COVID-19 and obesity: links and risks

KEYWORDS:

• Obesity
• mortality
• prognosis
• severity
• COVID-19

Applicable to the fields of endocrinology, as well as for specialists in cardiovascular disease (CVD), obesity has numerous cardiometabolic unfavorable consequences. Obesity is by far the leading cause of type 2 diabetes mellitus (T2DM) [1] and plays a pivotal role to adversely influence the metabolism of plasma lipids, e.g., by increasing triglycerides, reducing the cardioprotective values of high-density lipoprotein cholesterol (HDL-C), and contributing to increased arterial blood pressure up to the level of hypertension (HTN) [2]. Because adipocytes release cytokines that stimulate the liver to produce C-reactive protein and many other pro-inflammatory mediators, systemic levels of inflammation are considerably increased with obesity [3]. Therefore, besides leading to metabolic syndrome and DM, obesity has led to an increase in almost all CVD, especially heart failure (HF), more so the HF with preserved ejection fraction (HFpEF), but also HTN, coronary heart disease, stroke, peripheral artery occlusive disease, and atrial fibrillation (AF) [4].

Coronavirus disease 2019, abbreviated as COVID-19 and caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is being defined as the worst pandemic of modern times [5]. Alarmingly, between 15% and 20% of SARS-CoV-2-positive individuals progress to a very severe form of the disease [6], characterized by interstitial pneumonia with the potential to develop into acute respiratory distress syndrome (ARDS), severe systemic inflammatory response syndrome, severe coagulopathy, and even death.

Although we and others have described an ‘obesity paradox,’ where individuals or patients with overweight and obesity with CVD seem to have a better short-term and medium-term prognosis compared with lean patients with the same CVD [7,8], there does not appear to be any obesity paradox with COVID-19. Certainly, currently available clinical information and clinical expertise have identified obesity, especially more severe forms of obesity, as one of the most common clinical risk factors for worse prognosis and high mortality in coronavirus disease or COVID-19 patients [9–11], and like HF, this is likely the case whether individuals with obesity are metabolically healthy or unhealthy.

There are numerous reasons why obesity may have adverse effects in COVID-19. SARS-CoV-2 penetrates human cells through binding with angiotensin-converting enzyme 2 (ACE2), which is exposed at the surface of many types of cells [12]. The populations with obesity often have severe insulin-resistant states and imbalanced activity of the renin–angiotensin–aldosterone system, which may be important in promoting more severe disease in COVID-19 [13]. Although ACE2 in lung tissue is felt to be a major entry site of the SARS-CoV-2, ACE2 expression in adipose tissue is reported to be even higher than in lung tissue, which makes the increased adipose tissue in more severe obesity extremely vulnerable to SARS-CoV-2 and COVID-19 [14].

Additionally, obesity is associated with more baseline restrictive pulmonary disease and hypoventilation, as well as low-grade systemic inflammation [15,16]. Adding to this pulmonary insufficiency is the fact that low cardiorespiratory fitness is often present in obesity and, along with adiposity, is a major risk factor for the development of HF, especially HFpEF, thus leading to an increased risk of pulmonary vascular congestion due to HF in obesity, especially in more severe forms of obesity [7,14,17].

COVID-19 is also often accompanied by a multisystem disease, and individuals with overweight and obesity at baseline have an increased prevalence of renal insufficiency and chronic kidney disease, leading to these patients having less renal reserve [15]. Besides having more CVDs, especially HF [7,14,17], patients with obesity also are particularly vulnerable to develop AF [16], which appears to be an additional risk factor in COVID-19. Obesity is also associated with a significant degree of endothelial dysfunction [17], and recent evidence indicates endothelial cell infection in COVID-19 [18] and adiposity may worsen the clinical course of the disease. The fact that individuals with obesity also have more CVDs and T2DM, both are risk factors for COVID-19 severity and mortality, makes obesity, especially, severe obesity, particularly ominous in COVID-19.

Several studies to-date have clearly demonstrated that obesity is leading to considerably worse COVID-19 disease, especially a greater risk of needing hospitalizations, mechanical ventilation due to acute respiratory failure, ARDS, and extensive coagulopathy, thus finally posing the patients at higher risk of death [8–10,19–21]. Certainly, clinicians need to be aware that COVID-19 patients with overweight or obesity may require more aggressive active monitoring and treatment, especially those with more severe forms of obesity. Although it is probably too late for the current crisis, efforts to prevent obesity progression to severe forms are needed in order to help improve prognosis in the next pandemic and/or an eventual new outbreak.

Expert Opinion

Certainly, clinicians need to be aware that COVID-19 patients with overweight or obesity may require more aggressive active monitoring and treatment, especially those with more severe forms of obesity. Although it is probably too late for the current crisis, efforts to prevent obesity progression to severe forms are needed in order to help improve prognosis in the next pandemic and/or an eventual new outbreak.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

Fabian Sanchis-Gomar is supported by a postdoctoral contract granted by ‘Subprograma Atracció de Talent – Contractes Postdoctorals de la Universitat de València.’

Additional information

Funding

This paper was not funded.