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 The virus itself has been named SARS-CoV-2 as it has been determined as the same species as SARS but a different strain of the species.

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. The ramification of SARS-CoV-2 is atypical viral pneumonia, with the main treatment strategy of supportive care, which may include oxygen or artificial ventilation.12 Antibiotics are of no use to treat viral pneumonia. The fatality rates in China (and now Italy) follow a distinct pattern, with the elderly having the highest death and case fatality rate (figure 1 and table 1).13 In particular, older patients (>65 years) with underlying health conditions, including acute respiratory distress syndrome, are at increased risk of dying.12

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Figure 1

Death rates in China, by age. Data extrapolated from Porcheddu et al.13

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. In his article ‘Feeding the Immune System’, he explains that the immune system functions by acting as an exclusion barrier, identifying and eliminating pathogens and involving complex interplay between many different cell types and chemical mediators.5

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.

Nutrition focus

As discussed, we are in the information era, and with this there are many online nutritional myths about how to bolster the immune system.6 However, a number of scientific reviews and research publications have been published focusing on the role of diet and specific nutrients in the immune system, some of which have focused on respiratory viral infections. Here we discuss some of the main findings.

One recent review25 identified that an array of micronutrients are required to meet the complex needs of the immune system, including vitamins A, D, C, E, B₆, B₁₂, folate, copper, iron, zinc and selenium, with many of these having potential synergistic relationships. Of the evidence, however, it was concluded that the largest body of evidence related to immune function existed for vitamin C, D and zinc.25 Hereon we subsequently focus on these nutrients with specific reference to the evidence on respiratory health.

The need for more research

Given the rapid transmission of COVID-19, scientists are working against the clock to find potential vaccines, antiviral medications or other possible solutions. One intervention could potentially be the reinforcement of the immune function, a strategy that could be particularly worthwhile among vulnerable groups such as those aged >65, with underlying health conditions, such as asthma, chronic obstructive pulmonary disease, diabetes and heart disease, or who are immunosuppressed. Unfortunately, high-quality, rigorous trials are currently lacking. Most of what we know are based on observational evidence or older studies conducted on military populations.

Hopefully now more funds will be invested into nutritional immunology and its applications among ageing populations and those with viral respiratory conditions. This could be a viable approach given the relatively low cost of vitamin D, C and zinc supplements. What remains to be confirmed are the dosages and durations that these would need to be taken to be most beneficial and whether different combinations of micronutrients would be most effective in helping to fight against infection.

As previously mentioned, vitamins A, E, B₆, B₁₂, folate, copper, iron and selenium are other examples of nutrients that possess important role(s) in helping to meet the complex needs of the immune system.25 These may work individually or in synergy. Furthermore, it is highly likely that other dietary components could also play a role in the modulation of immunity, but are yet to be identified.

Given the recent shifts towards food shortages layered on top of the already pressing concerns about food insecurity in older adults, this could only further hamper the nutritional density and micronutrient profiles of diets. Further interventions and public health strategies should therefore consider the value of distributing both food and nutrition supplementation packages to the vulnerable.

Summary and perspective

Unfortunately, the transmission and speed at which COVID-19 is spreading globally appear to be surpassing the speed at which nutritional immunology studies can give firm answers. An insight into the evidence that is currently available indicates that from an immunological and respiratory stance, ageing populations are undoubtedly more ‘at risk’ from the harmful ramifications of such infections. Subsequently, a number of nutritional strategies could help them, taking on board what we know so far:

• Public health strategies involving immunonutrition could be an alternative way to promote prehabilitation and reduce burdens on healthcare systems.

• The general public and indeed the ageing population should be encouraged to follow guidance from Public Health England44 and continue taking supplements containing 10 μg of vitamin D daily, given the fact that low vitamin D status appears to correlate with reduced immune function. Family and friends should help communicate this information to older generations given that they may have limited awareness of these guidelines.

• Foods that are naturally abundant in vitamin C such as broccoli (60 mg/100 g), blackcurrants (130 mg/100 g), fortified breakfast cereals (up to 134 mg/100 g) and oranges (37–52 mg/100 g)45 should be made accessible to older individuals who are most in need of their nutritional benefits.

• In the UK 5.5% of men and 4% of women 65 years and over (around 1 in 20) presently have zinc intakes lower than the lower reference nutrient intake (the level below which deficiency could occur).46 The consumption of foods naturally abundant in zinc such as canned crab (5.7 mg/100 g), canned shrimps (3.7 mg/100 g), canned adzuki beans (≈2.3 mg/100 g) and boiled eggs (1.3 mg/100 g) should be encouraged as a supplementation strategy to reinforce immunity.

• Among those with established respiratory conditions or pneumonia, specific nutrients such as vitamin C, D or zinc could be considered as potential adjuvants to conventional treatment pathways.

• Tolerable upper intake levels (ULs) are intake levels which should not be surpassed as toxicity problems could appear.47 For vitamin D a UL of 50 µg/day is advised and for zinc a UL of 25 mg/day is recommended.47 There is insufficient evidence to establish UL for vitamin C, but available human data suggest that supplemental daily doses of up to about 1 g, in addition to normal dietary intake, are not associated with adverse gastrointestinal effects.47 Not having an adverse effect, however, is not necessarily indicative of a benefit either, and ongoing trials are warranted.

• Every individual patient should be carefully assessed when providing nutrient intakes higher than the reference nutrient intake, and dosages should preferably be clinically validated for critically ill patients.

• Now that a pandemic has arisen with SARS-CoV-2, and given the easy access, low cost and limited side effects of the discussed nutrients, now could be an appropriate time to trial and test their efficacy in relation to prevention, severity and recovery of such infections.

• Ongoing research is urgently needed within the field of immunonutrition and, in particular, how this could benefit vulnerable, at risk groups.