key: cord-0944206-3co4iptz authors: Al Heialy, Saba; Yaseen Hachim, Mahmood; Yaseen Hachim, Ibrahim; Bin Naeem, Kashif; Hannawi, Haifa; Al Salmi, Issa; Hannawi, Suad title: Combination of obesity and co-morbidities leads to unfavorable outcomes in COVID-19 patients date: 2020-12-03 journal: Saudi J Biol Sci DOI: 10.1016/j.sjbs.2020.11.081 sha: 8572127728f3dc1decf24e7089a6d0c4b1dd35d9 doc_id: 944206 cord_uid: 3co4iptz Objective Obesity has been described as a significant independent risk factors of COVID-19. We aimed to study the association between obesity, co-morbidities and clinical outcomes of COVID-19. Methods Clinical data from 417 patients were collected retrospectively from the Al Kuwait Hospital, Ministry of Health and Prevention (MOHAP), Dubai, United Arab Emirates, who were admitted between March and June 2020. Patients were divided according to their body mass index (BMI). Various clinical outcomes were examined: presenting symptoms, severity, major co-morbidities, ICU admission, death, ventilation, ARDS, septic shock and laboratory parameters. Results The average BMI was 29 ± 6.2 kg/m2. BMI alone was not associated with the outcomes examined. However, class II obese patients had more co-morbidities compared to other groups. Hypertension was the most significant co-morbidity associated with obesity. Patients with BMI above the average BMI (29 kg/m2) and presence of underlying co-morbidities showed significant increase in admission to ICU compared to patients below 29 kg/m2 and underlying co-morbidities (21.7% Vs. 9.2%), ARDS development (21.7% Vs. 10.53%), need for ventilation (8.3% Vs. 1.3%), and mortality (10% Vs. 1.3%). Conclusions Our data suggests that presence of underlying co-morbidities and high BMI work synergistically to affect the clinical outcomes of COVID-19. The coronavirus disease 2019 , caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has swept through the globe since the first reports in Wuhan, China in January 2020. As of August 31, 2020, the number of confirmed COVID-19 cases is 25,100,000 and the death toll has reached 844,000. Researchers are racing to understand the virus and the risk factors that lead to a more severe outcome of COVID-19. Notably, the presence of the following risk factors have been described as important predictors of severity of COVID-19; diabetes, hypertension, age, cardiovascular disease and obesity (1) (2) (3) . Although most individuals who are infected by SARS-CoV-2 show mild to moderate symptoms such as cough, fever and sore throat, a significant minority, and especially individuals with the risk factors described above, show much more severe symptoms which can lead to critical illness and even death. Obesity, as defined by a body mass index (BMI) of ≥30 kg/m 2 , has gained attention as one of the most important risk factors associated with severe outcome of COVID-19 (2, 4) . In fact, studies in the United Kingdom have shown that areas with higher rates of overweight/obese individuals are associated with higher rates of mortality (5) . This association has been linked to the "cytokine storm" where SARS-CoV-2 infection leads to the release of pro-inflammatory cytokines with detrimental effects on various organs (6) . Obesity is now recognized as a proinflammatory state where cytokines such as IL-6 have been shown to contribute to the chronic low-grade inflammation (7) . Therefore, it is believed that the pro-inflammatory state of obesity is worsened upon SARS-CoV-2 infection. Conversely, there is also data suggesting that obesity, due to its chronic inflammatory status and constant immune activation, may be protective in instances such as pneumonia. This has been named the "obesity paradox" (8) . However, the association between COVID-19 and obesity remains relatively unknown. In a study in Italy, 21% of 482 patients with COVID-19 were classified as obese with a BMI>30 kg/m 2 . High BMI of 30-34.9 kg/m 2 was associated with increased risk of respiratory failure and admission to Intensive Care Unit (ICU). Moreover, a BMI >35 kg/m 2 was associated with increased death rates (9) . In the United Arab Emirates (UAE), obesity is a common health concern especially among young males. 27% and 30% of Emirati men are classified as overweight and obese, respectively compared to 23% and 10% among women (10) . With the quick lifestyle changes that have occurred in the last 30 years, the overweight/obesity rates have reached over 30%. Therefore, it would be of interest to see the association of obesity and COVID-19 outcomes among the infected population in the UAE. Although anecdotally there seems to be a correlation between obesity and death in the region, there are, to our knowledge, no studies in the Middle East which have assessed the outcomes of COVID-19 in relation to obesity. Therefore, this study aimed to study the effect of BMI on COVID-19 outcomes in infected patients in the UAE. Clinical data from 417 patients were collected retrospectively from the Al Kuwait Hospital, Chronic medical history (Table 1 ) was defined as presence of at least one chronic medical condition. Patients were initially divided into 3 groups according to their BMI: lean (BMI 18.5 -24.9 kg/m 2 ) (n=60), overweight (BMI 25 -29.9 kg/m 2 ) (n=159), obese (BMI 30.0 kg/m 2 and above) (n=115) . The patients were then further divided into the different classes of obesity, according to the Center for Disease Control (CDC) classification: class I (BMI of 30 -34.9 kg/m 2 ), class II (BMI of 35 -39.9 kg/m 2 ), class III (BMI of 40 kg/m 2 or higher) (11). Moreover, the average BMI for this study population was 29 (±6.2) kg/m 2 which was used as a cutoff value when comparing patients with and without co-morbidities. Laboratory tests analyses include the following parameters: (1) Independence was used to examine the association between categorical variables. After excluding the records with outlier or missing medical results, COVID-19 patients (n=286) were categorized according to their corresponding BMI with a total average BMI of 29±6.2 kg/m 2 . While dividing patients into normal and overweight/obese (BMI ≥25 kg/m 2 ) showed that 83% of the cohort are obese (Tables 1 and 2 Our results present the association between BMI and outcomes of COVID-19 in the UAE. To our knowledge, this is the first study of its kind in the Middle East and North Africa (MENA) region to examine this association. Previous studies have either examined BMI or comorbidties as risk factors. However, our study has looked at the effect of both BMI and comorbidities in parallel on clinical outcomes of COVID-19. Our data suggests that presence of underlying co-morbidities and high BMI work synergistically in COVID-19 resulting in more clinical complications. Obesity has emerged as one of the most significant risk factors for complications associated with COVID-19. Many countries around the world have reported that BMI ≥ 30 kg/m 2 predisposes individuals to severe outcomes in response to SARS-CoV-2 infection. In a study in Italy, patients with BMI between 30 and 34.9 kg/m 2 were at significantly increased risk of respiratory failure and of admission to ICU whereas risk of death was seen in patients with BMI ≥ 35 kg/m 2 (9). In our study, the patients examined were at high risk of severe outcomes of COVID-19 at lower BMI than reported in the previous studies. Moreover, our COVID-19 patients with BMI over 29 kg/m 2 (which was the average BMI) and presence of co-morbidities, such as CVD, HTN, DM, cancer, and CKD which have been associated with COVID-19 were at increased risk of developing ARDS, admission to ICU, need for ventilation as well as death compared to patients with co-morbidities and BMI less than 29 kg/m 2 . Therefore, the presence of comorbidities and obesity together are strongly associated with COVID-19 outcomes whereas the co-morbidities alone in patients with BMI less than 29 kg/m 2 are not associated with COVID-19 outcomes. This is interesting as other studies in centers across the globe have shown that risk factors such as diabetes and HTN have been shown to associate with COVID-19 outcomes, without adjustment carried out for the BMI as a cofounder . In a study on 5700 patients in New York City, 56.6% of patients had hypertension whereas 33.8% of them had diabetes (12) . However, it is important to note that 41.7% of patients had a BMI over 30 kg/m 2 . Diabetes and HTN were not assessed in relation to BMI. Our study is added to previous findings that describe BMI as an independent risk factor in COVID-19 outcomes. The same cohort of patients also showed that class I and class II obesity were associated with higher WCC compared to other groups and class III obesity. A previous study has shown that patients with higher WCC are more likely to be admitted to the ICU, require ventilation and have underlying chronic illnesses and have higher mortality rates (13) . In fact, our study shows that class II obese patients had higher percentage of overall chronic disease compared to normal, overweight, classes I and III obese patients. Interestingly, the class III obese patients were mostly female whereas in the other groups a majority of the patients were male. In a study by Jin et al, it was shown that male COVID-19 patients are at increased risk of developing severe complications due to SARS-CoV-2 infection compared to female patients (14) . It has been suggested that the distribution of fat in women may explain why obesity is not an independent risk factor in female patients. This was shown in a retrospective cohort study in a large integrated healthcare organization in Southern California where female COVID-19 patients had no increased risk of death in association with BMI (15) . Moreover, a study on the distribution of fat in relation to COVID-19 severity showed that visceral adipose tissue and upper abdominal circumference significantly increase the severity of COVID-19 (16) . However, when our COVID-19 patients were categorized into underweight, normal, overweight, obese class I, class II and class III, we noted that most COVID-19 patients were in the overweight category. Although there was no significant difference between COVID-19 outcomes and BMI, there was trend towards an increase in ARDS risk among overweight, class I and class II obese patients. It is for that reason that we further classified the patients in relation to the average BMI which is close to the cutoff for obesity. This is an interesting finding as being overweight is not classified as obese although often the terms are used interchangeably. It would seem that among the UAE patients most patients were overweight which follows the trend of the general population where 43% of expatriates are classified as overweight compared to 32% which are classified as obese (17) . In fact, in the context of ARDS, it has been shown that obesity and morbid obesity are associated with lower mortality (18) . Our data show that class III obese patients are not at increased risk of developing ARDS. Due to this, it has been questioned whether the" obesity paradox" may be validated (or invalidated) in COVID-19 where obese individuals, due to the chronic inflammation which may confer a protective environment, may be protected against severe outcomes of the disease (19) . Further investigations need to be done to conclude this theory. The absence of an association between BMI and parameters such as severity, admission to ICU and death highlight the importance of other factors such as the presence of co-morbidities in infected patients in the UAE. Interestingly, this study sheds light on the association between overweight/obese category and co-morbidities and emphasizes the need to monitor these patients although most attention has been focused on the obese and morbidly obese patients. Moreover, it is the first study on the association between BMI/co-morbidities in the MENA region. A limitation of this study is that only hospitalized patients were included, and it would be of interest to evaluate the association between BMI and hospitalization risk and outcomes in outpatients. PubMed Central PMCID: PMCPMC7136855 Lifesciences, from Directed Systems, and from Cheetah Medical outside the submitted work. Dr Grasselli reported personal fees and nonfinancial support from Getinge and from Biotest, personal fees from Thermofisher, grants and personal fees from Fisher&Paykel Dr Iotti reported personal fees from Hamilton Medical, from Getinge Italia, from Eurosets, from Intersurgical, and from Burke & Burke outside the submitted work. Dr Pesenti reported personal fees from Maquet, from Novalung/Xenios, from Baxter, and from Boehringer Ingelheim outside the submitted work Obesity is the comorbidity more strongly associated for Covid-19 in Mexico. A case-control study Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Obesity as a predictor for a poor prognosis of COVID-19: A systematic review Overweight, obesity, and risk of hospitalization for COVID-19: A community-based cohort study of adults in the United Kingdom Insight into the relationship between obesity-induced low-level chronic inflammation and COVID-19 infection The major inflammatory mediator interleukin-6 and obesity Obesity survival paradox in pneumonia: a metaanalysis How important is obesity as a risk factor for respiratory failure, intensive care admission and death in hospitalised COVID-19 patients? Results from a single Italian centre Incidence and risk factors of type 2 diabetes mellitus in an overweight and obese population: a long-term retrospective cohort study from a Gulf state Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the Clinical features in 52 patients with COVID-19 who have increased leukocyte count: a retrospective analysis Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Annals of internal medicine The role of visceral adiposity in the severity of COVID-19: Highlights from a unicenter cross-sectional pilot study in Germany Prevalence of overweight and obesity in United Arab Emirates Expatriates: the UAE National Diabetes and Lifestyle Study Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis Does Coronavirus Disease 2019 Disprove the Obesity Paradox in Acute Respiratory Distress Syndrome? Author contribution: All authors contributed equally to the data collection, analysis, manuscript preparation.