Risk Factors Associated With Obesity and Worsening COVID-19 Outcomes

Adipocytes and related cells contribute to the pathogenicity and disease process in patients with obesity with COVID-19. Adipose tissue, particularly abdominal adipose tissue, exerts endocrine activity, effectively functioning as an endocrine organ that interacts with other endocrine organs and the immune system as well as influencing metabolic function.18

Angiotensin-converting enzyme 2 is upregulated in individuals with obesity and diabetes; thus, adipose tissue may provide a target for the virus and serve as a viral reservoir.17,18 SARS-CoV-2 affinity for ACE2 appears to be 10 to 20 times higher than that of severe acute respiratory syndrome coronavirus.17

Adiponectin level is a predictor of mortality in critically ill patients with COVID-19.18,19 This has led some researchers to suggest therapeutically targeting adipose tissue directly to manage COVID-19.7


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Respiratory muscle strength is poor in patients with obesity despite the greater demand on respiratory muscles because of increased airway resistance and changes to chest wall mechanics.23 Quiet breathing accounts for 1% to 3% of oxygen consumption under normal conditions in individuals with a healthy weight but accounts for more than 14% of oxygen consumption in obese individuals.23 The stress of a respiratory infection further compounds the work required to breathe, putting these patients at increased risk for respiratory failure. Screening for respiratory muscle impairment in patients with obesity along with respiratory muscle training may help prevent serious complications.23

Because of these factors, patients with obesity are more likely to have decreased forced expiratory volume, forced vital capacity, functional capacity, and respiratory system compliance and increased respiratory dead space. Abdominal obesity impairs pulmonary function in the supine position. All these factors contribute to higher rates of invasive mechanical ventilation among patients with COVID-19 who are obese.24 This is compounded by the lack of clear guidelines for indication of invasive mechanical ventilation in SARS-CoV-224; therefore, various strategies are being implemented across hospitals.24 To prevent COVID-19 progression in patients with obesity with respiratory impairment, the monoclonal antibody tocilizumab — which binds to the IL-6 receptor and inhibits its activity — has been suggested.8

A case report from China involved a patient with obesity with COVID-19 who developed type 2 acute respiratory failure (hypoxia with hypercapnia).25 Although the patient recovered without progression to malignant obesity hypoventilation syndrome and the need for invasive mechanical ventilation, recovery was prolonged. Current guidelines for COVID-19 management fail to consider the increased risk for patients with obesity to develop type 2 respiratory failure and recommend earlier invasive ventilation therapy for these patients.25

Respiratory conditions, including asthma, obstructive sleep apnea, hypoventilation syndrome, and chronic obstructive bronchopathy, are common in obesity, causing increased susceptibility to infection, more rapid disease progression, greater rates of complications, and poorer outcomes.8

Vitamin D deficiency, which is common in obese individuals,8 impairs immune response and increases the infection risk. Vitamin D supplementation can normalize the balance of pro-inflammatory and anti-inflammatory cytokines, which prevents respiratory infections and reduces the complication risk in existing infections.8 Italy has among the highest rates of vitamin D deficiency in Europe, particularly in people with obesity, and it has been hypothesized that vitamin D deficiency may play a role in the link between obesity and higher rates of complications and mortality due to COVID-19.8

It is unknown whether diabetes increases COVID-19 complication risk independently of obesity and hypertension; however, diabetes is linked to increased morbidity and mortality in SARS-CoV.11 Mechanisms may include11:

  • Increased binding efficiency of the virus;
  • Decreased viral clearance;
  • Poor T cell function;
  • Increased susceptibility to hyper-inflammation, leading to cytokine storm; and
  • Presence of cardiovascular disease

Barriers to Diagnosis and Treatment of COVID-19 in Patients With Obesity

Early diagnosis of COVID-19 is key to effectively treating patients with obesity; however, barriers exist for diagnosing the virus in patients with obesity as well as in racial and ethnic minorities, populations that are also at greater risk for negative outcomes of COVID-19 (Table 3).26,27

Table 3. Risk Factors for Minorities With COVID-19

Racial and Ethnic Disparities26,27Risk Factors26,27
Inadequate nutritional educationObesity
Decreased access to healthy foodsPoor nutritional status
Decreased access to health careDiabetes
Living in a densely populated areaIncreased risk for exposure
Living in an area of lower socioeconomic statusLower testing rates; less access to health care

These disparities play out in COVID-19 hospitalization rates. Surveillance data from the Centers for Disease Control and Prevention show that, of hospitalizations in Michigan associated with laboratory-confirmed COVID-19 as of April 10, 2020, 33% were in Black patients whereas only 14% of this state’s population is Black.27 Changing the societal conditions that create these disparities can lessen infectious disease burden among minority communities and, by extension, the entire country.28

Certain factors of obesity hinder COVID-19 management:

  • Medical facilities not equipped to accommodate patients with severe obesity8
  • Obscured findings on pulmonary ultrasound because of excessive weight8
  • Obesity-related difficulties with intubation or catheterization procedures (eg, tracheal trauma from intubation attempts because of lack of glottis visibility, necessitating multiple attempts and the use of a bougie)29
  • Less effective influenza immunization in obese individuals, who show twice the risk for flu infections regardless of immunization status, could indicate less effective COVID-19 immunization for obese patients as well30

Chronic inflammation inhibits macrophage activity and is a causative factor behind poor vaccination success in obese individuals.19 Sedentary behavior also reduces macrophage activation and impairs feedback inhibition of proinflammatory cytokines.24