key: cord-0714104-9jswjjsn
authors: Bui, Dinh S.; Cassim, Raisa; Russell, Melissa A.; Doherty, Alice; Lowe, Adrian J.; Agusti, Alvar; Dharmage, Shyamali C.; Lodge, Caroline J.
title: Lung Function Levels Influence the Association between Obesity and Risk of COVID-19
date: 2021-03-30
journal: American journal of respiratory and critical care medicine
DOI: 10.1164/rccm.202105-1100le
sha: ed6861b07ba9d17bd3c10c729f07e52c26a73cc0
doc_id: 714104
cord_uid: 9jswjjsn

nan

data on SARS-CoV-2 test results (for the period of March 16 to November 24, 2020) derives from the English subgroup alone. Body mass index (BMI) at recruitment (baseline) was used to define normal (BMI , 25), overweight (25 < BMI , 30), and obese (BMI > 30) groups. FEV 1 , FVC, and their ratio at baseline were categorized using the median and quartiles (of their z-score values). Multivariable logistic regression models were generated to investigate the association of obesity with SARS-CoV-2 positivity adjusting for age, sex, smoking, socioeconomic status (Townsend index), diabetes, cardiovascular disease, physical activity, and ethnicity. Stratified analyses for lung function levels and formal interaction tests to investigate potential effect modification were conducted.

Of the 36,896 participants tested (mean age 69.3 6 8.3 years), 5,757 were positive for SARS-CoV-2. Characteristics of those who tested positive and those who tested negative are shown in Table 1 . The prevalence of overweight and obesity were 42.3% and 29.0%, respectively. Compared with normal weight, both overweight (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.12-1.30) and obesity (OR, 1.31; 95% CI, 1.21-1.42) were associated with increased risk of testing positive for SARS-CoV-2, with the risk being greater in those who were obese than in those who were overweight (P = 0.017). The association between obesity and SARS-CoV-2 positivity was stronger in those with FEV 1 below the median (OR, 1.48; 95% CI, 1.29-1.71) than in those with FEV 1 above the median (OR, 1.22; 95% CI, 1.07-1.38; P for interaction = 0.02). The interaction was also stronger for FVC below the median (OR, 1.47; 95% CI, 1.28-1.69) compared with FVC above the median (OR, 1.28; 95% CI, 1.12-1.46; P for interaction = 0.002). Similar patterns were observed when stratifying the association between obesity and SARS-CoV-2 positivity by quartiles of lung function (both FEV 1 and FVC) ( Table 2) . We also observed significant interactions when FEV 1 and FVC were modeled as continuous variables (Pinteraction = 0.01 and 0.008, respectively). For overweight, the association appeared to be weaker among the poor lung function group, but this difference was not significant (P-interaction = 0.7 and 0.14 for FEV 1 . When underweight (BMI , 18.5) was investigated as a separate group, it was associated with reduced risk of testing positive for SARS-CoV-2 (OR, 0.53; 95% CI, 0.30-0.95). We were unable to stratify the analysis for lung function owing to the small sample size.

An early analysis of a smaller sample (n = 2,494) of the UK Biobank study suggested associations between overweight and obesity and SARS-CoV-2 test positivity (2) . Other analyses (n = 4,855 and 5,623) of the same cohort assessed the interaction between obesity and ethnicity (3, 4) . We now confirm the association between obesity and SARS-CoV-2 test positivity in a much larger sample (n = 36,896).

In addition to this, we found that the association between obesity and SARS-CoV-2 was modified by lung function. Although both obesity and low lung function have been shown to increase risk of testing positive for SARS-CoV-2 independently, we observed that these two factors interact to multiplicatively increase risk of SARS-CoV-2 test positivity. Therefore, risk for SARS-CoV-2 test positivity was higher among individuals who were obese who also have low lung function compared with individuals who were obese with normal lung function.

Interestingly, we found that underweight was associated with reduced risk of testing positive for SARS-CoV-2. This association has not been previously reported. However, among those infected with SARS-CoV-2, underweight may be associated with more severe outcomes (6) . This discrepancy regarding risk of testing positive and disease severity in relation to underweight needs to be further investigated. The underlying mechanism for the protective effect of being underweight in our study is not known, but an explanation could be underweight individuals are more likely to have chronic health conditions, diet heavily, and take extra precautions to reduce the risk of contracting the virus.

Our study has some limitations. As this analysis was based on the tested subsample of UK Biobank, it may be prone to some degree of bias (7) . In fact, those included in this analysis had a slightly higher prevalence of obesity compared with the whole cohort (29.0% vs. 24.4%), but we postulate that this issue is unlikely to explain the association found in this study, as we are investigating among obese groups whether lung function modifies risk of SARS-CoV-2 test positivity. Moreover, those included in this analysis and the whole cohort had similar demographic characteristics (Table 3) .

In conclusion, our study found that obesity interacts with low lung function to increase risk of testing positive for SARS-CoV-2 Definition of abbreviations: BMI = body mass index; CI = confidence interval; OR = odds ratio; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. Data are shown as OR (95% CI). *P , 0.01. † P , 0.001. ‡ P value = 0.02 for an overall interaction obtained from the likelihood ratio test with specific P values for interaction terms for overweight and obese of 0.7 and 0.03, respectively. § P , 0.05. jj P value = 0.002 for an overall interaction obtained from the likelihood ratio test with specific P values for interaction terms for overweight and obese of 0.14 and 0.06, respectively.

infection. Our findings suggest that individuals with poor lung function, particularly individuals who are obese, should be encouraged to take extra precautions to reduce the risk of acquiring this disease. In the short term, this may include adhering strictly to mask and social distancing mandates and practicing good hand hygiene to mitigate risk as the pandemic continues.

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Copyright © 2021 by the American Thoracic Society For definition of abbreviations, see Table 1 .