposity is probably casually associated with severe COVID-19. Mendelian randomisation data do not support causality for the observed associations of central fat distribution or metabolic consequences of excess adiposity with COVID-19.

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Conflict of interest statement

PA and SAJ are investigators on a trial of total diet replacement funded by Cambridge Weight Plan. PA spoke at a symposium at the Royal College of General Practitioners conference funded by Novo Nordisk. Both these activities resulted in payments to the University of Oxford but not to the investigators.

Figures

Fig. 1
Fig. 1. The MR association between adiposity traits and COVID-19 outcomes.
Note: definitions of cases and controls for COVID-19 GWAS data are in Supplementary material 1.
Fig. 2
Fig. 2. Univariable and multivariable MR associations of BMI, WHR, type 2 diabetes with COVID-19 outcomes.
MR associations of A BMI and WHR (univariable and multivariable) and B BMI and type 2 diabetes (univariable and multivariable) with COVID-19 test (1) and hospital admission (2) in multivariable MR. Note: For quantitative traits, the units are OR per SD; for binary traits, the units are OR per log(OR).
See this image and copyright information in PMC

Comment in

  • Warum Adipöse so Covid-anfällig sind.
    Wirth A. Wirth A. MMW Fortschr Med. 2022 Nov;164(19):28-29. doi: 10.1007/s15006-022-2053-y. MMW Fortschr Med. 2022. PMID: 36310267 Free PMC article. Review. German. No abstract available.

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