key: cord-0893545-ey4yshwx authors: Chua, M; Zheng, SW title: Obesity and COVID-19: The Clash of Two Pandemics date: 2020-06-25 journal: Obes Res Clin Pract DOI: 10.1016/j.orcp.2020.06.003 sha: 05eec7af76b764e4122b524f36288b4207161b7d doc_id: 893545 cord_uid: ey4yshwx nan We present two cases for illustration and discussion. A 19-year-old male with no past medical history presented with a four-day history of fever, sore throat and myalgia. He had no cough, breathlessness or anosmia. Prior to illness, he had travelled to the United Kingdom, but had no sick contact. On initial assessment, the patient was febrile (temperature 39.6 degrees Celsius), hypertensive (blood pressure 152/89 mm Hg) and tachycardic (heart rate 102 beats per minute). Oxygen saturation was 100% on ambient air. He was obese (body weight 152 kilograms [kg], height 1.9 metres [m], body mass index (BMI) 44 kg/m 2 ). Physical examination was unremarkable. Investigations revealed normal white cell count, absolute lymphocyte count and lactate dehydrogenase (LDH) ( Table 1) . Chest X-ray (CXR) showed right midzone consolidation. Oropharyngeal swab was positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). The patient's clinical course was stormy. On his fourth hospitalization day, repeat CXR showed worsening bilateral opacities. Supplemental oxygen was required, and he was commenced on lopinavirritonavir. On the eighth hospitalization day, the patient had worsening type 1 respiratory failure and was transferred to the intensive care unit (ICU). He improved with highflow nasal oxygen, without need for mechanical ventilation. The duration of ICU and hospital stay was five and eighteen days respectively. J o u r n a l P r e -p r o o f An 18-year-old male with no past medical history presented with a one-week history of fever and dry cough. He had no recent contact or travel history. On initial assessment, the patient was afebrile (temperature 37.0 degrees Celsius). Blood pressure was 129/77 mm Hg, heart rate was 96 beats per minute and oxygen saturation on ambient air was 98%. He was obese (body weight 88.7 kg, height 1.73 m, BMI 30.7 kg/m 2 ). Physical examination was significant for right basal lung crepitations. Investigations revealed normal white cell count, absolute lymphocyte count and LDH with mildly elevated C-reactive protein ( Table 2) , while CXR showed bilateral consolidation. Oropharyngeal swab was positive for SARS-CoV-2 by RT-PCR. The patient remained clinically stable during his 7-day hospital stay. Older age (> 60 years old) and comorbidities such as diabetes mellitus (DM), hypertension, cardiovascular disease and chronic respiratory disease are well-established risk factors for severe COVID-19 1,2 . Our cases depict young patients with obesity and no other risk factors, who developed COVID-19 of at least moderate intensity 3 . Obesity was a risk factor for hospitalization and death during the 2009 H1N1 influenza pandemic 4 . Similarly, obesity is an increasingly recognized risk factor for severe and death, including in young patients [5] [6] [7] [8] [9] . According to the COVID-NET database in the United States of America, obesity is the second most common underlying condition amongst patients hospitalized with COVID-19, occurring in 59% of those 18 -49 years old 5 . In fact, it was more common than other described risk factors 1 such as DM (28.3%) and cardiovascular disease (27.8%) 5 . In a retrospective study of 3615 patients in New York, patients aged < 60 years with a BMI 30 -34.9 kg/m 2 and ≥ 35 kg/m 2 were 1.8 times and 3.6 times more likely to be admitted into critical care, compared to patients with BMI < 30 kg/m 2 6 . In another study by Simonnet et al, patients with BMI > 35 kg/m 2 were 7.36 times more likely to receive invasive mechanical ventilation compared to those with BMI < 25 kg/m 2 7 . These suggest a strong association between obesity and severe COVID-19. In the Asian context where the initial epicentre of the outbreak occurred, obesity has also been shown to be an important risk factor for severe COVID-19. In a study of 112 patients in Wuhan, China, the BMI of the patients admitted to ICU (25.5 kg/m 2 ) was significantly higher than those admitted to the general hospital (22.0 kg/m 2 ). The patients in this study were further divided into a non-survivor and survivor group. The percentage of patients with BMI > 25 kg/m 2 was significantly higher in the non-survivor group (88.2%) compared to the survivor group Obesity is closely linked to DM, hypertension and cardiovascular disease, aforementioned risk factors for severe COVID-19 1,2 . Physical inactivity, common in obesity, may lead to impaired immune response 10 . The altered dynamics of pulmonary ventilation with reduced diaphragmatic excursion and a relative increase in anatomical dead space may account for the increased incidence of severe COVID-19 in patients with obesity 10 . The presence of a pro-inflammatory state in obesity may impair immune response and pulmonary function 11 . Of particular interest is leptin, which is involved in weight regulation by decreasing energy intake and increasing energy expenditure; as well as modulation of the innate and adaptive immune function through activation of neutrophils, macrophages and T lymphocytes 11,12 . Leptin-deficient mice developed severe obesity and appeared to have increased susceptibility to infections 11 . Compared to mice of normal weight, obese mice with H1N1 influenza infection had higher leptin levels, increased interleukin-6 (IL-6), increased pulmonary viral titers and increased mortality; while administration of anti-leptin antibodies led to improved survival 13 . In humans, the rare condition of congenital leptin deficiency notwithstanding, obesity is typically characterized by hyperleptinemia and leptin resistance 12 . Indeed, the authors proposed that leptin was a co-factor for the 2009 H1N1 pandemic 13 An interesting observation is the association of obesity with lower Vitamin D serum levels 14 . As Vitamin D reduces the risk of viral infections through enhancing both innate and adaptive immunity 15 , this might contribute to increased risk of COVID-19 in people with obesity. Interestingly, Vitamin D also modulates the expression of angiotensin converting enzyme 2 (ACE-2), which is the putative co-receptor for cellular SARS-CoV-2 entry 16 . Increased adipose tissue in obesity could lead to increased ACE-2 expression and risk of infection 17 , although the link between ACE-2 and COVID-19 is currently unclear. The clash of these two pandemics carries significant implications. Obesity plays an important role in virus transmission. Adipose tissue may become a reservoir for SARS-CoV-2, leading to prolonged viral shedding, which has also been observed with other viruses including H1N1 influenza 10 . Obesity leads to poorer vaccination success and emergence of more virulent virus strains, due to blunted cytokine and interferon production 10 . In addition, people with obesity carry more infectious virus in exhaled breath due to higher ventilation volumes 10 Furthermore, novel agents investigated in clinical trials may require additional dose-optimizing studies in obese patients. The impact of COVID-19 extends beyond infected patients. Stay-at-home rules lead to increased sedentariness and consumption of processed, caloric-dense food. A major consequence is social isolation, which when added to social stigmatization due to obesity and pandemic-related stress, may increase psychosocial distress and maladaptive eating behaviours 20 . Virtual health tools such as telemedicine may be useful to reach out to this vulnerable group 20 . In summary, physicians should be aware of the far-reaching impact of the collision of the dual pandemicsobesity and COVID-19 18 . 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Leptin applications in 2015: what have we learned about leptin and obesity? Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with dietinduced obesity Vitamin D in obesity Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Considerations for obesity, vitamin D, and physical activity amidst the COVID-19 pandemic Risk of COVID-19 for patients with obesity COVID 19 and the Patient with Obesity -The Editors Speak Out Obesity and the risk and outcome of infection The Impact of COVID-19 on Bariatric Surgery: Re-Defining Psychosocial Care We confirm that none of the authors have a conflict of interest. We confirm that all authors had access to the data and participated in the preparation of this manuscript.We confirm that the authors did not receive any funding in the preparation of this manuscript.We confirm that the work described has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder. We have read and have abided by the statement of ethical standards for this manuscript which is submitted to the Obesity Research & Clinical Practice.