key: cord-0957512-ahh07u2i
authors: Deschasaux‐Tanguy, Mélanie; Bourhis, Laurent; de Lamballerie, Xavier; Carrat, Fabrice; Touvier, Mathilde
title: Body weight, body composition and the risk of SARS‐CoV‐2 infection in a large population‐based sample
date: 2021-08-01
journal: J Intern Med
DOI: 10.1111/joim.13364
sha: 53000057476132d123164010f02262c01fc1e788
doc_id: 957512
cord_uid: ahh07u2i

nan

Dear Editor, Obesity has been identified as an important risk factor for COVID-19 severity [1] . Besides, several reports also suggested that obesity (or higher BMI) may also be associated with a higher susceptibility to SARS-CoV-2 infection [1, 2] although this remains unclear. Going beyond BMI, this research letter provides insights into the associations between several anthropometric characteristics and the risk of SARS-CoV-2 infection, using exhaustive seroprevalence data acquired in a large population-based sample.

NutriNet-Santé is a French web-based cohort launched in 2009 [3] (#NCT03335644; ethical authorizations available at https://info. etude-nutrinet-sante.fr/node/12). At baseline and every 6-12 months, participants receive questionnaires based on socioeconomic status, lifestyle, physical activity and health. A subset of participants also underwent body composition measurements (BC-418MA, TANITA; 2011-2014). In April 2020, a questionnaire investigated a wide range of aspects related to the COVID-19 crisis (SAPRIS-SERO project [4] ), including bodyweight just before the March 2020 lockdown. In June 2020, self-reported measures of current waist and hip circumference were provided following detailed instructions. Participants involved in the SAPRIS-SERO project returned self-sampled dried-blood spots in May-October 2020 that were analysed to detect anti-SARS-CoV-2 antibodies directed against the spike protein (ELISA-S) and the nucleocapsid protein (ELISA-NP), as well as neutralizing antibodies (SN) [5] . More details regarding the tests are provided in Supporting Information. The main outcome was a positive ELISA-S test while being positive to all three ELISA-S, ELISA-NP and SN tests (likely to reflect more symptomatic forms of SARS-CoV-2 infection [5] ) constituted the secondary outcome. Associations between the seroprevalence of SARS-CoV-2 and anthropometric characteristics were assessed using multi-adjusted logistic regression models (twosided tests, p < 0.05 considered as statistically significant; SAS 9.4).

The main analyses included 1027 ELISA-S-positive (among which 2.6% declared a COVID-19-related hospitalization) and 20,349 ELISA-S-negative participants (flowchart in Supporting Information, characteristics of the participants in Supporting Information Table S1 ). A positive yet unclear association was observed between BMI before the March 2020 lockdown (self-reported in April 2020) and SARS-CoV-2 seroprevalence in women: a positive linear trend for ELISA-S (p 1-SD-increment = 0.07) significant when using restricted cubic splines (p = 0.04, with no evidence of non-linearity, p non-linearity = 0.1, Supporting Information Fig. S1 ) and for ELISA-S-NP/SN (p 1-SD-increment = 0.02), but no association with standard categories of BMI. No association was observed in men ( Fig. 1) . Waist circumference (p = 0.04) and waist-to-hip ratio (p = 0.01; self-reported in June 2020) were associated with a higher seroprevalence in women while opposite trends were observed in men (p = 0.08 and 0.03, respectively; restricted cubic splines in Supporting Information Fig. S2 ). Body, trunk and visceral fat (all p < 0.05) but not lean or muscle mass (measured in 2011-2014), associated with higher seroprevalence, with similar trends in women only. Overall, results were similar considering the positivity to all three ELISA-S-NP/SN tests, with yet some loss of significance following a reduced number of cases (Supporting Information Table S2 ).

Our results suggest a higher susceptibility to SARS-CoV-2 infection in women with higher body fat, displaying a moderate association with BMI, consistent with some prior reports [1, 2] , but clearer associations with more specific markers of central adiposity. The higher risk of SARS-CoV-2 infection associated with central adiposity in women may relate to impaired immune response, chronic lowgrade inflammation or a higher prevalence of angiotensin-converting enzyme 2 receptors (SARS-CoV-2 entry point) in the adipose tissue [1] . In men, most associations were non-significant (more limited sample size and power), except some inverse associations warranting further investigations, yet with a potential underlying mechanistic hypothesis involving reduced testosterone levels in obese men while testosterone would facilitate SARS-CoV-2 interaction with the angiotensin-converting enzyme 2 receptor [6] . Study strengths are the exhaustive seroprevalence assessment with highly sensitive assays (able to detect antibodies even in asymptomatic/mild cases) [5, 7] , independent of whether or not the participant sought testing in a large population-based sample with detailed phenotyping (including anthropometric data). Yet, there are some limitations: the imperfect sensitivity of the ELISA-S test [5, 7] and a possible decrease of antibodies over time potentially resulting in some misclassification. Waist and hip circumference data were collected in June 2020 and may be either post-, contemporary to or pre-SARS-CoV-2 infection (whereas most anthropometric data were collected before potential SARS-CoV-2 infection, allowing a prospective design: self-reported but validated [8] body weight measures, and measured body composition data but acquired long before the COVID-19 crisis), potentially resulting in some reverse causality bias if SARS-CoV-2 infection led to weight loss.

This study highlights central adiposity as an important factor to consider when looking at factors associated with a higher susceptibility to SARS-CoV-2 infection (e.g. for risk stratification in the population). This is all the more relevant since the excess weight has been shown to increase the smoker, smoker), children and/or grandchildren aged under 18 years at home during the lockdown (yes/no), residential area during the lockdown (rural area/city < 20,000 inhabitants/city ≥ 20,000 to 100,000 inhabitants/city > 100,000 inhabitants), frequency of going out over the past week during the lockdown (never/once/two to five times/6-10 times/>10 times), prevalent chronic disease (cancer, cardiovascular disease, high blood pressure, diabetes, dyslipidemia: yes/no), regional residential area during the lockdown (Paris Basin/Center-East/East/Mediterranean/North/West/Paris region/ Southwest) and month of blood draw (May-June/July/August-September-October). SD values were as follows: BMI before lockdown, SD risk for developing severe forms of COVID-19, once infected.

Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships

Modifiable and non-modifiable risk factors for COVID-19, and comparison to risk factors for influenza and pneumonia: results from a UK Biobank prospective cohort study

The Nutrinet-Santé study: a web-based prospective study on the relationship between nutrition and health and determinants of dietary patterns and nutritional status

Incidence and risk factors of COVID-19-like symptoms in the French general population during the lockdown period: a multi-cohort study

Antibody status and cumulative incidence of SARS-CoV-2 infection among adults in three regions of France following the first lockdown and associated risk factors: a multicohort study

Testosterone in COVID-19 -foe, friend or fatal victim?

Analytical evaluation and critical appraisal of early commercial SARS-CoV-2 immunoassays for routine use in a diagnostic laboratory

Validity of web-based self-reported weight and height: results of the Nutrinet-Sante study

Email: m.deschasaux@eren.smbh.univ-paris13

Prof. Fabrice Carrat reports personal fees from Imaxio and Sanofi, outside the submitted work. All other authors declare no conflict of interest. 

Additional Supporting Information may be found in the online version of this article:Supporting Information