key: cord-1019504-3uiqs4ss
authors: Dutta, Nirjhar; Ingraham, Nicholas E.; Usher, Michael G.; Fox, Claudia; Tignanelli, Christopher J.; Bramante, Carolyn T.
title: We Should Do More to Offer Evidence-Based Treatment for an Important Modifiable Risk Factor for COVID-19: Obesity
date: 2021-03-01
journal: J Prim Care Community Health
DOI: 10.1177/2150132721996283
sha: c7186d045f44b3d71613cc2123fcfbe25f59c411
doc_id: 1019504
cord_uid: 3uiqs4ss

Observational studies, from multiple countries, repeatedly demonstrate an association between obesity and severe COVID-19, which is defined as need for hospitalization, intensive care unit admission, invasive mechanical ventilation (IMV) or death. Meta-analysis of studies from China, USA, and France show odds ratio (OR) of 2.31 (95% CI 1.3-4.1) for obesity and severe COVID-19. Other studies show OR of 12.1 (95% CI 3.25-45.1) for mortality and OR of 7.36 (95% CI 1.63-33.14) for need for IMV for patients with body mass index (BMI) ≥ 35 kg/m(2). Obesity is the only modifiable risk factor that is not routinely treated but treatment can lead to improvement in visceral adiposity, insulin sensitivity, and mortality risk. Increasing the awareness of the association between obesity and COVID-19 risk in the general population and medical community may serve as the impetus to make obesity identification and management a higher priority.

uncover a possible mechanistic pathway given the consistency of findings and dose-dependent relationship between BMI and poor outcomes from COVID- 19. There is biological plausibility to the observational data that suggest obesity leads to worse outcomes in COVID-19. Adipocytes, specifically visceral adipocytes, release inflammatory and coagulopathic mediators that contribute to COVID-19, including interleukins (IL-6, IL-8), C-reactive protein (CRP), tumor-necrosis-factor-alpha (TNF-alpha), angiotensinogen, plasminogen activated inhibitor-1, chemokine (C-C motif) ligand 2, D-dimer, lipoprotein lipase, compliment C5a, and lactic acid. [18] [19] [20] [21] [22] Patients with high adiposity may also be more susceptible to COVID-19 because levels of human angiotensin-converting enzyme 2 (ACE2), which is a binding site for the spike protein of SARS-CoV-2, 23 and may be higher in adipose tissue than lung tissue. 24 In addition to inflammatory and coagulopathic processes, there may be mechanical reasons for poor outcomes from COVID-19 in individuals with obesity. Obesity increases perfusion mismatching, shunting related to atelectasis, alveolar hypoventilation, and increased resting oxygen consumption, the combination of which may predispose to respiratory muscle inefficiency and precipitate respiratory failure. [25] [26] [27] As BMI increases, expiratory reserve volume and functional residual capacity decrease, with the greatest decrements seen between BMI 25 to 30 kg/m 2 and BMI 30 to 35 kg/m 2 , with very little additional change at higher BMIs. 28 This may explain the increased risk for invasive ventilation seen starting at a BMI of 25 kg/m 2 in patients in France, after controlling for comorbidities, 10 and the increased risk for ICU admission in young patients with a BMI starting at 30 kg/m 28 Male sex as a risk factor for poor outcomes from COVID-19 may be due to the that visceral adiposity rapidly accumulates at a lower BMI in men versus women. 29 Weight bias associated with obesity also contributes to poor outcomes: many healthcare providers (HCP) hold negative attitudes and stereotypes toward patients with obesity which impact their clinical decision making. [30] [31] [32] [33] [34] For example, many patients with obesity experience stress while seeking care which lead them to avoid or delay seeking care and have poor adherence to treatment due to mistrust of healthcare providers. 35, 36 Moreover, persons with obesity face structural stigma in healthcare settings in that many medical devices do not fit them. Additionally, moving individuals with high BMI's sometimes requires additional staff and specialized equipment and sometimes changing infrastructure such as wider doors and hallways; basic vital signs such as blood pressure may be inaccurate; obtaining diagnostic testing such as lab draws are harder and CT/MRI scanners may have size/weight limits and X-ray and ultrasound may be harder to interpret; even performing invasive procedures are harder because normal body landmarks are altered or harder to visualize; drug dosing and metabolism is altered. 37 Given the strong association noted with obesity and worse COVID-19 outcomes (and already known association of obesity with other chronic diseases such as hypertension, diabetes, coronary artery disease, cerebrovascular disease, and various types of cancer) and a biological mechanism for such outcomes, it is important to treat obesity as a serious disease. Obesity was defined as a disease by the American Medical Association in 2013, and this was an important first step in acknowledging it for what it is: a complex dysregulation of the body's energy regulatory systems, and not a person's behavioral faults. 38 We briefly outline the (overlapping) factors that lead to dysregulation in the body's energy regulatory system, most of which is outside of any individual's control: 39 1. Orexigenic signaling by second-order neurons is affected by epigenetic influences on intrauterine environment, including maternal BMI and stress; genetic influences; early life stress; early patterning and imprinting around food, including parental use of food as reward, punishment.

affected by modern macroenvironmental influences, including built environment, social structure, and cues. 3. Satiety signaling between the gut and limbic system and higher cortical centers are influenced by microenvironmental factors including sleep, circadian rhythm, stress, activity, nutrition. 40 4. Anorexigenic signaling by the limbic system is affected by gut microbiome, influenced by type of birth and early life antibiotic exposure.

Obesity Medicine is an emerging field of patient care. 41 While professional guidelines differ on whether obesity should be treated in the absence of common obesity-related comorbidities, 42,43 COVID-19 may shift this paradigm, as persons with obesity are at the highest risk of IMV or death. [8] [9] [10] [11] [12] [13] [14] [15] [16] In patients with obesity, just a 5% total body weight loss is associated with improved insulin sensitivity in adipose tissue, muscle, liver, improved pancreatic beta cell function, decrease visceral adiposity, as well as healthful changes in adipose tissue such as reduction in reactive oxygen species. 44 For patients with obesity, weight loss in adulthood may lead to 54% reduction in mortality (HR 0.46, 95% CI 0.27-0.22) compared to those who do not lose weight. 45 Evidence-based effective treatment of obesity include behavior change approaches to dietary pattern and physical activity, self-monitoring, improved sleep quality and quantity, anti-obesity pharmacotherapy, reduction of weight-gain promoting medications, endoscopic procedures, and bariatric surgery. 43, 46 Experienced obesity medicine clinicians often combine lifestyle approaches and several anti-obesity medications, and good follow-up, in the same patient, thus achieving far greater weight losses than are shown in any of the RCT's assessing any single antiobesity medication. Patients can access evidence-based obesity treatment in every state, and can expect to lose a significant amount of weight in the first 6 to 12 months of engaging in treatment, which may improve outcomes if infected with the SARS-CoV-2 virus. 6, 41, [47] [48] [49] HCPs can use the 5As framework (Assess, Advise, Agree, Assist, and Arrange) to assess patient's current thoughts on considering weight loss. 50 Ideally, HCPs can build and coordinate a multidisciplinary team that can help patients achieve their healthy weight goals. 51 The societal stigma associated with obesity can be tackled with increased education among HCPs about biology, chronicity, and overall health impact of obesity. 52 HCPs should be encouraged to schedule follow-up visits focusing specifically on obesity and frequent follow-up visits for obesity are reimbursed. 7 Clinics, hospitals, and emergency medical services should ensure that there is infrastructure and equipment in place to be able to provide the same quality of care to patients with obesity as those without. For practicing HCPs interested in gaining additional training and certification in obesity, there is a relatively easy pathway through the American Board of Obesity Medicine. 53 Last but not the least, there is a critical need for improved education in caring for patients with obesity in medical school and residency. 54 The COVID-19 pandemic has made it clear that patients with obesity deserve treatment of this condition, even in the absence of other comorbidities, and the challenge for HCPs and health systems is to do this in a sensitive, patient-centered, and evidence-based way.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Nirjhar Dutta https://orcid.org/0000-0001-9066-6452 Nicholas E. Ingraham https://orcid.org/0000-0002-0292-0594

Serosurveillance and the COVID-19 epidemic in the US: undetected, uncertain, and out of control

Covid-19: risk factors for severe disease and death

Validation of body mass index (BMI)-related ICD-9-CM and ICD-10-CM administrative diagnosis codes recorded in US claims data

Validity of a claims-based diagnosis of obesity among medicare beneficiaries

Effects of education and experience on primary care providers' perspectives of obesity treatments during a pragmatic trial

Geographic availability of physicians certified by the American board of obesity medicine relative to obesity prevalence

Perceptions of barriers to effective obesity care: results from the National ACTION study

Obesity in patients younger than 60 years is a risk factor for Covid-19 hospital admission

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation

Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York city: prospective cohort study

Obesity is a risk factor for greater COVID-19 severity

Clinical characteristics and outcomes of 112 cardiovascular disease patients

Obesity is associated with severe forms of COVID-19

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

Obesity aggravates COVID-19: a systematic review and meta-analysis

Letter to the Editor: obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease

Medical consequences of obesity

Visceral adipose tissue is more strongly associated with insulin resistance than subcutaneous adipose tissue in Chinese subjects with pre-diabetes

The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance

Difficulties in diagnosing pulmonary embolism in the obese patient: a literature review

Immunomodulation in COVID-19

Understanding the renin-angiotensin-aldosterone-SARS-CoV-axis: a comprehensive review

Two things about COVID-19 might need attention

Regional distribution of pulmonary ventilation and perfusion in obesity

Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine

The impact of morbid obesity on oxygen cost of breathing (V˙o 2RESP) at rest

The effects of body mass index on lung volumes

Identification of sex-specific thresholds for accumulation of visceral adipose tissue in adults

Weight bias reduction in health professionals: a systematic review

Family physicians' practices and attitudes regarding care of extremely obese patients

Physician respect for patients with obesity

Weight bias internalization and health: a systematic review

Internalization of weight bias: implications for binge eating and emotional well-being. Obesity (Silver Spring, Md)

Impact of weight bias and stigma on quality of care and outcomes for patients with obesity

Diet drugs work: why won't doctors prescribe them?

The obesity problem in the US hospitals. The Hospitalist

Regarding obesity as a disease: evolving policies and their implications

A review of the neurobiology of obesity and the available pharmacotherapies

Pharmacological management of obesity: an endocrine society clinical practice guideline

Mechanisms, pathophysiology, and management of obesity

Behavioral weight loss interventions to prevent obesity-related morbidity and mortality in adults: US preventive services task force recommendation statement

AHA/ACC/ TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and The Obesity Society

Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity

Association of weight loss between early adulthood and midlife with all-cause mortality risk in the US

Evidence-based weight loss interventions: individualized treatment options to maximize patient outcomes

Geographic availabiliy of physicians certified by the American Board of Obesity Medicine Relative ot Obesity Prevalence

A protocol to deliver intensive behavioral therapy (IBT) for obesity in primary care settings: the MODEL-IBT program

Cardiovascular risks and benefits of medications used for weight loss

Dietary and behavioral approaches in the management of obesity

An evidence-based guide for obesity treatment in primary care

Brief intervention effective in reducing weight bias in medical students

The benefits of obesity medicine certification

The role of obesity training in medical school and residency on Bariatric Surgery Knowledge in Primary Care Physicians