In this episode, Wendy McLean, Educator at vital.ly, discusses diet, lifestyle and environmental factors that affect our immune resilience and the implications for individuals with COVID-19.
Specifically, she discusses key immune nutrients, the gut and lung microbiome's role in immunity, and the benefits of physical exercise, stress reduction techniques, and prosocial beviour for building immune resilience.
00:01: Today, I'm going to be looking at the importance of immune resilience, specifically in these current times of COVID-19. I'm going to look at the factors affecting our resilience and how we can support it through diet and lifestyle.
So what is immune resilience? Immune resilience is the ability of the body to adapt and respond to adverse conditions such as bacterial pathogens, viral infections, and abnormal or cancerous cells, and return the body to a state of homeostasis, that is, a state of wellbeing. A resilient immune system is potent specific, controlled, and adaptive. That is, it can mount an appropriate immune response to eliminate a harmful agent without harming self or commensal bacteria, and it can adapt to these ever-changing threats. And considering the COVID-19 pandemic, many of the health issues that we're seeing arise from impaired or loss of resilience, which is impacted by lifestyle choices, nutrition, and our environment.
01:07: So just to review the threat, the coronavirus disease 19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It is a novel RNA virus and it infects host cells through bonding with the angiotensin converting enzyme 2 receptor (ACE-2 receptor), which is mainly expressed in a variety of endothelial cells, lining the lungs, intestines, kidneys, gastrointestinal tract, and blood vessels. Once inside the cell, the virus multiplies by overtaking the host cell machinery, and it stimulates innate and adaptive immune responses. We know that about 40 to 45% of infected individuals are asymptomatic. And of those that are symptomatic, about 80% of people will have mild to moderate symptoms. Unfortunately, 20% of symptomatic patients will have severe or critical illness and will suffer complications and life-threatening illness. And these complications include, inflammation, the cytokine storm, oxidative stress, hypoperfusion, endothelial dysfunction and microemboli. Much of the critical illness associated with the virus is believed to be the result of this hyper inflammatory process, which is called the cytokine storm.
02:32: And this cytokine storm is characterised by sustained activation of infiltrating macrophages and elevated cytokines and chemokines such as interleukin 6. And it's associated with a number of factors. There may be an underlying inflammatory pathology, an impaired interferon one response early on in the infection, oxidated stress and inflammasome and nuclear factor kappa beta activation. It is also observed that critically ill patients produce lower levels of T-cells because the constant immune stimulation exhausts the immune system and weakens the T cells. The controlled and sustained systemic inflammatory response may lead to pathological consequences, including extensive pulmonary oedema, acute respiratory distress syndrome, sepsis, multiorgan failure and disseminated intravascular coagulation and unfortunately the acute respiratory distress syndrome is the main cause of death in about 70% of COVID-19 fatalities.
03:42: It's not just the immediate viral infection we need to worry about, but also the long-term health sequelae. Typically the majority of people recover from COVID-19 in about two to six weeks. However, emerging data suggests that at least 30% of infected individuals suffer long-term symptoms. And it's not just the critically ill that are experiencing this, but also those who may have only had a mild or moderate case of COVID-19. There was a study published recently from Wuhan, China, looking at long-term effects in nearly 2000 individuals. 76% of patients reported at least one symptom six months after symptom onset and symptoms were more frequent in women than men. Most common symptoms were fatigue, muscle weakness and sleep difficulties. And 23% of patients reported anxiety or depression. Co-morbidities were common with the most common co-morbidity being hypertension. And unfortunately, we're seeing a whole range of these long-term symptoms ranging from brain fog to chronic fatigue, hair loss, cardiovascular issues, and impaired kidney function.
05:00: These symptoms are debilitating, and those who experience them have been dubbed the long haulers. We don't know how long some of these symptoms will last, but we can look to previous coronaviruses for an idea. There were studies published, looking at the SARS pandemic in 2003, and it was found that even 24 months after infection survivors still had impaired exercise tolerance and nearly three and a half years after being diagnosed, 40% of people still had chronic fatigue symptoms. And we can look even further back at the 1918 influenza panic pandemic. The virus had long-term impacts on cohorts exposed in utero, which experienced earlier adult mortality, more diabetes, ischemic, heart disease, and depression after the age of 50 .
And the, consistent observation has been the difference in severity of COVID-19 at different ages. What we're seeing is that if children are infected, they get a much milder case or they're asymptomatic, compared to adults. And this was observed in these previous coronoavirses, in SARS in 2003, and the Middle East Respiratory Syndrome in 2012. We don't fully understand the reasons. However, there are a number of factors that could explain the difference in severity between children and adults. In adults, we have age-related endothelial damage, changes in clotting function, there's immunosenescence and inflammation. They may have a co-morbidity or several co-morbidities. They may have lower levels of vitamin D. And factors that might protect children, include the differences in innate and adaptive immunity. Children have a stronger innate immune response, which is the first line of defense against the virus. And they have higher numbers of natural killer cells. They also have a higher frequency of infections, so they have this active immune system. They may have differences in microbiota compared to adults, higher levels of melatonin. And it's also proposed that there may be protective off target effects of live vaccines, such as the measles vaccine. These vaccines can promote an immune response that is nonspecific and systemic.
07:39: Resilience can be determined by our immune age. And our immune age is a new concept, which has been found to be a predictor of all-cause mortality. And it's related to these concepts of immunosenescence and inflammation, as well as our genetics. For example, a 40 year old could have the immune function of a 60 year old, and this makes them more susceptible to worse COVID-19 outcomes. Factors affecting our immune age, include our diet and nutrition or stress, lack of sleep, environmental factors, a lack of physical activity, genetics, lifestyle, and social isolation. So just looking at these two concepts, immunosenescence and inflammation. Immunosenescence is the aging associated decline in immune function. And concomitant with this is this low grade systemic inflammation, which is commonly termed inflammaging and is related to chronic diseases such as diabetes, cardiovascular disease and cancer.
Hallmarks of immunosenescence include changes in the adaptive immune system, so most prominently in the T-cell compartment, which is responsible for protecting against pathogens inside cells or cells that have gone awry. We also get changes in our antibody response and we get an increase in memory B cells. Our innate immune system is also affected. For example, our natural killer cell activity is impaired, as is our macrophage activity, and dendritic cells have an impaired ability to induce T-cell proliferation and also interferon gamma response. So this results in impaired antiviral responses.
We know that nutrition and lifestyle are critical for supporting immune resilience and they have a number of positive effects, not only modulating the immune response, but they decrease inflammation, oxidative stress, support a healthy gut microbiome, prevents endothelial dysfunction, increases telomere length, delays immunosenescence and reverses chronic disease. So ideally we would support immune resilience through our diet and our lifestyle.
10:01: When we think about nutrition, we want a diet that contains food and nutrients that enhance our immune and metabolic resilience. And it's not a one size fits all approach. When it comes to diet, we need to take a personalised approach and ideally our diet would supply adequate levels of the specific nutrients that are required for immune function. However, due to numerous factors, such as changing agricultural and dietary patterns, this is not always the case. And it has been estimated that at least 44% of the world population is suffering from malnutrition, either due to under-nutrition or over-nutrition, with both conditions, a risk factor for disease and disease severity. So nutritional supplementation may be required.
10:54: Some of our key immune nutrients, are vitamin C vitamin D and zinc. Zinc modulates the immune system, and it has anti-inflammatory and antiviral activities as well. A systematic review of randomised controlled trials has shown that zinc lozenges can reduce the duration of the common cold. Zinc and zinc ionophores have also been found to inhibit the SARS-CoV replication in vitro, and a zinc deficiency correlated with worse clinical presentation, longer time to reach stability and higher mortality in COVID-19 patients. And it's been proposed that the loss of taste and smell associated with COVID-19 may also be due to zinc deficiency.
Vitamin C is a powerful antioxidant, and it reduces the risk of free radical damage and cell damage. It has many different roles in the immune system. For example, it enhances natural killer cell maturation and activity, and increases levels of antibodies. A low vitamin C status increases susceptibility to infections such as pneumonia. And what we are seeing is that in individuals with acute respiratory distress syndrome and sepsis in COVID-19, they are deficient in vitamin C and intravenous vitamin C is actually being used in some of these cases.
Vitamin D enhances innate immunity by up-regulating anti-microbial peptides in response to infection. It modulates the immune system, as well with effects on T and B lymphocytes and dendritic cells. It's also anti-inflammatory. It has been shown to protect against acute respiratory tract infections in human clinical trials, particularly in those individuals with low vitamin D status and accumulating evidence suggests that there is an association between low vitamin D status and COVID-19 severity and mortality.
13:00: Magnesium might not be the first nutrient that you think of for immune function, but it is involved in over 600 enzymatic reactions in the body, including those contributing to inflammation and immune responses. Magnesium is not well studied in COVID-19 patients, but there was one study that was published recently showing that up to 60% of critically ill patients in ICU have some degree of magnesium deficiency, and predisposing them to serious life-threatening effects.
Another nutrient to consider is our omega-3’s, our polyunsaturated fatty acids. They're modulating on the immune system and they're anti-inflammatory. They modulate migration, increase phagocytosis, they decrease cytokine production and the production of reactive oxygen species in nature. Meta-analysis has shown that omega-3 supplementation significantly improves outcomes in acute respiratory distress syndrome, and it results in shorter ICU stay, and the decrease in the use of mechanical ventilation. Importantly, omega-3’s are also beneficial for mood disorders, which are quite prevalent in this current pandemic. There was a study recently released saying that nearly 25% of individuals had either anxiety, depression or both. So omega-3 has these effects on both the immune system and also on our mood as well.
We can also look at specialised pro resolving mediators, which are formed from the metabolism of these omega-3’s and they are involved in resolving inflammation. So what they do is, they are involved in restricting the cessation of neutrophil infiltration, the counter-regulation of chemokine and cytokines, and the conversion of pro-inflammatory macrophages into anti-inflammatory macrophages. So this reduces inflammation and tissue damage and promotes resolution. What we're seeing is that co-morbidities such as diabetes and obesity, which are associated with COVID-19 have a disrupted lipidome, so they have altered levels of these lipid mediators and emerging studies demonstrate that this disrupted lipidome is associated with COVID-19 disease severity.
15:33: We know the gut microbiome is fundamental in the induction training and function of the immune system. And while we may think of COVID-19 primarily as a respiratory disease, there is mounting evidence to suggest gastrointestinal involvement. The SARS-CoV-2 virus can actually enter and replicate in human enterocytes. And the virus is detected in up to 50% of fecal samples. There have been several studies looking at the microbiome in COVID-19 patients. And what has been found is that there is a decrease in commensal bacteria and an increase in pro-inflammatory type bacteria and pathogenic bacteria as well.
And it's not just the gut that has its microbiome. That lung has a micro biome as well, and plays a protective role in immunity. The crosstalk between the gut microbiota and the lungs is referred to as the gut-lung axis. And it's bi-directional so gut microbial metabolites can impact the lung through the blood. And when inflammation occurs in the lung, it can affect the gut microbiota as well. So there really is a role to improve the gut microbiome in COVID-19 through diet, through the use of pre and probiotics.
16:52: Now, physical activity also has positive effects on our immune system. There've been a lot of studies looking at the effects of exercise, particularly in the elderly, and it's shown that it has multiple effects on the innate and adaptive immune systems. For example, it lowers concentrations of circulating pro inflammatory biomarkers and improves neutrophil chemotaxis, natural killer cell cytotoxicity and bacterial phagocytosis. And the immune effects are mainly through the release of interleukin 6 from skeletal muscles. So when it is released from skeletal muscle during exercise, it’s actually anti-inflammatory as opposed to under normal circumstances where it is inflammatory. Now exercise is dose dependent. So there have been studies, particularly in marathon runners, showing that intense physical activity can increase the risk of upper respiratory tract infection. However, overall, and this is a meta-analysis at 55 studies, has shown that habitual physical activity is associated with a 31% risk reduction of community acquired infectious disease.
18:08: Sleep is also very important for our immune resilience and it's not just the amount of sleep. It is actually our circadian rhythm as well, because immune cells exhibit circadian rhythmicity. So undifferentiated naive T-cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep and circulating immune cells with immediate effector functions, so our natural killer cells, and anti-inflammatory cytokine activity peak during the day. And it also affects vaccine efficacy, which is very interesting as this vaccine program gets rolled out for COVID-19. Morning vaccination for influenza resulted in a greater antibody response compared to those vaccinated in the afternoon.
18:57: Ideally, we would support our sleep through sleep hygiene, but sometimes you may need additional nutrients or herbs to assist with sleep. And one of these is melatonin, and melatonin is interesting because not only does it have positive effects on sleep, but it is also an antiviral, antioxidant and anti-inflammatory so a really good one for these times of the COVID-19 pandemic.
Stress is another key factor that may affect our immune resilience and stress at any point in our lifespan, even in utero. And in utero exposure to stress has been shown to reduce natural killer cell activity and T-cell activity in adolescents, it's been shown to increase the risk of childhood infection, and also been shown to drive T-cell immunosenescence in young adulthood. So we can reduce our stress by things such as meditation and yoga. And in human clinical studies, both yoga and meditation have been shown to have effects anti-inflammatory effects. They improve cell-mediated immunity. Meditation reduces biological aging by increasing telomerase activity and yoga improves mucosal immunity.
We can’t overlook the effects of socialized isolation, which is a huge issue that we've faced over the last year. And social isolation can increase the risk of disease and mortality.
20:29: So we need to practice prosocial behavior, find ways to reach out and connect with people. And whether that be through connecting, helping, sharing, donating, cooperating, and even volunteering. And prosocial behaviour, it improves happiness and psychological wellbeing, our physiological health, we have better physical functioning and it also decreases morbidity in medical populations.
And last but not least, we can't overlook the effects of the environment on our immune resilience. So pollution accounted for nearly 9 million premature deaths in 2015 with air pollution accounting for about 50% of those. And it's the airborne particulate matter, in particular, which has been shown to increase the viability of the SARS-CoV-2 infection. And there was a recent study that found that particulate matter with a size of 2.5 micrometres was a major contributor to COVID-19 cases in England, as an increase of one milligram per cubic meter in the long-term average of this particulate matter was associated with a 12% increase in COVID-19 cases.
21:46: So in summary, while our immune resilience relies on many factors, including diet and lifestyle, it ultimately relies upon the health and resilience of our planet as well. The emergence and spread of the SAS-CoV-2 virus appears to be related to things like urbanisation, habitat destruction, live animal trade, intensive livestock farming, as well as climate change and air pollution. So the COVID-19 crisis highlights the links between environmental change and the emergence of infectious disease. So we really do need to support not only our own resilience, but the resilience of the planet. Our resilience is a global process.
Thank you very much for joining me today.