key: cord-354928-brliql4d
authors: Wang, Jian; Zhu, Li; Liu, Longgen; Zhao, Xiang‐an; Zhang, Zhaoping; Xue, Leyang; Yan, Xuebing; Huang, Songping; Li, Yang; Cheng, Juan; Zhang, Biao; Xu, Tianmin; Li, Chunyang; Ji, Fang; Ming, Fang; Zhao, Yun; Shao, Huaping; Sang, Dawen; Zhao, Haiyan; Guan, Xinying; Chen, Xiaobing; Chen, Yuxin; Issa, Rahma; Wei, Jie; Huang, Rui; Zhu, Chuanwu; Wu, Chao
title: Overweight and obesity are risks factors of severe illness in patients with COVID‐19
date: 2020-07-31
journal: Obesity (Silver Spring)
DOI: 10.1002/oby.22979
sha: 
doc_id: 354928
cord_uid: brliql4d

OBJECTIVE: We aimed to observe the clinical characteristics of coronavirus disease 2019 (COVID‐19) patients with overweight and obesity. METHODS: Consecutive COVID‐19 patients from 10 hospitals of Jiangsu province, China were enrolled. RESULTS: 297 COVID‐19 patients were included. 39.39% and 13.47% of patients were overweight and obese, respectively. The proportions of bilateral pneumonia (92.50% vs. 73.57%, P=0.033) and type 2 diabetes (17.50% vs. 3.57%, P=0.006) were higher in patients with obesity than lean patients. The proportions of severe illness in patients with overweight (12.82% vs. 2.86%, P=0.006) and obesity (25.00% vs. 2.86%, P<0.001) were significantly higher than lean patients. More patients with obesity developed respiratory failure (20.00% vs. 2.86%, P<0.001) and acute respiratory distress syndrome (5.00% vs. 0%, P=0.024) than lean patients. The median days of hospitalization were longer in patients with obesity than lean patients (17.00 days vs. 14.00 days, P=0.029). Overweight (OR 4.222, 95%CI 1.322‐13.476, P=0.015) and obesity (OR 9.216, 95% CI 2.581‐32.903, P=0.001) were independent risk factors of severe illness. Obesity (HR 6.607, 95% CI 1.955‐22.329, P=0.002) was an independent risk factor of respiratory failure. CONCLUSION: Overweight and obesity were independent risk factors of severe illness in COVID‐19 patients. More attention should be paid to these patients.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared as pandemic by the World Health Organization (1) . Although most of the SARS-CoV-2 infection typically leads to relatively mild symptoms, 287,399 patients still died globally up to May 13, 2020 (2) . Old age and comorbidities, such as hypertension, diabetes, and chronic respiratory disease, were identified as risk factors of poor outcomes for COVID-19 patients according previous studies (3, 4) . Obesity was regarded as a common risk factor to aggravate the severity of respiratory diseases, which was associated with poor prognosis in influenza A (H1N1) pulmonary infection (5, 6) . Animal experiments have found that obesity alters inflammatory and pathological responses in the lung during influenza (7) (8) (9) . Excessive adipose accumulation could result in insulin resistance, oxidative stress, chronic inflammation, and circulating nutrients abnormality (10, 11) . However, few studies have focused on the impacts of obesity on COVID-19.

A retrospective study enrolled 124 COVID-19 patients who were admitted to intensive care unit (ICU) showed more patients required invasive mechanical ventilation (IMV) therapy with increased body mass index (BMI) (12) . Another study found that COVID-19 patients who were aged <60 years with a BMI between 30-34 kg/m 2 had 2.0 and 1.8 times risk of admission to acute and critical care as compared with individuals with a BMI <30 kg/m 2 , respectively (13) . These studies suggested that obesity may be associated with the severity of COVID-19. However, several confounders such as age, the presence of comorbidities were not adjusted which might have impacted the results. Whether overweight and obesity are independent risk factors of severe COVID-19 requires further research. In addition, the sample sizes are relatively small in the previous studies (12, 13) .

This study aimed to investigate the clinical features of COVID-19 patients with overweight and obesity in a multi-center cohort of COVID-19 in Jiangsu province, China.

Between January 18, 2020 and February 26, 2020, three hundred and forty-two consecutive COVID-19 patients from 10 medical centers in 10 cities of Jiangsu, China were enrolled. All COVID-19 patients were diagnosed by clinical manifestations, chest

This article is protected by copyright. All rights reserved CT, and real-time polymerase chain reaction (RT-PCR) according to World Health Organization interim guidance and the Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5) (14, 15) . All COVID-19 patients were tested positive for SARS-CoV-2 by RT-PCR in throat swab specimens. The last followed-up date was February 29, 2020. The study was approved by the ethics review boards of these medical centers.

We retrospectively recorded the clinical characteristics, complications, and outcomes of patients by electronic medical record system. The computational formula of body mass index (BMI) was weight (kg) divided by height (m) squared. According to criterion of guidelines for prevention and control of overweight and obesity in Chinese adults, 24 kg/m 2 ≤ BMI <28 kg/m 2 and BMI ≥ 28 kg/m 2 was defined as overweight and obesity, respectively (16, 17) . Severe COVID-19 was defined according to the current guideline as follows: (1) respiratory frequency ≥30/min; (2) pulse oximeter oxygen saturation ≤93% at rest; (3) oxygenation index ≤300 mmHg (15) . Acute respiratory distress syndrome (ARDS) was defined according to the Berlin definition (18) .

Continuous variables were described as medians (interquartile range (IQR)) and categorical variables were presented as the counts and percentages. The independent group t tests (normal distribution) and Mann-Whitney U (non-normal distribution) were used to compared continuous variables between groups. Chi-square or Fisher exact test was used to compare the categorical variables. Multivariate logistic and cox regression analysis was used to adjust for confounding factors, including age, gender and comorbidities. P<0.05 was considered to be statistical significant. SPSS version 22.0 software (SPSS Inc., Chicago, IL, United States) was used for the analysis.

Thirty-four patients were excluded due to the lack of BMI data and 11 patients under 12 years old were also excluded. Eventually, two hundred and ninety-seven patients were enrolled in this study. The clinical characteristics were presented in Table 1 . Of the 297 COVID-19 patients, 117 (39.39%) and 40 (13.47%) patients were overweight (24 kg/m 2 ≤ Accepted Article BMI < 28 kg/m 2 ) and obesity (BMI ≥ 28 kg/m 2 ), respectively. The median age was 38.00 

The proportions of patients use of atomized inhalation of interferon α-2b (60.00%, 56.41%, and 57.50%, P=0.84), lopinavir-ritonavir (70.01%, 75.21%, and 80.00%, P=0.383), and arbidol (52.86%, 47.86%, and 52.50%, P=0.709) were comparable among three groups ( Table 2 

Logistic regression analysis was performed to identify the association between obesity and severe illness ( 

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The associated factors of respiratory failure in COVID-19 patients were analyzed by cox regression analysis ( 

Overweight and obesity are serious global health problems (19, 20) . The global prevalence ratios of overweight and obesity are 38.5%-39.4% and 10.1%-14.8% respectively in the general population (21) . In our study, 39.39% and 13.47% of the COVID-19 patients were overweight and obese, respectively, suggesting that overweight and obesity may be not susceptible factors of COVID-19.

In our study, the most common symptoms were fever and cough, which were similar with previous studies (22, 23) . However, there were no significant differences in clinical symptoms among patients with different BMI. Patients with obesity had higher FBG levels and higher proportion of type 2 diabetes indicating that obesity was associated with an increased risk of type 2 diabetes. Several studies have demonstrated that the presence of type 2 diabetes was a significant risk factor of severe illness and fatal outcome of COVID-19 (24) (25) (26) . Thus, the association between the obesity-related comorbidities and severe COVID-19 deserves further investigation.

In our study, more patients with obesity had bilateral pneumonia compared to lean patients. In the report by Cai et al, among 383 COVID-19 patients from Shenzhen, China, obesity was also associated with a higher risk of severe pneumonia compared with lean patients (27) . More patients with overweight and obesity received oxygen therapy and non-IMV in the present study. Our results revealed that overweight and obesity were risk factors of severe illness and more likely to developed complications such as respiratory failure and ARDS. After adjusting the confounding factors such as age and sex, overweight and obesity were still independent risk factors of severe illness of COVID-19.

Taken together, these results suggested that overweight and obesity were independently associated with the severity of COVID-19.

However, the mechanisms of overweight and obesity contributing to severe COVID-19

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are not yet defined. Obesity was regarded as a risk factor of severe illness and poor prognosis in many infectious diseases (28) . Obesity induces systematically chronic inflammation by increasing the secretion of cytokines such as interleukin 6, interleukin 8 and TNF-α, which may aggravate the injury of lung parenchyma and bronchi (29) (30) (31) .

Previous study also found that obesity might impair adaptive immune responses in influenza virus infection (32) . A similar mechanism might exist in COVID-19 patients. In addition, obesity causes a decrease in protective cardiorespiratory reserve and immune dysfunction (33) . Sattar et al also reported obesity could increase the risk of thrombosis, which is an unignorable risk factor of severe COVID-19 (33) . With regards to lung function, obesity reduce expiratory volume and forced vital capacity (33) (34) (35) . In addition, animal models demonstrated that obesity leads to decreased natural killer cell cytotoxicity and increased mortality in influenza infection (36) . However, the mechanisms of overweight and obesity in the severity of COVID-19 deserve further investigation.

There were several limitations in our study. Firstly, the outcomes of the COVID-19 patients had relative favorable outcomes with no death patients. Thus, we could not analyze the association of overweight/obesity and fatal outcome in COVID-19 patients.

Secondly, the associations of overweight/obesity with IMV could not be analyzed either.

However, Kalligeros et al reported the potential association of obesity with severe outcomes in 102 patients hospitalized with COVID-19 (37) . They found that obesity was independently associated with the use of IMV (37) . Thirdly, many of the treatments and outcomes (oxygen therapy, non-IMV, admission to ICU, days of hospitalization) are subject to bias from clinicians who were in charge for the management of patients.

Fourthly, our study was conducted later in the pandemic and by this point people had suspicions and some studies were already conducted on the topic that overweight and obesity were risk factors for more severe COVID-19 outcomes. Thus, the clinicians in charge of care might have just been overly cautious which might have biased our results.

Furthermore, we could not include all the patients in our province. Thus, there is a potential selection bias in our study. However, nearly half of the confirmed cases in our province were included in our present study. We consider that our study is representative. Finally, the impacts of overweight and obesity on the long-term outcomes of COVID-19 patients remain unclear.

In conclusion, COVID-19 patients with overweight and obesity had higher risks of severe

This article is protected by copyright. All rights reserved illness. Therefore, more attention should be paid to COVID-19 patients with overweight or obesity. However, more studies are needed to confirm our findings and to reveal the underlying mechanisms of overweight and obesity associated with higher risks of severe illness in COVID-19. 

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