The Obesity-COVID19 Link

Dr George Cho MFSc CEP ND
Clinic Director, Pathways Lifestyle Medicine Clinics
Medical Director, Lifestyle is Medicine
Certified Exercise Physiologist, Cleveland Clinic Canada

As more research on the COVID-19 pandemic emerges, a very interesting observation is being noted by researchers: obesity makes COVID-19 worse.  Scientific papers are noting that excess weight is associated with greater risk of being admitted to ICU, needing ventilators and even dying from COVID-19. For example, in a French university hospital, they found that 81.8% of severely obese COVID-19 patients needed invasive ventilation compared to 58.1% of lean patients (1). In Italy, they collected data on all patients coming into one particular hospital for the month of March and found that 31% of patients needing  intensive care were obese (2).  On top of this, they found that 58.1% of the patients needed intensive care were overweight (2). This means nearly 90% of those who were admitted to ICU due to COVID-19 had excess weight (2). Other researchers have calculated that being overweight increased the risk of needing a ventilator by 69% (3). However, this number jumps drastically to 245% for obesity stage 1 and a staggering 636% increased risk of needing a ventilator for those who are severely obese (BMI greater than 35) (3).

In New York, 41.7% of hospitalized patients were obese according to one report (4). This is not including overweight people. In a different report looking at patients in New York, the odds of needing intensive care, ventilator support, admission to hospice care or even death, increased by 73% in those who were obese (5).

Why is obesity an issue with COVID-19?

These statistics may be a source of confusion to many since obesity and infections are not seen as being related. But when one considers the underlying physiology, it becomes very easy to understand why excess fat is associated with worse outcomes from an infection like SARS-CoV-2.

Cytokine storm

To make sense of this, it is helpful to understand what exactly is going on inside an individual infected with SARS CoV-2 as they progress to a severe form of COVID-19. In order to do this, we must look at a process called: cytokines storm.

When people are infected with SARS-CoV-2, the immune system tries to mount a response, but if the immune system is dysregulated (not balanced between anti and pro-inflammatory components), then it may actually over-respond. It does so by releasing a very large number of protein messengers called cytokines. This massive release of cytokines is called: cytokines storm. They have noticed that increased levels of cytokines consistent with what would be expected in cytokine storm, seem to be present in severe COVID-19 (6, 7, 8).

Cytokines are messengers that signal the immune cells to activate (9). This may sound like a good thing; more immune cells to kill off the infection, right? However, if a massive number of cytokines are released in a pro-inflammatory, dysregulated environment, then it sets off a whole series of events that may actually be detrimental, not beneficial. A hyper-activated immune system results in very high levels of inflammation which may lead to collateral damage to the lung cells as the immune cells desperately attempts to fight the virus (10). The result is that lung tissue may actually become damaged (15).

Another consequence is pulmonary fibrosis. Fibrosis means hardening of the tissues. Pulmonary fibrosis therefore means hardening of the lung tissues. Fibrosis occurs in response to injury. We can see it like the body’s attempt to “patch up” damage.  However, in the lungs, this is generally not a good thing since the lungs need to be able to expand and contract, but if it becomes hard, then this essential function becomes limited. Lung damage and hardening more difficulty transporting oxygen which leads to the COVID-19 patient needing a ventilator. In severe COVID-19, pulmonary fibrosis is likely occurring as a result of cytokine storm (15).

Thus, it is important to note that a hyper-active immune system is not always desirable. Rather a highly regulated, balanced immune system is the optimal immune state to aim for.

Obesity is pro-inflammatory state

Keeping this in mind, let’s turn to obesity. Fat cells (adipose tissue) are not dormant cells, they do not just sit there doing nothing. On the contrary, fat cells are very metabolically active. When it comes to the immune system, unfortunately, fat cells are pro-inflammatory (promotes inflammation), and are characterized by a state of immune dysregulation (11, 12). What does this mean? There is an imbalance between anti-inflammatory and pro-inflammatory immune components (12). Some suggest that in fat cells, there are certain inflammatory cytokine programs that are preactivated (13).

To make matters worse, the receptor that SARS CoV-2 uses to penetrate into cells (the angiotensin-converting enzyme 2 receptor) is present in adipose tissue (12 -15). Thus, in an obese state, there is:

Preactivated inflammatory cytokines + more receptors for SARS-CoV-2 entry.

This is a recipe for disaster.

If a virus like SARS-CoV-2 penetrates a tissue that is already susceptible to high levels of inflammation, then it is easy to see how this can cause the aforementioned cytokine storm and set off the cascade of events resulting in patients having such a difficult time breathing that a ventilator becomes necessary.

Healthy lifestyle habits are critical

As is well known, being physically active and clean, healthy nutrition are indispensable components of preventing the build-up of excess fat tissue in our bodies. Even switching from very little activity to a moderate level of physical activity can lower the risk of obesity by 30% (16). For those who may already be carrying excess fat, exercising plus a very healthy eating pattern will be helpful (17).

Healthy nutrition is essential. Massively limiting processed foods is the most important step. After this, it is eating plant-based. Seventh-day Adventists who are plant-based tend to have lower rates of obesity. (18)

The COVID-19 pandemic is another example why maintaining a healthy weight is so critical. The reality is that people can survive this virus. However, if our bodies are not unhealthy and carrying excess fat, it turns a would-be survivor into a potential death. If there ever was a wake-up call to get physically active, eat healthy, and share the health message, the COVID-19 saga ought to be it.  

References

1.  Caussey, C et al. Obesity is associated with severe forms of COVID-19. Obesity. 2020 Apr 21. doi: 1002/oby.228

2.  Barrasa, H. et al. SARS-CoV-2 in Spanish Intensive Care: Early experience with 15-day survival in Vitoria. Anaesthesia Critical Care and Pain Medicine (2020), doi:https://doi.org/10.1016/j.accpm.2020.04.001

3.  Simonnet, A et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity. (2020). Doi: 10.1002/oby.22831

4.  Richardson, S et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19  in the New York City area. JAMA. 2020. Doi: 10.1001/jama.2020.6775

5.  Petrilli, C et al. Factors associated with hospitalization and critical illness among 4103 patients with Covid-19 disease in New York city. medRxic. (2020)

6.  Zhao, M. Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies. Int j Antimicrob Agents. 2020 apr 16; 105982

7.  Huang, C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Feb 15; 395 (10223): 497 - 506

8.  Chen, G et al. Clinicall and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130 (5): 2620 - 2629

9.  Kany, S et al. Cytokines in inflammatory disease. Int J Mol Sci 2019, 20, 6008

10. Yuki, K et al. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Apr 20; 215:108427

11. Sattar, N et al. Obesity a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation. 2020 Apr 22. Doi: 10.1161/circulationaha.120.047659

12. Malavazos, A et al. Targeting the adipose tissue in COVID-19. Obesity. 2020 Apr 12

13. Ryan, P & Caplice, N. Is adipose tissue a reservoir for viral spread, immune activation and cytokine amplification in Covid-19. Obesity. 2020 Apr 21. Doi: 10.1002/oby.22843.

14. Kassir, R. Risk of COVID-19 for patients with obesity. Obes Rev. 2020 Apr 13. doi: 1111/obr.13034

15. Kruglikov, I & Scherer, P. The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections. Obesity. 2020 Apr 27. doi: 10.1002/oby.22856

16. Leskinen, T et al. Change in physical activity and accumulation of cardiometabolic risk factors. Preventive Medicine. 112 92018) 31 – 37

17. Chin, SH et al. Physical activity and obesity: What we know and what we need to know. Obes Rev. 2016 Dec ; 17 (12): 1226 - 1244

18. Fraser, G. Vegetarian diets: what do we know of their effects on common chronic diseases?  Am J Clin Nutr 2009; 89 (suppl): 1607 – 12S