Comorbidities and COVID – What’s the Link?

by | Mar 18, 2021 | Health and Wellness, Immune System

It has been shown that several comorbidities – including hypertension, obesity and diabetes –  increase the risk for COVID-19 complications. Understanding why this relationship exists provides clues on how we can best improve our resistance to this virus.

The Link Between COVID-19 Infection and Comorbidities

It has been shown that several pre-existing conditions, known in the medical word as “comorbidities” can significantly increase a person’s risk of developing severe complications due to COVID-19. These comorbidities include hypertension, obesity, insulin resistance, diabetes and existing cardiac disease. Determining why and how these comorbidities increase a person’s risk of infection can shed some light on how we can best prepare our bodies and stay as healthy as possible if and when we are exposed.

It turns out that certain health conditions, including the comorbidities listed above, result in altered immune system function, which can include unhealthy forms of inflammation. Inflammation is a hallmark of immune system dysfunction and is strongly associated with COVID-19 infection.

So how do our immune systems become dysfunctional, and why are so many people affected? As it turns out, there is a condition called metabolic syndrome which is characterized by altered immune function. In fact, it overlaps with the comorbidities that contribute to COVID-19 severity, and the number of people suffering from metabolic syndrome has been increasing steadily over the past several decades. Technically, metabolic syndrome is not a disease; rather, it is better described as a state of lowered resilience to disease. People with metabolic syndrome are at increased risk to both non-communicable and infectious diseases such as COVID-19.

How Metabolic Syndrome and COVID-19 are Related

Before we dive in to how having metabolic syndrome can predispose a person to more severe COVID-19 infections, let’s first look at how COVID-19 affects the body. The high infection rate of COVID-19 and that it can be transmitted by asymptomatic individuals has been widely published. It also appears that virtually all body systems can be impacted by a COVID-19 infection, as serious cases of respiratory, cardiovascular, immunological, kidney, liver, gastrointestinal and neurological crises have all been reported. In the organ systems affected by COVID-19, cells have been found to express the angiotensin-converting enzyme 2 (ACE2) receptor. The ACE2 receptor is thought to represent a target for the virus which allows it to bind to and enter a person’s cells. Recent studies show that the virus binds to the ACE2 receptor more easily in the presence of inflammation.

The COVID-19 virus has spike-like proteins on its surface, which give the virus a unique ability to bind tightly to the ACE2 receptors. These spikes have what are called high affinity furin binding sites (furin is an enzyme in human blood). This enables the virus to hijack furin in the blood, which allows it to attach to the ACE2 receptors on tissues more readily and facilitate penetration into cells. This ability to hijack furin and strongly bind to the ACE2 receptor is what makes COVID-19 more infective than other coronaviruses.

Here’s where things get interesting; regulation of furin levels in the blood is influenced, in part, by the immune system and inflammation. In people that have comorbidities associated with metabolic syndrome (hypertension, obesity, insulin resistance and inflammation), furin levels have been found to be elevated, providing a direct route for both transmission and increased severity of infection for COVID-19.

Putting this all together: metabolic syndrome dramatically increases a person’s risk of developing comorbidities like hypertension and diabetes. These in turn predispose a person to contracting COVID-19 and for developing more severe infection. This is likely due to several factors, including the chronic inflammatory state associated with metabolic syndrome, increased levels of furin in the blood (which leads to increased binding of the virus to a person’s cells), and depressed immune function (which is characteristic of metabolic syndrome). For these reasons, when a person with one of the comorbidities associated with metabolic syndrome contracts COVID-19, the virus is presented with a host that is uniquely suited to allow it to infect nearly every cell in the body.

So What Can We Do?

Now that we know how and why metabolic syndrome are linked to COVID-19, the best and most logical step is to reduce the prevalence of metabolic syndrome, and there are a lot of known strategies that we can implement to achieve this end. The Mediterranean diet – which is high in fresh vegetables, fruits, whole grains, virgin olive oil, nuts, seeds and fish that are high in omega-3 fats, while being low in sugar, processed foods and alcohol – has been extensively studied for its positive influence on the comorbidities associated with metabolic syndrome and its ability to reduce chronic inflammation.

In addition, certain phytochemicals, such as the flavonoids quercetin and luteolin, have been found to bind to the ACE2 receptor on COVID-19, which can potentially help to protect against infection. Once more, a recent study evaluated how quercetin and vitamin D may contribute to the mitigation of COVID-19 through their impact on immune system function and the reduction of chronic inflammation.

Looking at the available research, it’s clear that improvements in the lifestyle, environmental and dietary factors associated with the comorbidities that are linked to both metabolic syndrome and COVID-19  can have a positive impact on enhancing immunity. Studies have shown that improved physical fitness, reduction in obesity, and increased quality of sleep can all positively influence immunity and reduce the severity of viral infection like COVID-19.

The silver lining as we head into our second year with COVID-19 is that much is known on how we can beat it. Slowing the spread – by wearing masks, social distancing and staying home if you’re sick – will help, but the real work comes in making the choices on a daily basis – by choosing to eat only health foods, getting daily exercise, incorporating daily stress management and getting enough good quality sleep – to improve our immune function so we are equipped to not only fight off COVID-19, but whatever other pathogens cross our paths as we live our lives to the fullest of our ability.

For those that are interested, in addition to the references below, Jeffrey Bland, PhD, has written a series on COVID-19 that offer some unique perspectives on this virus and how we should approach it.

References

  • Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. N Engl J Med. 2020 May 21;382(21):2012–2022.
  • Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, Clinical Course, and Outcomes of Critically Ill Adults With COVID-19 in New York City: A Prospective Cohort Study. Lancet. 2020 Jun 6;395(10239):1763–1770.
  • Rizzo P, Vieceli Dalla Sega F, Fortini F, et al. COVID-19 in the Heart and the Lungs: Could We “Notch” the Inflammatory Storm? Basic Res Cardiol. 2020 Apr 9;115(3):31.
  • Fuellen G, Liesenfeld O, Kowald A, et al. The Preventive Strategy for Pandemics in the Elderly Is to Collect in Advance Samples & Data to Counteract Chronic Inflammation (Inflammaging). Ageing Res Rev. 2020 May 23;101091.
  • Marhl M, Grubelnik V, Magdič M, Markovič R. Diabetes and Metabolic Syndrome as Risk Factors for COVID-19. Diabetes Metab Syndr. 2020 May 8;14(4):671–677.
  • Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020 Apr 15.
  • Brielle ES, Schneidman-Duhovny D, Linial M. The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting With the ACE2 Human Receptor. Viruses. 2020 Apr 30;12(5):E497.
  • Ziegler CGK, Allon SJ, Nyquist SK, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets Across Tissues. Cell. 2020 May 28;181(5):1016–1035.e19.
  • Hoffmann M, Kleine-Weber H, Pöhlmann S, et al. A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell. 2020 May 21;78(4):779–784.e5.
  • Wang Q, Zhang Y, Wu L, et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020 May 14;181(4):894–904.e9.
  • He Y, Ren L, Zhang Q, et al. Serum Furin as a Biomarker of High Blood Pressure: Findings From a Longitudinal Study in Chinese Adults. Hypertens Res. 2019 Nov;42(11):1808–1815.
  • Fernandez C, Rysä J, Almgren P, et al. Plasma Levels of the Proprotein Convertase Furin and Incidence of Diabetes and Mortality. J Intern Med. 2018 Oct;284(4):377–387.
  • Ueyama C, Horibe H, Yamase Y, et al. Association of FURIN and ZPR1 Polymorphisms With Metabolic Syndrome. Biomed Rep. 2015 Sep;3(5):641–647.
  • Serra-Majem L, Román-Viñas B, Sanchez-Villegas A, et al. Benefits of the Mediterranean Diet: Epidemiological and Molecular Aspects. Mol Aspects Med. 2019 Jun;67:1–55.
  • Smith M, Smith JC. Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface. 2020. ChemRxiv. 10.26434/chemrxiv.11871402.v4.
  • Yi L, Li Z, Yuan K, et al. Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus Into Host Cells. J Virol. 2004 Oct;78(20):11334–9.
  • Glinsky GV. Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines. 2020 May 21;8(5):129.
  • Jayawardena R, Sooriyaarachchi P, Chourdakis M, et al. Enhancing Immunity in Viral Infections, With Special Emphasis on COVID-19: A Review. Diabetes Metab Syndr. 2020 Apr 16;14(4):367–382.
  • Kenyon C. The Forrest Gump Approach to Preventing Severe COVID-19 — Reverse the Predisposing Pro-Inflammatory State With Exercise. Microbes Infect. May-Jun 2020;22(4–5):151–153.
  • Dixit S. Can Moderate Intensity Aerobic Exercise Be an Effective and Valuable Therapy in Preventing and Controlling the Pandemic of COVID-19? Med Hypotheses. 2020 May 20;143:109854.
  • Chiappetta S, Sharma AM, Bottino V, Stier C. COVID-19 and the Role of Chronic Inflammation in Patients With Obesity. Int J Obes (Lond). 2020 May 14;1–3.