key: cord-351223-nnuoadh6
authors: Pettit, Natasha N.; MacKenzie, Erica L.; Ridgway, Jessica; Pursell, Kenneth; Ash, Daniel; Patel, Bhakti; Pho, Mai T.
title: Obesity is Associated with Increased Risk for Mortality Among Hospitalized Patients with COVID‐19
date: 2020-06-26
journal: Obesity (Silver Spring)
DOI: 10.1002/oby.22941
sha: 
doc_id: 351223
cord_uid: nnuoadh6

OBJECTIVE: Obesity has been identified as a risk factor for severe COVID‐19 caused by the SARS‐CoV2 virus, however a direct association with mortality has not been reported. We sought to determine whether obesity is a risk factor for mortality among COVID‐19 patients. METHODS: The study was a retrospective cohort, including patients with COVID‐19 between March 1 and April 18, 2020. The primary objective was to determine if obesity is a predictor of mortality. RESULTS: A total of 238 patients were included, 218 patients (91.6%) were African American, 113 (47.5%) were male, and the mean age was 58.5 years. Of the included patients, 146 (61.3%) were obese (BMI >30kg/m(2)), with 63 (26.5%), 29 (12.2%), and 54 (22.7%) with class 1, 2, and 3 obesity, respectively. Obesity was identified as a predictor for mortality (OR 1.7(1.1‐2.8),p=0.016), as was male gender (OR 5.2(1.6‐16.5),p=0.01) and older age (OR 3.6(2.0‐6.3),p<0.0005). Obesity (OR 1.7(1.3‐2.1),p<0.0005) and older age (OR 1.3(1.0‐1.6),p=0.03) were also risk factors for hypoxemia. CONCLUSIONS: Obesity was found to be a significant predictor for mortality among inpatients with COVID‐19 after adjusting for age, gender, and other comorbidities. Patients with obesity were also more likely to present with hypoxemia.

Conclusions: Obesity was found to be a significant predictor for mortality among inpatients with COVID-19 after adjusting for age, gender, and other comorbidities. Patients with obesity were also more likely to present with hypoxemia.

Several risk factors for severe disease and poor outcomes in coronavirus disease 2019 (COVID-19) have been identified. [1] [2] [3] [4] [5] [6] [7] Early reports from Chinese series identified hypertension, diabetes, chronic pulmonary disease, and cardiovascular disease as the comorbidities most consistently associated with hospitalization, respiratory support, intensive care unit (ICU) admission, and death in COVID-19 patients. Subsequent reports from the United States and Europe suggested that patients with a higher body mass index (BMI) are at greater risk for hospital admission and severe disease requiring respiratory support. 8, 9 Based on these reports that many patients hospitalized for COVID-19 had a BMI >30kg/m 2 , we sought to evaluate whether obesity was associated with all-cause mortality in hospitalized patients with confirmed COVID-19 at a single academic medical center. We also examined the association between obesity and secondary outcomes including hypoxemia upon hospital admission, ICU admission at any point, mechanical ventilation at any point, and hospital length of stay.

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All SARS-CoV2 positive patients admitted to the University of Chicago Medical Center, an 811bed academic medical center on the south side of Chicago, between March 1, 2020 and April 18, 2020 who had completed their hospital course (including deceased patients) were included in the analysis. A diagnosis of COVID-19 required a positive SARS-CoV2 test using the Roche Cobas® SARS-CoV-2 RT-PCR high-throughput assay or Xpert Xpress® SARS-CoV-2 assay. 10 11 Information was recorded on patient age, race/ethnicity, BMI, comorbidities, COVID-19directed therapies (antivirals, IL-6 cytokine inhibitor therapy), admission oxygen requirement, and survival-to-discharge. Admission to the ICU, need for mechanical ventilation, and hospital length of stay were also documented. The primary analysis was the relationship between the primary endpoint of all-cause mortality and BMI group after multivariable adjustment for demographics and comorbidities. Secondary analyses included assessing the association of BMI group with oxygen requirement upon hospital admission, length of stay, ICU admission at any point, and mechanical ventilation at any point.

Data are reported as median (interquartile range) or mean (standard deviation) for continuous variables and as frequency (percentage) for categorical variables. Tests of significance for differences between obesity groups were done using the Kruskal-Wallis test for continuous variables, and the Fisher's exact test for categorical variables. Effects of obesity on mortality and admission hypoxemia were assessed using a multivariable logistic regression with an additive effects model to adjust for comorbid. A p-value < 0.05 was considered significant for This article is protected by copyright. All rights reserved.

covariates in the multivariable analysis, and bivariate analyses were also done for all covariates in the multivariable model. Bonferroni correction was applied to all univariate and bivariate pvalues to control the family-wise error rate at 0.05. All statistical analyses were performed with STATA version 15.0. This project received a formal Determination of Quality Improvement status according to University of Chicago Medicine institutional policy. As such, this initiative was deemed not human subjects research and was therefore not reviewed by the Institutional Review Board.

A total of 238 patients with COVID-19 were included. Baseline characteristics, length of stay, and mortality rates for each of the 5 BMI categories are shown in after Bonferroni correction). The majority of patients were African American (91.6%). The most common comorbidities were hypertension (52.9%), diabetes (28.6%), pulmonary disease (26.5%), and cardiovascular disease (21.4%). More patients in the higher obesity groups had diabetes.

On hospital admission, 98 (41.2%) of patients were on room air, 120 (50.4%) required 1-5L supplemental oxygen via nasal cannula, and 12 (5%) required oxygen supplementation of 6L via nasal cannula or more. Four patients (1.7%) required high-flow nasal cannula and an additional This article is protected by copyright. All rights reserved.

4 patients (1.7%) were intubated on presentation. Patients with obesity were more likely to require supplemental oxygen on presentation compared to normal weight patients (32.6% of normal weight patients requiring supplemental oxygen vs 58.7% in class 1 obesity, 62.1% in class 2 obesity, and 77.8% in class 3 obesity, Fisher's exact test p < 0.001).

Approximately 70% of patients received COVID-19 directed therapy (antivirals and/or immunemodulators). About one-quarter of patients (27.3%) eventually required ICU admission and 14.7% were intubated during their hospital course. The overall median length of stay was 5 (IQR 3-8) days and the overall mortality rate was 10.1%. There were no significant differences between groups with respect to these outcomes. Table 3 summarizes the results of the regression analyses for mortality and hypoxemia on admission. Obesity, male gender, and older age were associated with increased mortality.

Significant predictors for hypoxemia on admission included obesity and age as well. Older age was the only variable associated with ICU admission after multivariable adjustment for other covariates (OR 1.4, 95% CI 1.1-1.8, p=0.01, data not shown). Older age (OR 1.6, 95% CI 1.2-2.2, p=0.01) was associated with requirement for mechanical ventilation (data not shown). None of the variables assessed were significantly associated with length of stay after multivariable adjustment (data not shown).

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Our study shows that amongst hospitalized patients with COVID-19 infection, obesity was significantly associated with mortality after adjusting for age, gender, and other comorbidities.

For every increase from one BMI category to the next, there was a 70% increased odds of mortality in the multivariable model. This finding provides further evidence that obesity is a key comorbidity in COVID-19 that may not only predict severe disease requiring hospital admission, oxygen supplementation, or mechanical ventilation, but may also predict increased mortality. 8, 9 We also found that older age and male gender was significantly associated with mortality, as has elsewhere been reported. [1] [2] [3] [4] [5] [6] [7] Although patients with obesity in our study were more likely to require supplemental oxygen on admission, there was no significant association between obesity and the need for ICU admission or mechanical ventilation throughout the hospital stay.

This may reflect our small sample size or our institution's practice of using high-flow nasal cannula or helmet ventilation rather than intubation for respiratory support, when possible.

Our finding of an association between obesity and severe COVID-19 with poor clinical outcomes is congruent with what has been observed with other severe viral infections, including H1N1.

Obesity was found to be associated with an increased risk of severe disease, hospitalization, and death during the 2009 H1N1 influenza pandemic. 12, 13 There is evidence that impaired lung mechanics and higher concentrations of pro-inflammatory molecules may both contribute to the propensity in patients with obesity to develop more severe complications from respiratory viral infections. Abdominal obesity restricts the movement of the diaphragm and chest wall, This article is protected by copyright. All rights reserved.

resulting in a reduction in functional residual capacity and making mechanical ventilation more challenging. 14, 15 Patients with obesity are also known to have higher concentrations of proinflammatory cytokines and adipokines (e.g. leptin, alpha-TNF, MCP-1, and IL-6) and lower antiinflammatory adipokine concentrations (e.g. adiponectin) which can result in a dysregulated immune response. 16 Our study has several limitations, including small sample size and use of retrospective observational analysis. Additionally, >90% of the patients in our study population were African American, potentially limiting applicability of our results to other populations and limiting our ability to examine the relationship between race, obesity, and severe illness. As we did not evaluate cause of death, we were unable to assess whether there is a common pathway to mortality in COVID-19 patients with obesity.

Our findings add further weight to the evidence that patients with obesity are at greater risk for severe disease and mortality in COVID-19. Future studies reporting on the COVID-19 patient population should include obesity as a comorbidity to validate and account for these findings.

Additional studies are also needed to further explore the relationship between race and obesity in severe disease. (7) 2 (4.1) 0 (0) 0 (0) 5 (9.3) 0.08 * significant after Bonferroni correction for multiple comparisons (p < 0.0038) †Asthma, chronic obstructive pulmonary disease, bronchitis, sarcoidosis, obstructive sleep apnea ‡ Coronary artery disease, heart failure, valvular heart disease, arrhythmia Abbreviations: BMI: body mass index; SD: standard deviation; VTE: venous thromboembolism This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. 

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