Effects of diet on COVID-19 outcomes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, causing the coronavirus disease 2019 (COVID-19) pandemic, with over 512 million cases and over 6.2 million deaths so far.

The often-unpredictable severity of the illness has defied attempts to predict COVID-19 outcomes, driving much research to identify factors that can mitigate the clinical manifestations of the infection.

A new study discusses the role of dietary factors in this area, concluding,

Optimal nutrition status remains an effective strategy for supporting and preserving a strong immune response that is ready to protect against infections.”

Introduction

Infection with this novel coronavirus leads to an intense immune response in a subset of people, who rapidly show evidence of hyper-inflammation on a systemic scale, causing rapid deterioration of the clinical condition. This is mediated by the detection of COVID-19 by macrophages and dendritic antigen-presenting cells that present the viral antigen peptides to CD4 T cells. This results in their switching to Th1 or Th2 cells, secreting antiviral gamma-interferons (IFN-γ) or eliciting an adaptive humoral response, respectively.

The Th1/Th2 balance is essential to viral clearance and clinical resolution, as well as the return of the body systems to normal. Dysregulation of this immune response can cause exhaustion of the T cells and heightened inflammatory cascades (the so-called cytokine storm), causing severe disease. The mechanism of such critical disease is vascular damage because of the immune response, causing acute respiratory distress syndrome (ARDS) and a high incidence of death.

The role of nutrition has been suggested by many earlier studies, and is relevant in the light of the reduced access to some foods because of case isolation, contact quarantine and lockdown restrictions. The current paper, published online in the journal Nutrients, reviews the state of current knowledge in this area.

Findings

The consumption of fresh fruits and vegetables, that are rich in anti-oxidants in the form of plant polyphenols, promotes the suppression of inflammatory reactions and oxidative stress. Fish is another source of antioxidants in the shape of vitamins and omega-3 fatty acids, which reduce cell membrane lipid oxidation and proinflammatory mediator concentrations.

The Mediterranean diet is thus associated with an adiponectin-mediated increase in insulin sensitivity and decrease in systemic inflammation, reduced blood pressure and better arterial compliance, with lower levels of blood glucose, cholesterol and other dangerous lipids. Inflammatory biomarkers such as C-reactive protein (CRP), interleukin-6 and interleukin-8 are also reduced.

Even more significantly, a Mediterranean diet reduced the risk of rhinitis, asthma and respiratory impairment, even producing an anti-oxidant effect in children with asthma who were exposed to atmospheric pollution. Studies have shown that this diet was associated with fewer deaths from COVID-19 in a dose-dependent manner, after compensating for factors like the socioeconomic status, housing and life satisfaction.

In contrast, the Western diet is high in refined sugar and saturated fats, and is associated with systemic inflammation. This is probably because of the activation of innate immune cells via the Toll-like receptor 4 (TLR4) which eventually dampens the innate and adaptive immune response via chronic inflammation and oxidative stress. The outcome is an immunocompromised state that makes the individual more prone to infections, as well as damage to multiple organs over time.

In fact, the Western diet is linked to higher numbers of macrophages in the lungs and increased airway inflammation, which acts with the impaired immune response to predispose to COVID-19 and other viral infections.

Several dietary constituents and supplements are found to be useful in improving COVID-19 outcomes. For instance, vitamin A levels are higher in those who recover from the infection. Vitamin D is an immunomodulator, strengthening the innate immune response while preventing dysregulated T cell responses. High levels of this vitamin may lead to improved physical fitness.

Regular supplementation of vitamin D has been linked to better outcomes from COVID-19, though the evidence is weak overall. Seasonal efficacy also appears to be a possibility, and further research will be needed.

Antioxidant activity exerted by vitamins C and E could protect against cardiovascular damage by free radicals and reactive oxygen species while reducing systemic inflammation via its suppressive effect on pro-inflammatory cytokines. This could not just modulate the immune response but also fortify the lung epithelium against injury. While these have been shown to be safe and well-tolerated, more evidence will be needed to support their routine supplementation in COVID-19 patients.

Glutathione is the primary antioxidant defense mechanism in cells, inhibiting inflammatory signaling mediated by NF-κB activation. This molecule is found at high levels in the lung fluid, protecting the epithelium against oxidative damage. Its deficiency is linked to a higher incidence of viral infections with more severe symptoms and worse outcomes.

Here again, promising early results need to be supported by larger studies before the therapeutic dosage can be arrived at.

Zinc and other trace elements are also linked to improved innate and acquired immune responses. For instance, zinc may strengthen the airway epithelial barrier, while its deficiency may predispose to viral infection by damaging the barrier. Zinc also promotes immune cell growth, maturation, and activation, while its immunomodulatory effects are valuable in preventing hyperinflammation.

In addition, zinc has antiviral effects, preventing viral replication as an anti-fusion factor and inhibiting important viral lifecycle functions. Zinc levels have been associated with a potential improvement in COVID-19 outcomes, though its existence as a part of the diet may make it difficult to determine therapeutic levels. Other studies have shown the potential efficacy of omega-3 fatty acids in this condition.

Traditional Chinese medicine (TCM) makes use of herbal therapies and has been used to treat illnesses and infectious outbreaks. This is attributable to its antiviral, antibacterial and anti-inflammatory activities. Multiple preparations are available, some of which have been adapted to treat COVID-19.

Probiotics are live microbes that form part of the diet, regulating the immune response by acting on interleukins and natural killer cells, as well as the differentiation of T cells. The interconnection between the gut and the lungs makes it important to understand how these microbes affect the immune response.

At present, there is some evidence that probiotics are useful in upper respiratory infections, but more research is required to validate their efficacy and safety in immunocompromised patients.

Implications

The findings of this review paper indicate the role of nutrients in preventing and managing COVID-`9. The superior health profile of the Mediterranean diet and the powerful benefits of multiple dietary supplements such as antioxidants, vitamin D, and probiotics, in terms of their immunomodulatory and anti-inflammatory effects, make it important to understand how supplementation with these molecules can help improve COVID-19 outcomes.

Further research in this field is necessary, along with a better insight into the action of TCM, to take advantage of these nutrients in developing a nutritional program that can help build up a strong immune response to prevent and clear infectious agents rapidly and effectively.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.