Immunonutrition, COVID-19, and Obesity. Part 1.

This current year, we are still dealing with two global pandemics: obesity and, despite the new hope that vaccination brings, COVID-19. Previous literature has reported that obesity, characterized by elevated fat mass, can negatively impact immune system functionality. Consequently, this factor increases the risk of infection and complicates the recovery due to the high amounts of pro-inflammatory cytokines secreted by the adipocytes. New hypotheses have risen from this phenomenon, and between them, the use of immunonutrition is postulated to support immune function and decrease the inflammatory response. Furthermore, the use of pharmaconutrients like glutamine, zinc, omega-3 fatty acids, Vitamin C, arginine, selenium, Vitamin D, probiotics, and Vitamin E can contribute to improving outcomes in COVID-19 obese patients.

COVID-19, obesity and immune response

As stated earlier, obesity characterizes by an excess of body fat. Also, it is a multifactorial disease in which endocrine, socioeconomic, lifestyle habits, nutritional intake, and genetic factors complicate this condition. 

The basis of obesity condition is “adiposopathy.” The definition of adiposopathy is the pathological dysfunction of fatty tissue, both anatomical and functional. Furthermore, this dysfunctional adipose tissue occurs in the presence of adipocyte hypertrophy and visceral fat accumulation. In turn, this results in an overproduction of pro-inflammatory components contributing to the genesis of metabolic disorders. 

Nevertheless, this pro-inflammatory milieu also affects adipocyte’s immune mediation. Indeed, adipose tissue has the potential to manage adaptive and innate immune responses. In the context of obesity, the inflammatory milieu promotes a macrophage increment in the adipose tissue. Consequently, this alters adipocyte function, stimulating the secretion of inflammatory mediators, activating an elevated immune response, and a decrease of protective anti-inflammatory agents.

• COVID-19:

The presence of COVID-19 potentiates the cytokine storm, and it has been extensively reported. Indeed, more than 50 adipokines are present in this condition. Within them, leptin, adiponectin, IL-6, and TNF-a promote 

Leptin:

Leptin is an adipocyte-produced hormone that controls energy metabolism by multiple regulatory effects. As the leptin receptor expresses overall the immune system, this hormone connects the metabolic and immune systems. In obesity and overnutrition, leptin promotes the inflammatory state, while in undernutrition, leptin suppresses the immune response.

Leptin resistance leads to hyperleptinemia and insulin resistance, which results in disruption of the T-cell function leading to suppression of the infection response.

IL-6:

IL-6 has a pleiotropic effect, as it can be beneficial in lean subjects acting as an anti-inflammatory cytokine or pro-inflammatory in obese patients. Recent studies have focused on treating SARS-CoV-2 with IL-6 inhibition strategies. However, more studies need to be done to confirm its function in COVID-19 treatment.

TNF-a:

Macrophages and other immune cells secrete TNF-a in the acute phase of inflammation. The obese patients diagnosed with COVID-19 show elevated concentrations of TNF-a, IL-2, and IL-6. Therefore, targeted strategies to decrease these inflammatory cytokines are needed to improve COVID-19 outcomes.

Adiponectin:

On the contrary to all the pro-inflammatory factors mentioned before, increased adiponectin levels can be favorable for the patient. Adiponectin is an anti-inflammatory adipokine. Its levels seem to rise in the presence of infectious diseases, such as COVID-19. 

Furthermore, adiponectin’s immune effect relies upon its capacity to reduce innate and adaptive immune cell proliferation by:

• Blocking the production of pro-inflammatory factors: TNF-a, IL-6, and IL-2.
• Promoting the secretion of IL-10, an anti-inflammatory cytokine.

The supplementation of omega-3 fatty acids promotes the protective effects of adiponectin on the patient’s diet. In this specific case, improving outcomes is once again associated with the patient’s diet quality. 

Another interesting immunonutrition application is probiotics. Indeed, probiotics and glutamine supplementation improves gut permeability and could potentially enhance anthropometric measures by lowering adiposity. 

The interaction between the metabolic and immune axis relies heavily on the quantity of fatty tissue. We never thought a global infectious pandemic would hit our community this hard. Nevertheless, it left us with a high level of awareness of how anthropometric measures can interact with the immune system and leave us exposed to new infections. The urgency in which we need to change our lifestyle is undeniable. However, if the condition presents, we can improve outcomes with immunonutrition. – Ana Paola Rodríguez Arciniega, MS

References:

Di Renzo, Laura et al. “COVID-19: Is there a role for immunonutrition in obese patient?.” Journal of translational medicine vol. 18,1 415. 7 Nov. 2020, doi:10.1186/s12967-020-02594-4