COVID-19 has been written about extensively since the start of 2020. And to everyone’s dismay, this topic won’t become outdated anytime soon. We talked about methods of physical prevention, economical upset, reorganization of the health system, vaccination, etc. But have we really taken into account the risk factors closely related to developing the severe form of COVID-19 requiring hospitalization and advanced health care, and how to reduce them? One thing is certain, even if the subject was raised briefly, few concrete strategies have been set in motion in our health system to allow people who wish to reduce their risk of developing complications related to COVID-19 to actually do so. In this article, I want to help you better understand the real impacts of your lifestyle on the health of your immune system in order to give you all the possible tools to take charge of your health despite the societal chaos that persists, and at a very low cost!

First, it is important to understand the very basic foundation of how our immune system works in order to realize the impact of our various behaviors on it. When we are exposed to a pathogen (virus, bacteria, fungus, etc.), the cells of our innate immune system (first line of defense) activate by recognizing the presence of a foreign microorganism in the body. They attack and try to weaken the latter in order to neutralize it and prevent the development of a more severe infection. These first-line cells also produce chemicals (cytokines) that act as a signal to alert other cells in our acquired immune system (second line of defense) to mobilize, i.e., the function of immunity which specializes in making antibodies that will be made to help destroy the pathogen unknown to the body.

In SARS-COV2 infection leading to the development of COVID-19, the immune system responds in the same way. However, it has long been wondered why there is such a great heterogenicity (diversity) in the presentation of the disease, that is, some people can eliminate the virus without even having developed symptoms (asymptomatic carriers), so that others are hospitalized in intensive care in a very unstable state. Physiologically, there are several reasons for this and here are the 3 main ones:

We note that the individuals who developed more severe complications showed a relative incompetence of their innate immune system (the body’s first line of defense) delaying the detection of the virus and by extension the attenuation of the warning signal to other immune cells from the body. Thus, the virus, having had a better capacity to reproduce without being neutralized at the right time, causes much more destruction in the body of its host before the latter can react adequately in its defense mechanisms. There are factors that can interfere with the effectiveness of frontline barriers and one of the most important is nutrition. Indeed, an individual who is malnourished and/or deficient in certain micronutrients will be more likely to have a poorly competent immune system.

We also note that complications related to infection with SARS-COV2 are more numerous in people suffering from chronic cardiometabolic diseases (cardiovascular diseases, diabetes, hypertension, obesity, etc.) in a worrying proportion. When you think about it, we see that the common denominator of these pathologies is … inflammation! This phenomenon testifies to the relative activation of the immune system under the effect of often unhealthy behaviors in order to protect the organism from these “repeated attacks” to its integrity (smoking, exposure to environmental toxins, ingestion of unhealthy processed foods, excessive secretions of stress hormones, etc.). This activation of the immune system does not make it more competent, quite the contrary. People with chronic illnesses are already seeing an increase in inflammatory cytokines (chemicals that alert the body to a broken defense), even before the virus infects them.

It is also important to mention that the SARS-COV2 virus makes it possible to infect the organism by binding its “spike” protein to the ACE2 receptors present on the surface of the cells of several organs of the body and particularly in the lungs, kidneys, intestines, brain, heart, etc. Immediately after its binding with the cell receptor, the virus can then enter the cell and use the cellular mechanics at its disposal to ensure its own replication, and thus, infect other cells with the virions (new viruses) produced, until the immune system tries to neutralize this process. In doing so, the infected cells are destroyed and are no longer functional to ensure their usual properties, thus leading to the multiple organ dysfunctions that we see appearing in cases of severe COVID-19 (respiratory failure, thrombosis, myocarditis, diarrhea, anosmia, etc.). However, this ACE2 receptor appears to have protective properties by being involved in certain enzymatic reactions regulating arterial pressure, vascular tone and the inflammatory state of blood vessels. It has been recognized that certain health conditions present in an individual can cause under-expression of ACE2 receptors on the surface of cells such as in hypertension, diabetes, cardiovascular disease, and in older people. Thus, the subsequent destruction of infected cells containing this ACE2 receptor, which has a beneficial and protective effect on the body, appears to be one of the factors contributing to the degree of severity of the attack from COVID-19 in this population. In addition, the destruction of ACE2 receptors is thought to be involved in the disproportionate inflammatory reaction that causes problems in the functioning of various organs, including the lungs.

When we talk about COVID-19, we fear what is called the “cytokine storm” that can cause a state of major instability in an individual and require hospitalization. These inflammatory cytokines, while they are present in our body for one essential reason, namely to stimulate the recruitment of immune cells involved in the body’s defense when it is faced with an attack, can cause many problems when they are present in too large a quantity: drop in pressure, drop in oxygenation, alteration of the contractility of the heart, inappropriate coagulation of blood in the veins and arteries, dysfunction of the kidneys and the liver, etc. The cytokine storm is therefore much more likely to occur in individuals who have an insufficient first-line barrier thus delaying detection of the virus and causing the immune system to overreact once it realizes the presence of the virus duplicated in the body, as well as in individuals who already have high inflammatory cytokines in their body due to their lifestyle (leading to chronic diseases that we know). It should be noted that the 2 mechanisms can coexist, making the situation of the patients concerned very worrying.

To save themselves from the potential complications of COVID-19, interventions on our health that can make a real difference go beyond good chronic disease control and/or systematic “prevention” supplementation or medication. It is not enough to NOT have a diagnosis of disease, because the metabolism can hide a whole different picture of vulnerability. On the contrary, it is necessary to act in a personalized way in order to reverse the physiological mechanisms possibly causing the chronic diseases that we know and ideally to determine and treat the existence of nutritional deficiencies that may be present in an individual according to their own behaviors. There is no “one size fits all” when it comes to prevention! The need to work with health professionals who are able to adapt recommendations to individual reality is paramount.

Among the main strategies for improving the inflammatory state and strengthening the first-line defenses, we find the following:

  1. Lose weight, especially the fat lying on the abdominal belt. It is well known that so-called “visceral” fat secretes a large amount of inflammatory cytokines. Being overweight is one of the most important risk factors for suffering from a severe form of COVID-19. In fact, nearly 75% of patients admitted to intensive care under the circumstances have a BMI of >25 and mortality is increased by 48%.
  2. Reverse insulin resistance by eating a lower carbohydrate diet. Hyperinsulinemia is a phenomenon that precedes the onset of diabetes by years or even decades. We see this metabolic peculiarity more and more in young people who have bad eating habits and it is exacerbated over time. Indeed, a diet rich in carbohydrates (as much that with a high glycemic load as that comprising foods with a high glycemic index) has a detrimental effect on the level of insulin in the blood which rises abnormally and constantly causing thus damage to the arteries and several key organs. Hyperinsulinemia is a major source of inflammation and is increasingly associated with cardiovascular disease.
  3. Get active every day, but avoid excess! Just because you run marathons or “Ironman” doesn’t mean you’re healthier than anyone else. On the contrary, too rigorous physical activities with little time to recover and/or insufficient nutrition can trigger an inflammatory process and poorer competence of the immune system. Conversely, sedentary individuals find themselves in such a metabolically deleterious situation. To optimize the positive effect on the immune system and inflammation, it is recommended to exercise at moderate intensity, at least 30 minutes per day (or 150 minutes/week).
  4. Eliminate stress from your daily life. Easier said than done in today’s society, but the strong link between chronic stress and long-term loss of immune system competence must be recognized. It is well demonstrated that in acute stress, the secreted stress hormones allow the adaptation of the organism in order to ensure its survival by different mechanisms and this is very desirable. However, when these hormones remain chronically high in the blood (what we see more and more with the way we manage our daily life which goes too quickly!), we notice a loss of effectiveness of the immune defense while contributing to keep inflammation levels high in the body. Relaxation exercises, meditation, social activities and contact with nature can help reduce stress.
  5. Promote quality sleep, ideally between 6 and 9 hours a night. Lack of sleep is undoubtedly one of the parameters that most influence the immune response. There was even a lower production of antibodies in people who did not sleep well the day before a vaccine was administered. It should also be kept in mind that the sleep which is artificially induced with certain “sleeping pills” type drugs can have a significantly affected architecture, making its restorative effect very little present.
  6. Encourage the growth of a healthy and balanced microbiome. We can never talk about it enough, but the microbiome that occupies the digestive tract can be considered an organ in itself because it has dynamic interactions with different bodily functions. You should know that nearly 70% of the immune cells in our body reside in our digestive system and several activation signals of these cells result from the metabolism of many substances by the microbiota. Consumption of fiber and foods containing probiotics, avoidance of refined sugar or processed foods, reduction of stress and great precaution in connection with medications consumed on a daily basis (for example, long-term antacids and antibiotics for non-infectious reasons) are elements that promote the growth of an optimal microbiota.
  7. Optimize nutritional status, in a personalized way. It is scandalous to realize that Canadians consume 60% of their calories in the form of ultra-processed foods, so the vitamin and mineral content are almost zero. Not to mention the increased consumption of various drugs that cause impaired absorption or increased excretion of several essential nutrients. You could almost say that the nutritional status of an obese individual sometimes resembles that of an individual in a state of chronic food deprivation. It is not uncommon to see additional nutritional deficiencies in those who drink alcohol, have problems with intestinal absorption, who eat little or are very selective, etc. We often hear about zinc, vitamin C and vitamin D which have a major impact on immune function, but several other micronutrients can be crucial in avoiding disrupting immune function in the event of a deficiency. Supplementation should be individualized on a case-by-case basis based on risk factors for developing a deficiency of various vitamins and minerals.

In conclusion, it can be realized that each individual has more power than they realize to successfully act on the risk factors that increase the likelihood of suffering from a severe form of COVID-19. Optimizing frontline defenses and its impact on the rest of the immune system to increase the ease with which the body can neutralize the virus as well as reducing systemic inflammation to decrease the risk of triggering a cytokine storm are important physiological elements to consider in the implementation of risk reduction strategies. COVID-19 will certainly have created significant societal chaos, but perhaps it will have allowed us to finally realize the strategies that allow to support health rather than to treat the disease once established? This is the power of personalized preventive medicine!

 

 

[1] Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):533-535. doi: 10.1038/s41423-020-0402-2. Epub 2020 Mar 19. PMID: 32203188; PMCID: PMC7091858.

2 Antonioli, L., Fornai, M., Pellegrini, C. et al. NKG2A and COVID-19: another brick in the wall. Cell Mol Immunol 17, 672–674 (2020). https://doi.org/10.1038/s41423-020-0450-7

3 Wu D, Lewis ED, Pae M, Meydani SN. Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance. Front Immunol. 2019;9:3160. Published 2019 Jan 15.  doi:10.3389/fimmu.2018.03160

4 Alyammahi SK, Abdin SM, Alhamad DW, Elgendy SM, Altell AT, Omar HA. The dynamic association between COVID-19 and chronic disorders: An updated insight into prevalence, mechanisms and therapeutic modalities. Infect Genet Evol. 2021;87:104647. doi:10.1016/j.meegid.2020.104647

5 Pahwa R, Goyal A, Bansal P, et al. Chronic Inflammation. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/

6 Strowig T, Henao-Mejia J, Elinav E, Flavell R. Inflammasomes in health and disease. Nature. 2012 Jan 18;481(7381):278-86. doi: 10.1038/nature10759. PMID: 22258606.

7 Kuba K, Imai Y, Ohto-Nakanishi T, Penninger JM. Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol Ther. 2010 Oct;128(1):119-28. doi: 10.1016/j.pharmthera.2010.06.003. Epub 2010 Jul 3. PMID: 20599443; PMCID: PMC7112678.

8 Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol. 2020 Jul;92(7):726-730. doi: 10.1002/jmv.25785. Epub 2020 Apr 5. PMID: 32221983; PMCID: PMC7317908.

9 Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76:14-20. doi:10.1016/j.ejim.2020.04.037

10 Popkin BM, Du S, Green WD, Beck MA, Algaith T, Herbst CH, Alsukait RF, Alluhidan M, Alazemi N, Shekar M. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes Rev. 2020 Nov;21(11):e13128. doi: 10.1111/obr.13128. Epub 2020 Aug 26. PMID: 32845580; PMCID: PMC7461480.

11 Li C, Ford ES, McGuire LC, Mokdad AH, Little RR, Reaven GM. Trends in hyperinsulinemia among nondiabetic adults in the U.S. Diabetes Care. 2006 Nov;29(11):2396-402. doi: 10.2337/dc06-0289. PMID: 17065674.

12 Gower BA, Pearson K, Bush N, Shikany JM, Howard VJ, Cohen CW, Tison SE, Howard G, Judd S. Diet pattern may affect fasting insulin in a large sample of black and white adults. Eur J Clin Nutr. 2021 Apr;75(4):628-635. doi: 10.1038/s41430-020-00762-9. Epub 2020 Oct 6. PMID: 33024285.

13 Dugani SB, Moorthy MV, Li C, et al. Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA Cardiol. Published online January 20, 2021. doi:10.1001/jamacardio.2020.7073

14 Lakier Smith L. Overtraining, excessive exercise, and altered immunity: is this a T helper-1 versus T helper-2 lymphocyte response? Sports Med. 2003;33(5):347-64. doi: 10.2165/00007256-200333050-00002. PMID: 12696983.

15 Ertek S, Cicero A. Impact of physical activity on inflammation: effects on cardiovascular disease risk and other inflammatory conditions. Arch Med Sci. 2012;8(5):794-804. doi:10.5114/aoms.2012.31614

16 Falconer CL, Cooper AR, Walhin JP, et al. Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes. Nutr Metab Cardiovasc Dis. 2014;24(9):956-962. doi:10.1016/j.numecd.2014.03.009

17 Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017 Apr;17(4):233-247. doi: 10.1038/nri.2017.1. Epub 2017 Feb 13. PMID: 28192415.

18 Hirotsu C, Tufik S, Andersen ML. Interactions between sleep, stress, and metabolism: From  physiological to pathological conditions. Sleep Sci. 2015;8(3):143-152. doi:10.1016/j.slsci.2015.09.002

19 Benedict C, Cedernaes J. Could a good night’s sleep improve COVID-19 vaccine efficacy? Lancet Respir Med. 2021 Mar 12:S2213-2600(21)00126-0. doi: 10.1016/S2213-2600(21)00126-0. Epub ahead of print. PMID: 33721558; PMCID: PMC7954467.

20 Lie JD, Tu KN, Shen DD, Wong BM. Pharmacological Treatment of Insomnia. P T. 2015;40(11):759-771.

21 Rooks, M., Garrett, W. Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16, 341–352 (2016). https://doi.org/10.1038/nri.2016.42

22 Blander JM, Longman RS, Iliev ID, Sonnenberg GF, Artis D. Regulation of inflammation by microbiota interactions with the host. Nature immunology, 18(8), 851–860.

23 https://www150.statcan.gc.ca/n1/pub/82-003-x/2020011/article/00001/tbl/tbl02-eng.htm

24 Butterfield S. Obesity and malnutrition are not mutually exclusive. Nutrition / ACP. February 2015. https://acphospitalist.org/archives/2015/02/nutrition.htm

25 Delafuente JC. Nutrients and immune responses. Rheum Dis Clin North Am. 1991 May;17(2):203-12. PMID: 1907394.