Evidence review: Micronutrient deficiencies and COVID-19
Micronutrient deficiencies can impair immune function and increase susceptibility to infectious disease and with certain population groups more likely to have micronutrient deficiencies these groups tend to suffer increased morbidity and mortality from infectious diseases.
Therefore researchers from the Global Centre for Nutrition and Health at St John’s Innovation Centre, Cambridge, UK, have created a review, published in BMJ Nutrition, Prevention and Health, explaining how deficiencies in different micronutrients may be making people more susceptible to COVID-19.
They say practitioners should make deficiencies a consideration in the screening process of COVID-19 patients, or when screening may be difficult or impractical, to ensure blanket treatment using the best practice guidelines.
"Correction of established micronutrient deficiencies, or in some cases assumed suboptimal status, has the potential to help support immune function and mitigate risk of infection," they conclude.
The researchers point out that in some cases it has been shown that aiming for micronutrient intakes higher than the recommended dietary allowance (RDA) may be warranted in certain key micronutrients for high-risk population groups. They argue that this should be a consideration for the screening and treatment process in clinical practice and also for public health risk communication.
The review outlines the benefits of individual micronutrients.
Vitamin A plays a role in the regulation of the innate immune response (through natural killer (NK) cells, macrophages and neutrophils) and cell-mediated immunity (through the growth and differentiation of B cells), explains the report. It is also active in humoral antibody immunity and in cytokine signalling, with a role in the inflammatory response as a result.
The report notes that, of particular relevance in the case of COVID-19 is its role in mucosal epithelium (skin and mucous membrane) integrity, which is compromised in vitamin A deficiency and leads to increased susceptibility to infection via the eyes, respiratory and gastrointestinal tract.
Vitamin C is an effective antioxidant due to its ability to readily donate electrons which enhances the activity and function of immune cells, white blood cell migration and leucocyte function via neutrophil and monocyte mobilisation.
The review states: "Deficiencies lead to impaired immunity and higher susceptibility to infection, increasing the risk of contracting pneumonia and also enhancing disease severity.
"Dysfunctional epithelial barrier function of the lungs of animals has been shown to be restored by vitamin C administration. Supplementation is effective in both prevention and treatment of RTIs, having been shown to reduce incidence and duration of upper respiratory tract infection (URTI) and severity of pneumonia in hospitalised older adults as well as symptoms of common cold."
Vitamin D plays an important role in the innate immune system, through the production of antimicrobial peptides, including cathelicidin and defensins, the report states.
Observational data suggests a longstanding association between vitamin D status and the incidence of airway infection, in particular indicating a strong relationship between low status and the susceptibility to RTIs.
The review explains: "This process is highly dependent on the status of tissues, which stimulate immune antibacterial activity in a variety of cell types by increasing the production of antimicrobial factors and by enhancing mechanisms associated with autophagy.
"Many cell types express vitamin D receptors, with particularly high levels existing in lung epithelial cells. Deletion has the potential to increasing lung permeability and reduce pulmonary barrier integrity.
"The activation of vitamin D in the lung has the potential to induce these antimicrobials and attenuate inflammatory cytokines in response to viruses.
"Meta analyses of randomised controlled trials (RCTs) have shown that vitamin D supplementation significantly reduces the incidence of RTIs, with baseline status and dosing frequency found to be independent modifiers of risk."
Vitamin E protects the integrity of cell membranes from damage caused by free radicals and has the potential to influence both innate and adaptive immunity, the review states.
"Trial data on the effects of supplementation with vitamin E have been mixed, although has proven effective in reducing URTI in elderly care home residents. Improvements in innate NK cell response has also been shown with supplementation."
Selenium influences the immune response largely through its action in selenoproteins, which function as cellular antioxidants.
"Deficiency appears to enhance virulence or progression of some viral infections as evidenced by the relationship between Keshan disease, coxsackievirus B3 and influenza A, which are exacerbated by low Se status," the review states.
"Selenium also has an important role in the modulation of the inflammatory response and cytokine production. Supplementation of selenium improves the immune system response to viruses in deficient individuals. Although scarce evidence of this has been demonstrated in humans, limited studies have shown functional outcomes of selenium supplementation on the human immune system."
The authors add caution, noting the adverse effects of selenium in high status and it is suggested those who are selenium sufficient should not supplement due to potential adverse effects.
There is little zinc storage in the body, meaning that inadequate intakes can lead to deficiency, which is associated with compromised immune function.
The review explains that the role of zinc is complicated by the fact that pathogens require zinc to thrive, while the immune system also requires it to function, meaning status can appear to have a contradictory role in the infection process.
"Higher status (>70 mg/dL) can be predictive of favourable pneumonia incidence and treatment course in the institutionalised elderly, which is an important consideration given that they are a high-risk group for deficiency," it states.
"Numerous RCTs have demonstrated that supplementation of moderate zinc doses in healthy elderly individuals improves several aspects of immune functioning and may reduce incidence of infections and even overall mortality.
"A recent Cochrane Review also found that supplementation reduced the risk of pneumonia by 13% in children under 5."
The authors note that high zinc intakes can increase copper losses and contribute to deficiency therefore they recommend supplementation should be combined with a copper component.
Another recent report by a researcher from LymeCenter, in the Netherlands, evaluated evidence showing zinc status related to antiviral immunity and its possible role in COVID–19 and concluded that zinc is a critical factor for antiviral immunity.
The report states: "There is ample evidence suggesting that zinc depletion, also prevalent in high–income nations, compromises immune functions. Notably, major risk groups for COVID–19, the elderly, men more than women, obese individuals and patients with diabetes are all at risk of zinc deficiency.
"Moreover, various widely used antihypertensive drugs and statin therapy have been reported to negatively influence zinc status. As zinc depletion impairs antiviral immunity, it is hypothesised to increase susceptibility for COVID–19.
"Therefore, dietary preventive measures and prompt implementation of zinc supplementation for risk groups should be considered. Large–scale studies are urgently needed to investigate the role of micronutrients and antiviral immunity, in particular drug–micronutrient immunity interaction."
Source: BMJ Nutrition, Prevention and Health
McAuliffe S, Ray S, Fallon E, et al
"Dietary micronutrients in the wake of COVID-19: an appraisal of evidence with a focus on high-risk groups and preventative healthcare"