key: cord-0697666-mubp88nl authors: Klang, Eyal; Kassim, Gassan; Soffer, Shelly; Freeman, Robert; Levin, Matthew A; Reich, David L title: Morbid Obesity as an Independent Risk Factor for COVID‐19 Mortality in Hospitalized Patients Younger than 50 date: 2020-05-23 journal: Obesity (Silver Spring) DOI: 10.1002/oby.22913 sha: 421fb8b99998185c390119bdc8792ed675b884f8 doc_id: 697666 cord_uid: mubp88nl OBJECTIVE: COVID‐19 continues to spread and younger patients are also being critically affected. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. METHODS: We retrospectively analyzed data of COVID‐19 patients hospitalized to a large academic hospital system in New York City between March 1st and May 17th, 2020. Data included demographics, comorbidities, BMI and smoking status. Obesity groups included: BMI 30–40 kg/m(2) and BMI ≥ 40 kg/m(2). Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. RESULTS: Overall, 3,406 patients were included. 572 (17.0%) of the patients were younger than 50. In the younger age group, 60 (10.5%) patients died. In the older age group, 1,076 (38.0%) patients died. For the younger population, BMI above 40 kg/m(2) was independently associated with mortality (aOR 5.1, 95% CI 2.3–11.1). For the older population, BMI above 40 kg/m2 was also independently associated with mortality to a lesser extent (aOR 1.6, 95% CI 1.2 – 2.3). CONCLUSION: Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID‐19. This is particularly relevant in the western world where obesity rates are high. The coronavirus disease 2019 (COVID-19) is a pandemic viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the Centers for Disease Control and Prevention (CDC), as of May 19, 2020, 1.48 million patients have tested positive to COVID-19 in the US. Of those, 89,407 (6.0%) patients have died (1). As the COVID-19 continues to spread the younger population is also being critically affected. Comorbidities such as coronary artery disease (CAD), hypertension (HTN), and diabetes mellitus (DM) have been identified as risk factors for hospitalization and mortality (2, 3) . Obesity was also shown as an important risk factor for severe COVID-19 disease (4, 5) . In previous publications, the median age of COVID-19 patients was around 60 years and thus the risk factors that were highlighted are predominantly in the older population (2, 6, 7) . Identifying comorbidities linked to poor outcome in the young is crucial. This study analyzed obesity as an independent risk factor for mortality in hospitalized patients younger than fifty. We retrospectively analyzed data of COVID-19 patients hospitalized to a large academic hospital system in New York City. Data The analysis was performed with Python (ver. 3.6.5, 64 bits). A p-value of < 0.05 was considered statistically significant. The primary outcome was in-hospital mortality. Calculations were performed separately for patients aged 50 and under, and for patients over 50 years of age. Univariate analysis separately compared comorbidities associated with mortality in the younger and older groups. Categorical variables were compared using Fisher's exact test. Continuous variables were compared using Mann Whitney U-test. Multivariable logistic regression models identified variables independently associated with mortality in patients younger and older than 50. Models were adjusted for demographics and comorbidities ( Table 2) . Adjusted odds ratios (aOR), 95% confidence intervals (CI), and p-values were calculated for the variables in the models. A multivariable analysis for intubation and mechanical ventilation as a secondary outcome was also performed. The covariates in this model were the same as the mortality model. Overall, 4,705 COVID-19 hospitalized patients were identified. We excluded 1,047 patients who were still hospitalized during the study period, and 252 patients with missing BMI. The final cohort included 3,406 patients. 572 patients were younger than 50 and 2,834 patients were older than 50. Characteristics of the survivors and non-survivors are presented in Table 1 . In the younger age group, 60 (10.5%) patients died. In the older age group, 1076 (38.0%) patients died. In univariate analysis, for the younger group, BMI ≥ 40 kg/m 2 was significantly associated with mortality (p < 0.001). For the older population, CAD (p < 0.001), congestive heart failure (CHF) This article is protected by copyright. All rights reserved (p < 0.001), HTN (p < 0.001), DM (p < 0.001), hyperlipidemia (p < 0.001), and chronic kidney disease (CKD) (p < 0.001), were associated with increased mortality. Figure 1 presents a boxplot for BMI values in the younger and older groups, stratified by mortality status. In the never-smoking group, BMI ≥ 40 kg/m 2 was significantly associated with mortality in the younger age group (19.2% mortality with morbid obesity vs. 7.8% mortality without morbid obesity, p = 0.019), but not in the older age group (39.6% mortality with morbid obesity obese vs. 37.1% mortality without morbid obesity, p = 0.254). The median BMI for African Americans was 28.8 (IQR 24.0-35.6) and for Caucasians 27.3 (IQR 23.0-31.6). In multivariable analysis, for the younger population, BMI above 40 kg/m 2 was independently associated with mortality (aOR 5.1, 95% CI 2.3 -11.1) ( Table 2) For the secondary outcome, intubation and mechanical ventilation status was independently associated with BMI ≥ 40 kg/m 2 , both in the young age group (aOR 4.1, 95% CI 2.1 -8.2) and in the older age group (aOR 1.5, 95% CI 1.1 -2.1) (supplementary Table 1 ). Our study highlights that the comorbidity profile associated with COVID-19 mortality is different for younger patients. Morbid obesity (BMI ≥ 40 kg/m 2 ) was found to strongly and independently associated with mortality in hospitalized patients younger than 50. Morbid obesity was also associated with intubation and mechanical ventilation. Like previous research, other than obesity, CAD, DM, and CKD were independently associated with mortality in the older population. Several recent studies highlighted obesity as a risk factor for COVID-19. These studies showed that obesity was more frequent among COVID-19 patients and was associated with increased need for invasive mechanical ventilation (8, 9) . Another study identified obesity as a risk factor for This article is protected by copyright. All rights reserved hospitalization in patients younger than 60 (4). Our results identified that younger patients with BMI above 40 kg/m 2 are 5 times more likely to die. This is of concern as the prevalence of obesity among US young adults is approximately 40% (10) . Thus, although the younger population is considered at a lower risk for COVID-19 mortality, young morbidly obese patients are an important high-risk population. The link between obesity and COVID-19 severity has not been established yet. Several mechanisms that may explain the obesity role in the pathogenesis of the disease have been suggested. Patients with obesity are associated with impaired immune response and abnormal secretion of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-a) (11) . Furthermore, obesity results in physiological lung alteration such as decreased functional residual capacity and hypoxemia (12) . Lastly, angiotensin-converting enzyme 2 (ACE2) is expressed in adipose tissue and ACE2 was also shown to have high affinity to the COVID-19 virus (13) . Interestingly, in our study, the effects of obesity on the COVID-19 disease are independent of obesity-related comorbidities such as diabetes and CVD. Ryan et al. suggested that the burden of increased adipose tissue in the morbidly obese plays a key role in the pathogenicity of COVID-19 (14) . They proposed that adipose tissue is a pro-immunogenic and richly vascularized organ with the ability to augment the pro-inflammatory response to viral infection. The adipose tissue has the potential to prolong viral shedding in an environment that is already inflamed with local cytokine amplification (14) . This study was limited by its retrospective nature and by the small number of patients younger than 50. This resulted in relatively wide confidence intervals for the younger population. Nonetheless, morbid obesity was found to be strongly and independently associated with mortality in this population. Moreover, the association between obesity and mortality is intricate and may involve other covariates that may have not been accounted for in our study. Additionally, in our study African Americans had a slightly lower adjusted risk for death. Ethnicity data was incomplete in our study, and thus was not included in the calculations. The intricate correlations between race, ethnicity, marital status and socioeconomic status and COVID-19 disease should be further studied. Finally, as this is an ongoing pandemic, patients who remained hospitalized were not included in the study and this may have biased the results as well as the mortality rates. Our study demonstrates that hospitalized patients younger than 50 with morbid obesity are more likely to die from COVID-19. This is particularly relevant in the western world where obesity rates are high. This article is protected by copyright. All rights reserved COVID-19): cases in US Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission Association of Obesity with Disease Severity among Patients with COVID-19 Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation Accepted Article This article is protected by copyright. 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