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Introduction
When the pandemic hit in the early part of 2020, the world was dealing with an unknown virus. As of today, 56,236 peer-reviewed research papers have been published on COVID-19. We know so much more.
In this piece, we briefly review normal immune responses, abnormal immune responses, and the opportunity lifestyle medicine offers all of us to improve immune resilience. Why is this important now?
Top-down epidemiolgiocal modelling of the virus has its place for public policy, as long as it uses approriate assumptions. Bottom-up understanding of how our biology responds to the virus is vital from a personal wellbeing perspective. Education is king.
Coronavirus disease 2019 (COVID-19) is a disease caused by SARS-CoV-2. What follows is an overview of how the body becomes infected, our immune response to SARS-CoV-2 in both healthy and abnormal situations, and the lifestyle implications this brings.
SARS-CoV-2
SARS-CoV-2 belongs to the family of Coronaviruses. Coronavirus includes several species capable of infecting various animals, and some of which also affect humans.
SARS-CoV and MERS-CoV had a low level of transmission, but a high level of lethality. SARS-CoV-2 is easier to spread compared to former coronaviruses, but it is not as lethal. A September 2020 systematic review estimated worldwide infection death rate of 0.68%. However, this number will change over time as data collection improves. Death rate appears to be primarily dependent on age and underlying health status.
Research suggests that nearly 80% of all infections remain undocumented because patients are either asymptomatic or present with very mild symptoms.
SARS-CoV-2 incubates for an average of 5.8 days. Incubation represents the time in days from the point of COVID-19 exposure to the onset of symptoms.
Upon entry into cells, viral RNA from SARS-CoV-2 gets released into the cytosol, and the virus exploits the cell machinery to replicate. The rapid viral replication causes cell damage, the release of pro-inflammatory cytokines, and the recruitment of inflammatory cells.
How Novel Is This Coronavirus?
Early in the pandemic, public health officials were unsure how the immune system would respond to SARS-CoV-2, and if a level of immunity was even possible after infection. This concern may have formed one of the assumptions behind initial lockdown strategies. We now understand a lot more about the virus, and the body’s response to infection. Two takeaways are essential here:
First, research shows that the immune system does identify SARS-CoV-2.
Second, it appears we also have a level of pre-existing immunity. At least six studies have reported T cell reactivity against SARS-CoV-2 with no known exposure to the virus.
A paper published in the prestigious journal Nature found SARS-CoV-2-reactive T cells in at least 35% of unexposed healthy individuals. The authors of this study concluded by saying:
Our study reveals pre-existing cellular SARS-CoV-2-cross-reactivity in a substantial proportion of SARS-CoV-2 seronegative healthy donors. This finding might have significant epidemiological implications regarding herd immunity thresholds and projections for the COVID-19 pandemic.
SARS-CoV-2 may be novel, but our immune system does an excellent job of recognising it.
A Healthy Immune Response to SARS-CoV-2
First Line of Defence: Innate Immunity
The first line of defence against SARS-CoV-2 is the innate immune system. Mucosal immunity refers to the production of mucus, designed to trap viral particles, be swallowed and eliminated via the gastrointestinal tract. If this barrier gets breached, there is another line of defence involving pattern recognition receptors (PRRs).
PRRs are like reconnaissance soldiers. They look for “stranger and danger” recognising different molecular structures characteristic to SARS-CoV-2. PRRs identify known viruses, bacteria and other types of pathogens that humans have had over many millennia.
PRRs recognise the SARS-CoV-2 virus and begin the inflammatory response via signalling pathways, such as NF-kB. The result is the activation of various cytokines, such as IL-6, TNF-a and IL-1b.
You can think of these cytokines as the troops. They attack and kill the virus. They are also crucial in communicating with the adaptive immune system so that we develop appropriate antibodies, and with it, the potential prevention of reinfection to SARS-CoV-2 in the future.
Second Line of Defence: Adaptive Immunity
The adaptive immune system helps to build memory and future immunity against the virus. T cells are hugely crucial in long-term immune resilience to SARS-CoV-2:
– CD4+ T cells stimulate B cells to produce SARS-CoV-2-specific antibodies
– CD8+ T cells target virus-infected cells and kill them with cytotoxic molecules, such as granzyme A
80% of the infiltrating cells in COVID-19 are CD8+ T cells.
It is worth noting that current estimations of community immunity cited by many in the medical community refer only to B cell SARS-CoV-2-specific antibodies. However, this approach ignores the role of sIgA and T cells in generating a level of immunity and protection against the virus.
For example, a study into the original SARs-CoV virus found that six years after the virus, there were no SARs-CoV-specific B cells detectible in 91% of patients. However, there were SARs-CoV-specific memory T cells present in 61% of the SARS survivors studied.
In the image below you can see the difference between normal and abnormal responses to COVID-19:
An Unhealthy Immune Response to SARS-CoV-2
Given the capacity of the immune system to target, kill, clear and remember SARS-CoV-2 for future protection, what happens in the immune system to cause poorer outcomes with COVID-19? Let’s look at the innate and adaptive immune system in this situation.
Abnormal Innate Immune Response
First, suppose the innate immune system is not functioning correctly due to chronic illnesses, such as obesity, type II diabetes and cardiovascular disease. In that case, patients can experience the well-known “cytokine storm”.
A “cytokine storm” results from a sudden acute increase in circulating levels of different pro-inflammatory cytokines including TNF-a, IL-6, and IL-1b. Think of it as meta-inflammation in action, and way too many marines going to the site of infection causing huge collateral damage. The cytokine storm can cause lung injury, viral sepsis, pneumonitis, ARDS, respiratory failure, shock, and organ failure.
Abnormal Adaptive Immunity
Second, in response to the cytokine storm, the adaptive immune system can also go awry. Lower numbers of T cells, such as CD4 and CD8 T cells, have been found in detected in patients infected with SARS-CoV-2 with worse outcomes. The number of T regulatory (Treg) cells are also significantly decreased in severely ill patients. Regulatory T cells are vital in the maintenance of immune homeostasis: a balanced and effective immune response.
Lifestyle Medicine Implications
Understanding healthy and abnormal immune responses to COVID-19 is important. It enables us to stand back from the noise and establish our risk factors, and take control of certain lifestyle variables accordingly.
For most, poorer outcomes with COVID-19 occur in those individuals who are already experiencing high levels of inflammation. COVID-19 and the cytokine storm is a meta-inflammation process. When you look for a common theme linking obesity, cardiovascular disease, COPD and other groups of people with poorer outcomes with COVID-19, it is the preexistence of chronic inflammation.
For example, CRP (a common generalised inflammatory marker that shows up on any blood test with your GP/doctor) quite literally predicts COVID-19 outcomes. The odds ratio of someone with high CRP being admitted to ICU in the hospital is 7.09. This is not something to be scared of: it is something to take action on.
Preventative lifestyle measures have never been more critical in helping our immune system manage COVID-19 infection. Given that the virus is now endemic in society and here to stay, proactive wellness takes on new levels of importance.
Diet, exercise, and other anti-inflammatory lifestyle changes can have a transformational effect on risk factors with COVID-19. This insight should be celebrated and shared, especially given the existing mental health crises caused by fear and a perceived lack of control.
Gut Health: Research shows that the higher the levels of a circulating pro-inflammatory cytokine called IL-6, the worse the outcomes for COVID patients. Lifestyle-induced imbalances in the gut are triggers for IL-6. Excess stress, a high-fat diet and too much alcohol can trigger dysbiosis and increase circulating IL-6.
Probiotics may be an important weapon in helping individuals to successfully adapt to SARS-CoV-2 infection. This can be seen below from a recent paper addressing the potential effect of Lactobacillus rhamnosus CRL1505:
Diet: It well established that a whole food nutrient-dense diet reduces chronic low-grade inflammatory markers across the board. Working from home provides each of us with the opportunity to eat more wholesome foods to look after our immune resilience.
If you are interested in learning about potential strategies to improve your nutrition to support immune resilience during this time, this is a useful research paper.
Exercise: Research also shows that exercise helps to reduce chronic inflammatory markers, such as CRP, thereby improving the chances of a positive outcome after SARS-CoV-2 infection.
