Effect of Obesity on Clinical Outcomes in COVID-19 Patients

Background Obesity is a well-known risk factor for developing severe coronavirus disease 2019 (COVID-19). In this study, we sought to determine the relationship between obesity and poor outcomes in patients with COVID-19 patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. Methods We conducted a single-centered descriptive study of adult COVID-19 patients hospitalized between March 1 and December 31, 2020, at KAUH. Patients were classified according to body mass index (BMI) as overweight (BMI 25-29.9 kg/m2) or obese (BMI ≥30 kg/m2). The main outcomes were admission to the intensive care unit (ICU), intubation, and death. Results Data were analyzed from 300 COVID-19 patients. Most study participants were overweight (61.8%), and 38.2% were obese. The most significant comorbidities were diabetes (46.8%) and hypertension (41.9%). Both hospital mortality (10.4% for obese; 3.8% for overweight, p = 0.021) and intubation rates (34.6% for obese; 22.7% for overweight, p = 0.004) were significantly higher among obese patients than overweight patients. There was no significant difference in terms of ICU admission rate between both groups. However, intubation rates (34.6% for obese; 22.7% for overweight, p = 0.004) and hospital mortality (10.4% for obese; 3.8% for overweight, p = 0.021) were significantly higher among obese patients than overweight patients. Conclusions This study aimed to describe the effect of high BMI on the clinical outcome of COVID-19 patients in Saudi Arabia. Obesity is significantly correlated with poor clinical outcomes in COVID-19. It is also associated with higher mortality and the need for mechanical ventilation necessitating intensive care unit admission. Patients with higher BMI should be prioritized in the hospital setting, as they have a higher potential of developing severe COVID-19 complications and sequelae.


Introduction
The global coronavirus disease 2019 (COVID- 19) pandemic was initially discovered in Wuhan, China, in December 2019 and resulted in a substantial pandemic associated with mortality and morbidities [1]. Comorbidities such as cancer, chronic obstructive pulmonary disease, chronic renal disease, history of solid organ transplant, cardiac problems, type 2 diabetes, and obesity can lead to poor clinical outcomes in the event of developing COVID-19 [2,3].
Obesity was associated with a significantly higher risk of severe pneumonia in hospitalized patients with COVID-19 [4]. According to meta-analysis data, the proportion of obese patients admitted to hospitals with COVID-19, and subsequent mortality increased substantially compared to non-obese patients [5]. Recent studies from numerous countries reported the severity of COVID-19 illness in obese people of varied racial and cultural backgrounds [6][7][8][9]. Studies have also shown that obese patients with COVID-19 are at risk of intensive care unit (ICU) admission and mechanical ventilation for respiratory support [10,11]. Obesity in Saudi Arabia has an estimated prevalence of 28.7% of the population [12]. We conducted this retrospective study to review the relationship between obesity and adverse outcomes in our institute and compare our results to previous studies. This study aimed to describe the effect of high body mass index (BMI) on the clinical outcome of patients with COVID-19 infection among Saudi patients.

Materials And Methods
We conducted a single-centered, retrospective descriptive study at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. After calculating the sample size using the Raosoft sample size calculator (Raosoft, Inc, Seattle, WA). We included 300 obese and overweight COVID-19 patients, aged 18 or older who were admitted to KAUH between March 1 and December 31, 2020. The study excluded any patients younger than 18, pregnant, had a BMI < 25 kg/m 2 , received only outpatient care, or tested negative for COVID-19. Patient samples to confirm COVID-19 were collected from the upper respiratory tract using a nasopharyngeal swab or the lower respiratory tract by endotracheal aspirate. After acquiring the sample, the reverse transcription-polymerase chain reaction confirmed the diagnosis. We collected data using patient medical records with no contact or interaction with participants. The study was a noninterventional observational study involving a review of medical records, so the requirement for written informed consent was waived. The study was approved by the biomedical research unit of KAUH, Jeddah, Saudi Arabia (Reference No. 516-21).

Data collection method
We recorded patient demographic and anthropometric data and comorbidities. Patients were classified according to BMI as overweight (BMI 25-29.9 kg/m 2 ) or obese (BMI > 30 kg/m 2 ) according to World Health Organization guidelines [13]. The main outcomes were admission to the ICU, intubation, and death. Additional variables included length of hospital stay, re-admission, hospital-acquired infection (defined as having a positive culture during one admission period), re-intubation, noninvasive ventilation, and treatments (such as therapeutic anticoagulation, tocilizumab, corticosteroids, and plasma exchange).

Statistical analysis
The statistical analysis was performed using RStudio (R version 4.1.1). Descriptive statistics were used for categorical data (frequencies and percentages) and numerical data (means and standard deviation). The differences between BMI groups (overweight and obesity) were tested using a Chi-squared test or Fisher's exact test for categorical variables. Factors associated with the primary outcomes were assessed by a univariate logistic regression analysis using the primary outcome variable as a dependent variable (intubation, ICU admission, or death) and the demographic variables and comorbidities as independent variables (each in a separate univariate model). In the instance of indicating multiple associations with the independent variables, we constructed a multivariate binary logistic regression model to assess the independent predictors of the outcome variables. Data were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Statistical significance was considered at p < 0.05.

Demographic characteristics and clinical history of patients
Data were retrieved from 300 patients with a confirmed COVID-19 infection. Approximately two-thirds of them were males (63.3%) and patients aged ≥ 45 years represented 73.4% of the sample. Based on the BMI categories, less than half of the patients were obese (38.3%), whereas overweight patients represented 61.7% of the participants. The proportion of females in the obese group (49.6%) was significantly higher than those in the overweight group (28.6%, p < 0.001). Additionally, the proportion of obese patients among older adults was significantly higher than their overweight counterparts (44.3% vs 31.9%, p = 0.036) ( Table 1).  The most commonly reported comorbidities were diabetes mellitus (47.0%) and cardiovascular diseases (43.7%, Figure 1).

FIGURE 1: A bar chart depicting the percentages of comorbidities among patients under study.
Obesity was significantly associated with having a history of cardiovascular disease (54.8% among obese patients vs 36.8% among overweight, p = 0.002) and a history of chronic kidney disease (7.0% among obese patients vs 1.1% among overweight, p = 0.008, Table 2).

The association between hospital complications and both BMI categories
Regarding the characteristics of hospitalization, there were no significant differences between overweight and obese patients in terms of the rate of ICU admission. However, the proportion of obese patients who required intubation (11.6%) was significantly higher than those in the overweight group (2.7%, p = 0.002). Additionally, the proportion of dead patients in the obese group was significantly higher than their 2023  counterparts in the overweight groups (10.4% and 3.8%, respectively, p = 0.021, Table 3).

Factors associated with the primary outcomes
Results of the univariate regression analysis showed that intubation was significantly associated with being obese (OR = 4.7, 95% CI, 1.7 to 15.0, p = 0.004). Additionally, ICU admission was significantly higher among males compared to females (OR = 2.8, 95% CI, 1.4 to 6.2, p = 0.005, Table 4).  Since only one variable was significantly associated with intubation and ICU admission (one variable for each outcome), constructing a multivariate regression analysis for these outcomes was not applicable. Concerning the factors associated with death, results revealed that death was significantly lower among participants aged 45 to <60 compared to those aged 60 years or older (OR = 0.3, 95% CI, 0.1 to 0.9, p = 0.038). Furthermore, death was significantly higher among obese patients (OR = 3.0, 95% CI, 1.2 to 8.2, p = 0.027), as well as those who were admitted to the ICU (OR = 6.0, 95% CI, 1.6 to 8.0, p < 0.001) and intubated (OR = 5.3, 95% CI, 1.7 to 18.3, p < 0.001) ( Table 5).  The significantly associated variables were exclusively entered in a multivariate model to account for the independent association between the variables and the risk of death. To fulfill the assumptions of logistic regression, we assessed the risk of multicollinearity using the variance inflation factor (VIF), and we found no risk of multicollinearity (VIF < 5 for all independent variables). Additionally, we excluded one record which was deemed an influential outlier (with the absolute standardized error of >3, Figure 2).

FIGURE 2: A scatterplot of the standardized residuals of individual data to assess the potential influential data points.
In the final mode, the independent variables explained 59.8% of the variance in the risk of death. Only ICU admission was an antecedent risk factor for death among patients (OR = 4.9, 95% CI, 1.3 to 8.0, p < 0.001, Table 5).

Discussion
It is well established that obesity is a clinically important risk factor for severe COVID-19 leading to pneumonia or acute respiratory distress syndrome requiring intubation. Our objective was to investigate the impact of obesity on patients with COVID-19 who required hospitalization, a population particularly vulnerable to serious medical complications [14]. Our results were consistent with several previous reports showing that higher BMI is significantly associated with more severe COVID-19 disease, necessitating hospitalization [15,16].
An earlier study investigating obesity as a risk factor for severe COVID-19 reported that obese patients have altered immune cell activity compared to healthy-weight patients; this alteration of the host defense mechanism puts patients at increased risk of COVID-19 complications [17]. Moreover, a reservoir for viral replication and, therefore, increased viral shedding-can be found in the adipose tissue in obese patients, making them subsequently more susceptible to severe disease courses [18].
Obese patients also have a higher risk of respiratory failure than non-obese patients [19]. Our findings are consistent with previous reports that evaluated the impact of high BMI in hospitalized patients with COVID-19 [20][21][22][23]. Our results indicated that the higher the BMI, the higher the risk of intubation, as obese patients required intubation more than overweight patients. This finding could be attributed to a significant decrease in protective cardiopulmonary reserves in obese patients due to adaptation mechanisms in the respiratory system that cause an increase in airway resistance and reduce gas exchange. Further complicating matters, obese patients with COVID-19 have increased immune dysregulation and dysfunction that increase the risk of pneumonia and progression to critical illness and multiorgan failure [24,25].
Furthermore, our study demonstrates that being obese puts the patient at increased risk of death from COVID-19, as it showed that more obese patients died than overweight patients. As previously reported in several cohort studies, obesity is associated with several remarkable comorbidities, such as diabetes,