COVID-19: How do I boost my immune system?

Tuesday, April 21, 2020. Author FitnessGenes

COVID-19: How do I boost my immune system?

“How do I boost my immune system?”

Many of us are asking this question, especially now, during the ongoing COVID-19 pandemic.

Unfortunately, it is a question fraught with issues.

Firstly, there are issues with the concept of “boosting” the immune system. Our immune system is a complex network of tissues, cells and proteins that protects us against pathogens: disease-causing microorganisms such as bacteria, viruses and fungi.

In this respect, the idea of “boosting” the immune system has little scientific meaning. It doesn’t correspond to increasing numbers of immune cells or making an immune response more potent (both of which, incidentally, can sometimes be damaging to our health).

Perhaps a better question to ask is “How can I maintain a healthy immune system and/or reduce my susceptibility to infections and illnesses?”

While this question is more scientifically meaningful, we still need to tread carefully.

For one, measures that have been shown to maintain the healthy function of immune cells aren’t always linked to a reduced risk of infections on a larger public health scale. As we’ll find out in this article, Vitamin C may fall into this category.

More importantly, where COVID-19 is concerned, we simply do not yet know enough about the impact (if any) of maintaining a healthy immune system and risk of developing this new disease. Furthermore, we can’t generalise from findings based on other infections.

For example, as discussed below, there is some good evidence to suggest that Vitamin D supplementation can help cut the risk of acute respiratory tract infections, including those caused by common cold and influenza viruses. It doesn’t follow from this, however, that Vitamin D will protect us against infection from the SARS-CoV-2 virus (responsible for COVID-19).

 

A healthy lifestyle for a healthy immune system

With all the above caveats in place, there are various lifestyle measures that can help us maintain a healthy immune system. It’s mostly stuff we already know and nothing on the list will be particularly surprising!

While we do not currently know how these influence your risk of developing COVID-19, there's enough evidence to suggest they'll support your overall physical and mental health:

  • Eat a healthy, balanced diet.

  • Consider Vitamin D supplementation.

  • Exercise regularly, but not excessively.

  • Get enough sleep.

  • Minimise stress.

  • Limit alcohol consumption.

  • Stop smoking. 

This article will take a critical look at some of the vast scientific literature supporting these measures.

Even if you adopt all of these lifestyle strategies, it’s important not get to a false sense of security. People with a healthy immune system are still very much susceptible to COVID-19.

As such, it remains essential to adhere to public health advice on social distancing, handwashing, face masks and regular disinfection.

What is the immune system?

Before examining various lifestyle measures, it’s worth taking a quick look at the different parts of our immune system.

Our immune system is the complex network of tissues, cells and proteins that helps protect us from infective agents or ‘pathogens’.

Rather than being a discrete set of organs, the immune system involves various kinds of cells distributed across different sites in the body. Immune cells can move between these sites in our bloodstream and lymphatic system.

Broadly speaking, we can divide the immune system up into two main strands:

  • the innate immune system
  • the acquired (or adaptive) immune system

Innate immune system

The innate immune system is our first line of defence against pathogens. It includes physical barriers, such as the skin and mucous membranes that line our respiratory and gastrointestinal tracts. These act to prevent pathogens from invading into tissues.

Inflammation is another part of the innate immune response, which involves dilation of blood vessels, release of inflammatory proteins, and the migration of various immune cells to help neutralise and clear pathogens.

White blood cells are also key components of the innate immune system. In particular, white blood cells known as phagocytes play an important role in engulfing, digesting and destroying pathogens and infected cells. This process is known as phagocytosis. There are various kinds of phagocytes in the immune system, including macrophages, monocytes and neutrophils.


Another important type of white blood cell of the innate immune system is the natural killer cell. These help to destroy cells infected with viruses.

The hallmark of the innate immune system is that it is non-specific. This means it protects against any agent that is identified as foreign or ‘non-self.’ It isn’t specific to a particular pathogen.

The other distinguishing feature of the innate immune system is that it’s quick, acting within minutes to hours.



Acquired (or adaptive) immune system

Unlike the innate immune system, the acquired immune system is specific to particular antigens: molecules that are unique to different pathogens and are found on their surface.

For example, viruses may have unique proteins on their surface that activate cells of the acquired immune system.

By recognising, mounting an immune response against, and then “remembering” specific antigens, the acquired immune system allows us to develop immunity to various pathogens throughout life. If we are then re-exposed to the pathogen (or, more accurately, its antigen), we can then more quickly and effectively clear it.

The two main cells of the acquired immune system are:

  • B-cells – which produce antibodies that bind to specific antigens and neutralise pathogens. This type of immunity is known as humoral immunity.
  • T-cells – that destroy infected cells or secrete chemicals called cytokines to recruit other immune cells and coordinate the immune response. This type of immunity is known as cell mediated immunity.

B and T cells can also specialise to form memory cells, allowing us to “remember” antigens and respond to them more effectively next time we encounter them.

In contrast to the immune system, our acquired immune system is much slower and takes days to mount a response.

Examining the evidence base

In the following sections, we will examine the evidence base behind lifestyle measures (e.g. taking vitamin supplements) and susceptibility to infections (particularly upper respiratory tract infections – which are the most common infections in an outpatient setting).

As there are hundreds of studies in the scientific literature, we will mainly focus on meta-analyses.

A meta-analysis is a type of statistical procedure that pools and standardizes the data from several studies. It aims to account for differences in sample size, study design and findings to calculate the overall effect of an intervention – e.g. vitamin supplements.

Meta-analyses are considered to be the top of the evidence-base hierarchy for an intervention.

In particular, Cochrane reviews, which use rigorous methodology, are largely considered the gold-standard of evidence by clinicians. We’ll try to cite these where possible.

 

Tip 1: Eat a healthy, balanced diet

In order to function effectively, our immune system requires a sufficient dietary energy intake, as well as adequate amounts of macronutrients (protein, carbs, and fat) and micronutrients (vitamins and minerals).

We know that immune function is less effective in people who are undernourished and in those with nutrient deficiencies. Consequently, these groups are more susceptible to infections.

The vast majority of us, however, can easily avoid such deficiencies by eating a healthy, balanced diet. In particular, a diet that has a variety of fruit and vegetables ensures we will receive the Recommended Dietary Allowance (RDA) for several micronutrients.  

But, are there any particular micronutrients we should focus on? What about supplements? Are there any I should be taking to help my immune system and reduce my risk of infections?

Should I take Vitamin A supplements?

Vitamin A plays a number of important roles in both the innate and acquired immune systems.

It helps maintain the integrity of physical barriers such as the skin and linings of the respiratory and gastrointestinal tracts. Vitamin A is also required for the effective function of innate immune cells, including natural killer cells (that destroy virally-infected cells) and neutrophils (which ingest and destroy pathogens).

In the acquired immune system, Vitamin A is involved in the development and function of B and T cells, which target specific antigens.

Despite these roles in the immune system, the clinical evidence base that Vitamin A supplements lower your risk of infections is scant.

 

What do studies say?

The majority of clinical studies into Vitamin A and immune function have focussed on children rather than adults. Deficiency of Vitamin A is linked to poorer immune function, increased mortality and a higher risk of diarrhoea and measles in children.

It’s important to note, however, that Vitamin A deficiency is rare in the developed world, and a regular intake of Vitamin-A rich foods (e.g. beef liver, oily fish, milk, spinach, carrots) is usually enough to prevent deficiency.

Nevertheless, individuals with bowel disorders that impair Vitamin A absorption (e.g. celiac disease) and those following strict vegan diets are at an increased risk of Vitamin A deficiency.

Certain gene variants may also reduce the conversion of α and β carotene (found in fruit and vegetables) into active forms of Vitamin A that can be used by the body. You can find out whether you carry these variants in your Vitamin A requirement trait.  

Beyond preventing Vitamin A deficiency, however, there is currently no strong evidence that Vitamin A supplementation helps to reduce risk of infections in healthy individuals.

On this note, a meta-analysis pooling data from 33,179 children (under 7 years old) found that Vitamin A had no effect on the risk or severity of symptoms of acute lower respiratory tract infections (e.g. pneumonia and bronchiolitis).   


Should I take Vitamin C supplements?

It is widely believed by the general public that Vitamin C “boosts the immune system”. The scientific evidence to back this belief, however, is less clear cut.

It is certainly true that Vitamin C is important for both innate and acquired immune function. Vitamin C helps to stimulate the production, development and movement of various white blood cells, including innate immune cells such as neutrophils and phagocytes, as well as B and T-lymphocytes that are part of the acquired immune response.

As a potent antioxidant, Vitamin C also protects white blood cells from damage caused reactive oxygen species (ROS) that are generated during an immune response.

Alas, despite these demonstrated roles of Vitamin C on a cellular level, the evidence that consuming more Vitamin C can reduce susceptibility to infection and illness is mixed.  


What do studies say?


Vitamin C and risk of common cold

A 2013 Cochrane Review investigated the effect of Vitamin C on the prevention and treatment of the common cold.

Collating the data of 11,306 subjects across 29 placebo-controlled trials, it found that taking Vitamin C doses greater than or equal to 0.2 g per day had no effect on the risk of developing common cold in healthy individuals.

Interestingly, however, in an analysis of 598 heavily exercising marathon runners, skiers and soldiers on subarctic training, the same study found that Vitamin C reduced the risk of developing a cold by 52%.

Heavy exercise is known to cause oxidative stress and resultant damage to the lining of the respiratory tract. This may increase susceptibility to upper respiratory tract infections (e.g. common cold). It’s possible that Vitamin C protects against this through its antioxidant activity.

Therefore, if you take part in intense physical exercise (e.g. running a marathon), then it may be worth considering increasing your Vitamin C intake to reduce your chances of catching a cold. (Again, please note, we do not currently have any understanding of the relationship between Vitamin C and risk of COVID-19).

The review also investigated whether taking Vitamin C reduced the duration of common cold symptoms. The researchers found that regular Vitamin C supplementation shortened the length of common colds in adults by 8%. This reduction in common cold symptoms was more pronounced in trials using larger doses (6-8 g per day) compared to lower doses.

In light of these findings, the authors concluded that “given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them.

 

Vitamin C and risk of pneumonia

Another Cochrane Review studied whether Vitamin C helped to prevent pneumonia – a lower respiratory tract infection causing inflammation of the small airways and air sacs (alveoli) of the lung.

The review revealed only three trials, with each one finding a statistically significant (80% or greater) reduction in the incidence of pneumonia for subjects taking Vitamin C.

Despite this positive finding, the subjects in these trials were either soldiers or schoolchildren from low income backgrounds, who may have had marginal Vitamin C deficiency. This makes it impossible to tell whether healthy adults with a balanced diet and normal Vitamin C levels would benefit from taking more Vitamin C to cut their risk of pneumonia.

On a related note, it is plausible that people with lower blood and tissues levels of Vitamin C may stand to benefit more from supplementation, although more robust research is needed. You can find out whether you carry rare and/or common gene variants linked to lower plasma Vitamin C levels in your Vitamin C Level (SLC2A1) trait.

Nevertheless, as the authors of the Cochrane Review conclude, “the current evidence is too weak to advocate prophylactic use of vitamin C to prevent pneumonia in the general population.”

Tip 2: Consider taking Vitamin D supplements

Vitamin D, sometimes known as ‘the sunshine vitamin’, is arguably the micronutrient with the greatest evidence base to support supplementation.

It plays a variety of roles in the immune system and acts primarily by binding to the Vitamin D receptor found on the surface of various immune cells.

For example, once bound to this receptor, Vitamin D stimulates white blood cells called macrophages to engulf pathogens (i.e. phagocytosis). It also causes macrophages to secrete specialized antimicrobial proteins that neutralise pathogens, especially bacteria.

When it comes to the acquired immune response, Vitamin D actually suppresses the production of antibodies by B-lymphocytes. It also inhibits the proliferation of T-lymphocytes.

This suppressive effect may actually be beneficial, as it may help to prevent autoimmunity – whereby the immune system attacks our own healthy cells.

 

What do studies say?

A 2017 meta-analysis published in the British Medical Journal investigated the effect of Vitamin D supplementation on acute respiratory tract infections. This term includes upper respiratory tract infections (e.g. the common cold), as well as lower respiratory tract infections (e.g. pneumonia).

Collating the data of 10,933 subjects across 25 randomised controlled trials, the researchers found that Vitamin D supplementation was associated with a 12% reduced risk of acute respiratory tract infections.

This beneficial effect was stronger in subjects taking daily or weekly supplements, rather than those receiving large, one-off bolus doses (greater than 30,000 IU of Vitamin D).

Furthermore, the protective effect of Vitamin D was stronger in individuals with lower baseline Vitamin D levels (or, more specifically, blood 25-hydroxy-Vitamin D levels).

On this note, people with a baseline Vitamin D level less than 25 nmol/L had a much greater (70%) reduction in risk of respiratory tract infection compared to those with higher (greater than or equal to 25nmol/L) Vitamin D levels (15% cut in risk of infection).

To put those figures in context, healthy blood Vitamin D levels are generally considered to be between 50nmol/L and 125nmol/L. People with Vitamin D levels under 30nmol/L are classified as severely deficient.

 

Many of us are deficient in Vitamin D

Interestingly, in contrast to other micronutrients, a substantial proportion of Westernised populations are deficient in Vitamin D. Using figures from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2010, researchers found that 28.9% of US adults had Vitamin D deficiency (<50nmol/L).

Older adults and people with darker skin are at higher risk of Vitamin D deficiency. This is because their skin is less effective at making Vitamin D from sunlight. Similarly, people with limited sun exposure are at greater risk of deficiency. This includes those of us living in countries further from the equator, who typically experience limited periods of sunlight during autumn and winter months (e.g. the UK).

Certain gene variants can also put us at higher risk of low Vitamin D levels. You can check whether you carry these variants in your Risk of Low Vitamin D levels trait.  

Given the demonstrated impact of Vitamin D supplements on risk of respiratory tract infections, coupled with the fact that many of us are at risk of Vitamin D deficiency, it’s certainly worth considering taking a Vitamin D supplement.

Should I take zinc supplements?

Zinc is an essential mineral that plays a number of roles in both the innate and acquired immune systems.

It helps maintain the integrity of skin and other physical barriers that prevent pathogens from invading into tissues. Zinc also regulates the release of signalling molecules, called cytokines, which are secreted during an inflammatory response.

In the acquired immune system, zinc plays a key role in the development and activation of T cells.

We know from studies of children in low and middle-income countries that zinc deficiency is associated with an increased risk of bacterial, viral and fungal infections, particularly those causing diarrhoea and pneumonia.

Currently, however, research into whether zinc supplementation can cut risk of infections in healthy adults is lacking.

 

What do studies say?

A lot of studies into zinc have focussed on children, particularly children from low and middle income countries, who are more likely to have zinc deficiency.

On this note, a Cochrane Review looking at children aged between 2 and 59 months found that zinc supplementation is associated with a reduced risk of pneumonia.

The evidence base for zinc supplementation in healthy adults is less established. A 2013 Cochrane Review did investigate the role of zinc on the incidence, severity and duration of common cold symptoms.

Collating the data from 1781 subjects, researchers found that zinc (in the form of syrup or lozenges) was effective at reducing the duration, but not severity, of cold symptoms.

Note that treating a cold infection and preventing a cold are different things. We are more interested in the latter as far as reducing our risk of illness is concerned.

Nevertheless, the same Cochrane Review found that the incidence rate of common cold was 36% in subjects supplementing with zinc compared to those not taking zinc.

We shouldn’t generalise too much from this however, as this figure was based on only two studies, one of which was considered to be of poor quality.

All in all, then, it seems that much more robust research is needed to find out whether healthy adults should be taking zinc supplements to cut their risk of infections.

You can find out more about how your genes affect your zinc levels in your Zinc requirement trait.

Tip 3: Exercise regularly, but not excessively

We all know that regular exercise is good for us. So, exercise must also support our immune system and cut our risk of infections, right?

The answer to this question actually depends on the intensity and duration of exercise.

Studies suggest that exercise bouts under 60 minutes long and of moderate-to-vigorous intensity (60% of maximum oxygen consumption) can have beneficial effects on our immune system.

An acute bout of exercise under 60 minutes is shown to increase the exchange of various white blood cells between lymphoid tissues and the bloodstream. This is thought to improve something called immunosurveillance - the ability of our immune system to sniff out, recognise and respond to foreign pathogens.

By contrast, very intense or prolonged endurance can actually impair the function of immune cells in the several hours to days following exercise. This is known as exercise-induced immune dysfunction.

For example, the graph below shows the contrasting effects of running a marathon (intense and prolonged exercise) versus 30-45 minutes of walking (moderate exercise) on various immune markers.

Exercise and risk of infections

Several studies have investigated the effects of exercise versus no exercise on the risk of respiratory tract infections (RTIs).

A recent (April 2020) Cochrane Review, which pooled the data from 1377 adults across 14 clinical trials, found that exercise decreased the severity and duration of respiratory tract infection symptoms.

Despite this finding, the study found no significant difference in the number of RTI episodes between exercise and control (no exercise) groups.

Nevertheless, other longitudinal studies, which have followed people over time and looked at differences in activity levels, have found that more physically active individuals have a 18-29% decreased risk of illness compared to those with low physical activity.

Once again, however, the risk of infection is likely to depend on the intensity and duration of exercise.

Although a subject of debate, several studies suggest that heavily training elite athletes and soldiers have a higher rate of upper respiratory tract infections (such as cold, flu, sore throat) compared to the general population.  

Based on these findings, the relationship between exercise and upper respiratory tract infections (URTIs) is likely to follow a J-shaped curve.

This means that while doing no exercise whatsoever is harmful to physical health and infection risk, so is exercising excessively. There’s probably a sweet spot in the middle linked to healthier immune function and reduced respiratory tract infection risk.

The current consensus seems to be that regular bouts of exercise between 45-60 mins are beneficial for immune function.

Tip 4: Get enough sleep

Sleep has a variety of effects on both our innate and acquired immune systems.

Nocturnal sleep (i.e. sleeping at night-time) is shown to support the function of natural killer cells (part of the innate immune response), as well as T cells (part of the acquired immune system).

Furthermore, sleep regulates the activity of the hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system, which are responsible for our acute stress response. Both these systems have a strong influence on immune function.

In experiments where subjects have undergone partial and total sleep deprivation, immune system function is shown to be altered. For example, sleep loss changes the production of inflammatory cytokines and reduces the number of natural killer cells.

 

What do studies show?

An analysis of the Nurses’ Health Study II tracked the sleep patterns and health outcomes of 56,953 healthy, female adults between 2001 and 2005.

It found that those with short or long sleep durations had an increased risk of developing pneumonia compared to people who slept 8 hours per night.

Participants sleeping less than 5 hours a night had a 1.39 times higher risk of pneumonia compared to those sleeping 8 hours per night. Those sleeping more than 9 hours per night had a 1.38 times increased risk.

Another smaller study (n=164) involved administering nasal drops containing rhinovirus (known to cause the common cold) to healthy volunteers. They were then followed up to see whether they developed the cold over the next 5 days.

The study showed that those sleeping less than 6 hours per night were more likely to develop symptoms of a cold compared to those sleeping 7 or more hours per night.  

Given these findings, if you want to maintain healthy immune function, it’s crucial to get enough good quality sleep.

If you’re looking for advice on getting a good night’s sleep, the actions in your Sleep/wake cycle, Sleep and weight gain risk, and Seasonal Affective Disorder traits all contain personalised tips based on different gene variants you carry.

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