Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York

1. Introduction

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved to a global pandemic with more than two million confirmed cases and about 200 thousand deaths so far [1]. The first cases in the United States (U.S.) were reported on January 19th, 2020 in the Washington state [2]. Since then, about one million confirmed cases and sixty thousand deaths have been reported [3]. New York City (NYC) is the current epicenter of the pandemic with about 160 thousand confirmed cases and more than twelve thousand deaths to date [4]. Early reports from Asia and Europe have identified older age, male sex, and chronic medical conditions, such as diabetes, hypertension, obesity, coronary artery disease, and heart failure, as risk factors associated with worse outcomes [[5], [6], [7]]. However, little is known about the risk factors and the characteristics of the disease in the United States population and particularly in underrepresented minorities, who appear to be affected disproportionally by COVID-19 [4,7]. The age-adjusted death rate per 100,000 people in NYC is more than double for African Americans compared to Whites (127.1 vs. 63.5) [4]. The higher prevalence of medical conditions that are considered risk factors for severe COVID-19 among African Americans and the higher risk for exposure to SARS-CoV-2 due to living and working conditions seem to be plausible explanations for the observed disproportionate differences in outcomes [7]. The Bronx, which is the most diverse area in the United States as per the 2010 U.S. Census, ranks last among all 62 counties of New York state in health outcomes, quality of life and important health and socioeconomic factors according to County Health Rankings and Roadmaps [8]. In addition, the Bronx has the highest obesity rates among all NYC boroughs and stands remarkably higher than the national average [9,10].

Our primary objective with this analysis was to investigate whether obesity is associated with worse in-hospital outcomes. Our secondary objective was to assess and present the clinical characteristics and early outcomes of the first 200 patients, who were diagnosed with COVID-19 and admitted to a large tertiary academic center.

2. Materials and methods

3. Results

In total, 200 patients admitted with COVID-19 were included in this analysis (female sex = 102, BMI < 25 kg/m² = 38, BMI 25–34 kg/m² = 116, and BMI ≥ 35 kg/m² = 46). The median BMI was 30 (IQR 26–35) kg/m². Most of our patients were either of African American race (51%) or of Hispanic ethnicity (34.5%). 23.5% were SNF residents. The median age of the whole cohort was 64 (50–73.5) years, with significant differences among the three groups [BMI < 25 kg/m²: 73 (64–80) vs. BMI 25–34 kg/m²: 63 (48.5–71) vs. BMI ≥ 35 kg/m²: 57.5 (45–67), p < 0.001]. 32.5% of our cohort was active or past smokers. Hypertension, hyperlipidemia and coronary artery disease were prevalent in 76%, 46.2% and 16.5% of our patients, respectively. 17% had a history of heart failure while 27.5% had a history of asthma or COPD. 29% had a history of chronic kidney disease or ESRD. Diabetes was prevalent in 39.5% of our patients. The detailed baseline demographic and clinical characteristics are presented in Table 1 .

Fever (86%), cough (76.5%), dyspnea (68%) and malaise (58%) were the four most common symptoms. The median SO₂ on the first hospital day was 95% (IQR 89–97) without significant differences among groups. Symptoms and signs are presented in Table 2 . All 200 patients received chest X-ray on presentation, with 55.5% of them having bilateral infiltrates and 27% having only unilateral findings. The laboratory and radiologic findings are presented in Table 3 .

In total, 24% of our cohort died during hospitalization, with higher rates among individuals with severe obesity (BMI < 25 kg/m²: 31.6%, BMI 25–34 kg/m²: 17.2%, BMI ≥ 35 kg/m²: 34.8%, p = 0.030). Similarly, patients with severe obesity were more likely to undergo intubation (BMI < 25 kg/m²: 18.4%, BMI 25–34 kg/m²: 16.4%, BMI ≥ 35 kg/m²: 34.8%, p = 0.032). In total, 45% of our patients had increasing oxygen requirements during hospital stay without significant differences among BMI groups. Twenty-two percent developed ARDS and 16% spent at least one night in the ICU. In-hospital outcomes are presented in Table 4 and in Fig. 1 .

4. Discussion

Our study described the baseline characteristics, clinical features, and early outcomes of the first 200 patients who were hospitalized due to COVID-19 in an institution which mainly serves African American and Hispanic population. This is the first study that has performed joint evaluation of age, gender, obesity and multiple comorbidities that have previously been linked with adverse outcomes. The main findings can be summarized as following: 1) the in-hospital mortality was 24% with only 3% patients still hospitalized on the 21-day follow-up 2) severe obesity (BMI ≥ 35 kg/m²), increasing age, and male sex are independently associated with mortality and need for intubation 3) severe obesity (BMI ≥ 35 kg/m²), increasing age, male sex, and smoking were also independently associated with increasing oxygen requirements during hospitalization.

Older age and male sex have already been described as risks factor for severe disease and death in patients with COVID-19 [5,[11], [12], [13], [14], [15], [16]], although large outcome studies are needed to assess the latter. The most interesting finding of our analysis is that severe obesity is a significant factor for severe respiratory disease and death in hospitalized patients with COVID-19. It should be pointed out that this association remained significant even after adjusting for several clinical entities, such as diabetes, coronary artery disease, heart failure, COPD, CKD or ESRD, and smoking, which indicates that obesity may predispose to negative outcomes independently. The higher mortality rates in the BMI < 25 kg/m² and BMI ≥ 35 kg/m² groups allow to make a hypothesis of a J-shaped distribution between BMI and mortality. However, this was not confirmed in our adjusted analysis presumably because of our small sample and the inherent co-existing factors associated with BMI < 25 (older age, frailty).

Other preliminary published data have linked obesity to severe COVID-19. A large cohort from New York City depicted that obesity is strongly associated with progression to critical illness with substantially higher odds ratio than any cardiovascular or pulmonary disease (BMI 30–40 kg/m² OR: 1.38; 95% CI: 1.03–1.85; BMI > 40 kg/m² OR: 1.73; 95% CI: 1.03–2.90) [17]. A cohort from China revealed that obesity significantly increases the risk for developing severe pneumonia in the setting of COVID-19 (OR: 3.42; 95% CI: 1.42–8.27) [18]. Another report from China indicated that the presence of obesity in patients with metabolic-associated fatty liver disease is associated with an almost 6-fold increased risk of severe COVID-19 [19]. Obesity could partially explain why the mortality rate for COVID-19 is higher in countries with higher prevalence of obesity, such as Italy, as compared to China and Japan [20]. Variables such as diabetes and other cardiovascular and pulmonary comorbidities were found to have a significant association in prior reports from China and Italy [[11], [12], [13], [14]]. However, most of these were obtained from univariate estimates only. In our multivariate analyses it was shown that these comorbidities are likely epiphenomena since they are not independent from male gender, older age or obesity which may be the underlying link.

Our findings on the association of severe obesity to mortality in COVID-19 are not unanticipated given our prior experience from the 2009 pandemic influenza (H1N1) disease. Morgan et al. reported significant association of obesity to death in adult patients without recognized pre-existing medical conditions hospitalized with H1N1 influenza disease (obesity OR: 3.1; 95% CI: 1.5–6.6; morbid obesity OR: 7.6; 95% CI: 2.1–27.9) [21]. Obesity leads to increased work of breathing by augmenting the airway resistance and is associated with decreased expiratory reserve volume, functional capacity, and pulmonary compliance [22,23]. Central obesity results in decreased diaphragmatic excursion in supine patients compromising ventilation [23]. Moreover, obesity is a chronic inflammatory state with increased circulating levels of pro-inflammatory cytokines, including interleukin-6, and is known to impair the immune system [24,25]. The observed association between severe obesity and mortality may also underlie the observed association between low vitamin D levels, which are low in the obese, and mortality and needs to be explored further [25].

The in-hospital mortality rate on 21-day follow-up in our cohort is 24%. Three inpatient cohorts from China reported in-hospital mortality rates of 28.2%, 11.7%, and 17%, respectively [5,11,12]. A large cross-sectional study from New York City, which did not include hospitals located in the Bronx, reported a 14.6% mortality rate in the inpatient sample to the time of the analysis, however 35.9% of the patients were still hospitalized, which indicates that the final inpatient mortality rate may be actually higher [16]. Large retrospective cohorts that will probably be published in the following months will accurately estimate the in-hospital mortality in the Bronx and elsewhere.

In total, 33.6% of adults in the Bronx are obese, a number which is much higher than all other NYC boroughs, while the prevalence of obesity nationally is 20% [9,10]. The Bronx has the highest rate of diabetes among all sixty-two counties of the New York state and one of the highest rates of hypertension [26]. Additionally, the prevalence of obesity is higher among individuals of lower socioeconomic status (>35%) and substantially higher in non-Hispanic blacks (36%) and Hispanic (35.4%) as compared to non-Hispanic whites (19.1%) [9]. The patient population that our institution serves mainly includes patients of lower socioeconomic status and people that identify themselves as African American or Hispanic. The combination of these two made up 85.5% of our current study population that is representative of racial and ethnical distribution in the Bronx [27]. The median income, as estimated by the zip codes based on publicly available data provided by the internal revenue service, was not found to be a risk factor for worse outcomes in our study, which is explained by the fact that the Bronx is a homogenous area of low income.

We report that active or prior smoking was associated with increasing oxygen requirements during hospitalization. This is in contrast to the results of a recent meta-analysis of five studies from China which concluded that active smoking did not seem to be significantly associated with higher risk of progressing to severe COVID-19 [28]. Large observational studies and future meta-analyses will elucidate the association of smoking with COVID-19 severity and other outcomes.

One of the strengths of the current study is that our included patients represent underserved and economically disadvantaged minorities; thus, revealing the early outcomes of COVID-19 in this vulnerable population and usually underreported and underrepresented in clinical research. Additionally, two researchers independently and blindly collected data which reduces errors and bias. On the other hand, our study has several limitations. First, our sample was relatively small, but given the nature of the evolving pandemic, it was of paramount importance to make our early data and findings widely available as soon as possible, especially given the lack of data up to date in COVID-19 in minorities and underserved population. We noted that among elderly, not only high BMI but also BMI <25 was associated with worse in-hospital outcomes. Therefore, we proceeded to interaction analyses between variables that were shown to be associated with the outcomes in the adjusted analyses (BMI, age, sex) but no correlation was found. Given that our study size was relatively small, future larger studies need to explore effect modification and the interaction between these variables. Second, this was a real-world study with a retrospective design utilizing the electronic medical records, which is suboptimal compared to a prospective study that could have more accurate follow-up assessment. Third, the rapidly changing management of COVID-19 might have affected our results but it is highly unlikely that this could have differentially affected associations between obesity and mortality. Fourth, we handled BMI as a categorical variable in the regression analysis with cut-off points largely representing quartiles of BMI. However, we also performed additional analyses with BMI as a dichotomous (cut-off: 35 kg/m²) or a continuous variable and the significant associations persisted.

In conclusion in this cohort of hospitalized patients with COVID-19 in an underserved, minority- predominant population in the Bronx, we found that severe obesity was associated with higher in-hospital mortality even after adjusting for other pertinent potentially confounding factors. Particular attention should be paid in preventing obesity and its complications and protecting this population from COVID-19 given the higher chance for adverse outcomes once they are diagnosed with the disease. In addition, obese patients diagnosed with COVID-19 should be treated with particular attention given the possible higher risk for adverse outcomes. While we recognize the limitations, we hope that our study will stimulate additional researchers to further study the effect of obesity in COVID-19 and outcomes of minorities diagnosed with COVID-19. Larger cohort studies are needed to confirm our data and pilot clinical trials are needed to assess whether pharmacotherapy for obesity and its comorbidities may improve outcomes in the short or the long term.

Funding

No funding was available for this study.

CRediT authorship contribution statement

Leonidas Palaiodimos: Conceptualization, Methodology, Data curation, Investigation, Validation, Writing - original draft. Damianos G. Kokkinidis: Conceptualization, Methodology, Formal analysis, Investigation, Writing - original draft. Weijia Li: Data curation, Investigation, Visualization, Resources. Dimitrios Karamanis: Methodology, Software, Formal analysis, Investigation, Visualization. Jennifer Ognibene: Software, Resources, Data curation, Visualization. Shitij Arora: Validation, Investigation, Writing - review & editing. William N. Southern: Validation, Investigation, Writing - review & editing. Christos S. Mantzoros: Investigation, Formal analysis, Validation, Writing - review & editing, Supervision, Methodology.

Declaration of competing interest

All authors declare no conflict of interests.