Introduction
Coronaviruses are important pathogens to animals and humans and have been around for many years. Severe acute respiratory syndrome was first detected in Guangdong in southern China in 2002 and the Middle East respiratory syndrome followed and first emerged in Saudi Arabia in 2012.1 Both result in severe respiratory infections, which can be fatal.1 In late December 2019 a further coronavirus emerged, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the potentially fatal COVID-19 disease.2
Most public health strategies being employed are currently reactive. However, immunonutrition could have an important preventative role—a form of ‘prehabilitation’ helping the body to cope with potentially lethal viruses such as coronavirus. Elsewhere, prehabilitation has been defined as ‘interventions that can help to improve patient’s health in advanced of being exposed to a physiological stressor so they are then better able to cope with that stress’.3 It is known that viral clearance and infection recovery require activation of the host’s immune response, and nutrition could be a means of achieving this.4 Suboptimal immune competence commonly occurs in later life, with undernutrition, protein-energy malnutrition and micronutrient deficiencies being age-related lifestyle factors that can further hamper this.5
Severe acute respiratory syndrome coronavirus 2
In late December 2019 a novel coronavirus emerged in Wuhan, Hubei Province, China and is the most recent emerging pathogen of a potentially fatal disease that has rapidly become a global public health concern.2 In February 2020, the World Health Organisation (WHO) named the disease COVID-19.2 By 11 March 2020 the WHO went on to further recognise COVID-19 as a global pandemic.7
Coronaviruses are a family of viruses known to infect mammals and birds, belonging to the family Coronaviridae.8 Before the emergence of COVID-19, there were six different coronaviruses known to infect humans, four of which cause a mild common cold-type illness.9 The remaining two coronaviruses emerged in 2002 and 2012 and result in a more severe disease in humans. These were named severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) and are highly pathogenic viruses.9 Both SARS and MERS are believed to have originated in bats, suggesting animal to human transmission.9
SARS-CoV-2 has emerged as the third known coronavirus that causes fatal respiratory diseases in humans. The causative pathogen was isolated by Chinese researchers in January 2020 and discovered to be a large enveloped virus with a positive sense, single-stranded RNA genome of about 26–33 kb.1 The SARS-CoV-2 shares 96% similarity to bat coronavirus at the whole genome level, which suggests, like SARS and MERS, bats were the original host, with an intermediate host prior to infecting humans.9 It will be vital to track the path of the virus in order to prevent future exposure and outbreaks. In terms of the development of vaccines and antibody-based therapies, it will be important to understand the mutation rate of SARS-CoV-2, which appears to be moderate to high and similar to the other coronaviruses.10
Unfortunately, no vaccines against coronaviruses have ever been developed, including for SARS or MERS, with MERS still remaining largely uncontrolled.11 Similarly, there is no single specific antiviral therapy.
Immunity focus
The human immune system is comprised of four central components—T cells, B cells, the complement system and phagocytes which are vital in defending the organism against foreign intruders.14 The immune system is the body’s primary defence barrier against infections, and thus any weaknesses could be potentially detrimental to the host.15–17
It has been recognised that a ‘well-fed’ immune system is one way of helping to provide defence against pathogenic organisms.5 It has been elegantly stated that an ideal immune system should be ‘constantly alert and monitoring for signs of danger or invasion’.4 Professor Philip Calder is one of the leading experts in nutritional immunology and has published widely on this topic.
Unfortunately a decline in immune function is usually inevitable with ageing, a process referred to scientifically as ‘immunosenescence’, which typically involves the deterioration of both innate and acquired immune systems.18 19 A number of potential mechanisms have been proposed, including (1) declining T cell function attributed to thymic involution and subsequent reduced output of naïve T cells20; (2) ageing-associated inflammation, often referred to as ‘inflammaging’, which paradoxically can reduce immunity and contribute to pathogenic age-related diseases21; and (3) poor micronutrient status – a bidirectional relationship between infection/immunity and nutrition whereby changes in one of these components can impact the other.22 It is also becoming apparent that ageing can modulate immune function and cellular composition in ways that are sex-specific, possibly due to differences in how menopause and andropause unfold.23
With regard to respiratory conditions, the combined effects of compromised immune function, frailty and length of exposure to pathogens mean that ageing populations are naturally predisposed to pulmonary disease.24 Nevertheless, there is hope—innate and acquired immune function may be supported by human nutrition, particularly in instances where this is suboptimal, that is, in clinical settings and the aged, potentially helping to lower the risk of infections and their severity and promote recovery from these.
Vitamin C
In terms of potential mechanisms, it is well recognised that infections increase oxidative stress.26 Infections typically activate phagocytes which release reactive oxygen species, which are oxidising agents.26 Vitamin C is a renowned antioxidant which can counteract these effects.26 In one study a respiratory syncytial virus reduced the expression of antioxidant enzymes and subsequently increased oxidative damage.33
Vitamin D
A number of studies have investigated the inter-relationships between vitamin D and its effects on respiratory viruses and conditions such as community-acquired pneumonia.34–37
It is well appreciated that vitamin D is a powerful immunoregulator, with vitamin D receptors being expressed by the majority of immune cells (B and T lymphocytes, macrophages and monocytes).38 It has also been proposed that immune cells themselves can convert 25(OH)D3 into 1,25(OH)2D3, its active form.38
Zdrenghea et al34 reported in their review that respiratory epithelial cells, macrophages and monocytes express vitamin D receptor, and concluded that vitamin D could act as a potential adjuvant in protecting and treating patients with respiratory viral infections who typically have lower vitamin D status. Work by Greiller and Martineau35 also reported that vitamin D deficiency is associated with a higher risk of viral acute respiratory infection and found that vitamin D metabolites modulated the expression and secretion of type 1 interferon, chemokines CXCL8 and CXCL10, and proinflammatory cytokines, including tumour necrosis factor and interleukin-6.
Another study,36 using human bronchial epithelial cells infected with respiratory syncytial and rhinoviruses (with or without exogenous D), showed that both viral strains reduced the number of vitamin D receptors and 24-hydroxylase. However, despite this, exogenous vitamin D was shown to increase antiviral defences and increase rhinovirus-induced interferon-stimulated genes and cathelicidin, implying a protective response.36 Other work37 focusing on pneumonia found a negative association between 1,25(OH)2D3 and pneumonia severity.
A systematic review and meta-analysis39 has collated evidence from 25 separate randomised controlled trials (n=11 321 participants) studying the effects of vitamin D supplementation on acute respiratory infections among those aged 0–95 years. Protective effects were seen among all participants, but particularly among those with baseline 25-hydroxyvitamin D levels <25 nmol/L, indicative of deficiency.39 Overall, the authors concluded that vitamin D appeared to be a safe strategy to protect against acute respiratory tract infections.39
Zinc
Zinc is regarded as a ‘gatekeeper’ of immune function: it is essential for the functioning of the immune system.40 Zinc ions play a role in the regulation of intracellular signalling pathways in adaptive and innate immune cells.40 Zinc is also involved in inflammation, elevating inflammatory responses and inducing cell-mediated immunity, and is a key component of pathogen-eliminating transduction pathways that contribute to neutrophil extracellular traps (networks which bind pathogens) formation.41
No meta-analysis or Cochrane reviews currently appear to have been undertaken in this field. Among paediatric populations a review of several studies42 concluded that zinc supplementation for more than 3 months could be effective in preventing pneumonia in children younger than 5 years of age, although the evidence was not robust enough to advocate prophylactic properties if given for shorter periods of time. Among the elderly it is recognised that inadequate zinc status impairs immune function, reduces pathogenic resistance, and is linked to an increased incidence and duration of pneumonia, along with overall mortality.43 Rigorous trials, however, are yet to determine the efficacy of zinc supplementation.
Referência:
BMJ Nutr Prev Health. 2020 Apr 16;3(1):100-105.