How Dreaded Covid Inflammation Is Intensified by Age and Chronic Illness

Covid inflammation

Covid inflammation is a dominant factor that is addressed in my forthcoming Covid Immunity course. What follows is one of 15 lessons from the course, sans video. I posted it here so you may get a feel for it prior to its release. Like this one, several lessons from Protocol 2 focus on reducing baseline inflammation, a key objective in shielding you from infection, or if infected, protecting you from getting severe, inflammatory-provoked illness.

 

Covid inflammation

Lesson 10: Reduce Baseline Covid Inflammation by Addressing Age and Comorbidity Risks

Lesson 10 objectives:

  • To determine if your pre-existing health issues (comorbidities) or your age make you vulnerable to the novel coronavirus. 
  • To address the vulnerabilities by implementing the relevant lifestyle factors and nutraceuticals already covered in Protocol 2, and those to be discussed here.

Action Items:

  • If you have any of the comorbidities reviewed in Lesson 10, redouble your effort to prevent infection as detailed in Protocol 2.
  • Consume the Nutraceuticals reviewed.

Welcome to Lesson 10, the last lesson in Protocol 2.

The lessons in Protocol 2 have all been about prevention. The overarching goal is to protect you from getting infected, but if infected, to help ensure that your body’s immune system is well prepared to minimize any potential COVID-19 illness.

If you have no health issues and are under 50 years of age, the lessons reviewed so far will go a long way to help protect yourself from infection and illness. This is also true for those over 50 and have have the comorbidities addressed below. In that case, consider taking the nutraceuticals covered in Lessons 14 and 16, especially at the first sign of infection.

Your risk of getting infected with SARS-CoV-2 and then getting very sick from COVID-19 illness can get substantially higher if you have a number of pre-existing conditions, referred to as “comorbidities”, or if older than 50.

Let’s address comorbidities first, and then discuss how and why Covid gets more and more nasty the older we get.

 

Comorbidities Make You Vulnerable

Surveillance data reported to the CDC from health practitioners in the United States indicate that COVID-19 can lead to severe outcomes in older adults, and those with underlying health conditions. This has been reported throughout the world.

For instance, in the U.S., hospitalizations were six times higher, and deaths 12 times higher for COVID-19 patients who reported having cardiovascular disease, diabetes and chronic lung disease. [1]

But those three aren’t the only comorbidities that make COVID-19 worse.

According to the CDC, nearly 90% of patients hospitalized with COVID-19 had one or more underlying health conditions, including hypertension, obesity, chronic lung disease, diabetes and cardiovascular disease. [2]

Here’s the breakdown:

Covid inflammation is exacerabeted by comorbidities

A Time Magazine report underscored these findings and published more details. Let’s take a look:

These health issues have been deleterious even without the threat of Covid inflammation.

Let’s look at the prevalence of the five top comorbidities that are wrecking the health of so many people, and drive an above average percent of SARS-CoV-2 infections and COVID-19 health issues.

Cardiovascular diseases:

  • Cardiovascular diseases are the number 1 cause of death globally: more people die annually from Cardiovascular diseases than from any other cause.
  • An estimated 17.9 million people died from Cardiovascular diseases in 2016, representing 31% of all global deaths. Of these deaths, 85% are due to heart attack and stroke. [3]

Hypertension (elevated blood pressure):

  • An estimated 1.13 billion people worldwide have hypertension, most (two-thirds) living in low- and middle-income countries.
  • In 2015, 1 in 4 men and 1 in 5 women had hypertension.
  • Fewer than 1 in 5 people with hypertension have the problem under control.
  • Hypertension is a major cause of premature death worldwide. [4]

(It appears that the hypertension data relative to Covid risk appears both in the cardiovascular and renal disease categories.)

Diabetes:

  • The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014.
  • The global prevalence of diabetes among adults over 18 years of age rose from 4.7% in 1980 to 8.5% in 2014.
  • In 2016, an estimated 1.6 million deaths were directly caused by diabetes. Another 2.2 million deaths were attributable to high blood glucose in 2012. [5]

Lung Disease (or Chronic obstructive pulmonary disease — COPD):

  • Most COPD comes from smoking, second-hand smoke or long-term asthma.
  • The Global Burden of Disease Study reports a prevalence of 251 million cases of COPD globally in 2016.
  • Globally, it is estimated that 3.17 million deaths were caused by the disease in 2015. [6]

Obesity:

  • Worldwide obesity has nearly tripled since 1975.
  • In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese.
  • 39% of adults aged 18 years and over were overweight in 2016, and 13% were obese. [7]

It’s been established that those five major comorbidities negatively affect positive health outcomes from Covid. The relevant question is:

How can those with any of these health issues reduce their risk of serious Covid complications?.

Slow and steady is the way to go. You’re not going to make whatever ails you evaporate overnight. That’s the bad news. The good news is if you apply yourself consistently to the solution, it will typically take less time to get rid of the chronic disease than it took for it to become chronic.

All the suggestions made throughout Protocol 2 will be profoundly helpful in reducing any of the comorbidities mentioned, especially exercise and diet — and that’s because they all focus on reducing inflammation.

Chronic disease and the acute threat of Covid are mechanistically conjoined through Covid inflammation. Obesity, diabetes, obesity and cardiovascular diseases induce systemic inflammation, and are promoted by it.

Such dysfunctional inflammation does three things:

  1. It impairs the body’s capacity for the functional inflammatory responses that are the hallmark of immunity.
  2. At the same time, it enables misdirected, unbalanced immune responses, such as the now notorious “cytokine storm.”
  3. And this results in damaged endothelium, the inner lining of our vast network of blood vessels, putting every organ-system at risk, and explaining the perplexing spectrum of Covid complications.

So, if you have any of the comorbidities I’ve discussed, you have no greater incentive than this pandemic to get focused on making yourself healthier.

Everything I covered in Protocol 2 will contribute to you improving the chronic illnesses that make you vulnerable to Covid. But of course that can only happen if you act on them.

And now we come to the granddaddy of them all when it comes to Covid complications — your age.

 

The Vulnerability of Age and Covid Inflammation

Covid inflammation is a risk associated with aging

The older we get, the more  vulnerable to the virus we get, because our immune system becomes compromised. Older people produce fewer new T and B cells, which means they have less of these cells available to fight new, unfamiliar viruses that they haven’t encountered before.

There’s also a delay in the intercellular signalling between immune cells as we age. A 72-hour delay in T cell response can be fatal in fighting something like the novel coronavirus, which replicates quickly inside the body.

Older people also tend to have a higher base level of cytokines in their bodies, and they also experience more comorbidities. Pre-existing conditions like diabetes or heart disease can cause a higher baseline of cytokines in the elderly. The older you get, the more time chronic diseases have to become acute, and thereby damage your health and resilience against infection and diseases of any kind.

Given this, it’s unsurprising that the older you are, the more likely you would need to be hospitalized if you got infected with SARS-CoV-2.

If you check out the CDC’s COVID-19 hospitalization rate across age groups graph, you’ll see that there’s a big jump between those 65 and older, those 50 to 64, those 18 to 49.

Unfortunately, like many of our biological systems, the innate and adaptive immune systems become less robust as we get older.

The aging human immune system is characterized by two key changes:

  • An increase in innate immune responses or chronic inflammation — commonly referred to as “inflammaging”, given the close association between aging and systemic (chronic) inflammation.
  • A decrease in adaptive responses — referred to as “immunosenescence”, which is a gradual deterioration of the immune system.

It appears that a key factor in determining a poor prognosis during COVID-19 is a hyperactive innate immune system (Covid inflammation), and that possibly explains the increased complications experienced by older adults who get the disease.

An overactive innate immune response to a pathogen that leads to excess inflammation is a characteristic of aging, and of the chronic diseases of aging. This leads to damage to inflamed tissues and decreases the elderly’s resilience to infection.

Then there’s the matter of your thymus.

The Thymus Shrinks As We Age

The thymus gland makes white blood cells called T-lymphocytes, or T-cells, that fight infection. These T-cells are at the core of adaptive immunity. T-cells function to actively destroy infected cells, as well as to signal other immune cells to participate in the immune response.

The problem is that the thymus starts to shrink after puberty.

Here’s where your thymus is located:

The following illustration is an accurate depiction of how a thymus shrinks as we age. There’s not much left by the age of 50, just a lot of fat — referred here to as adipose tissue — where there used to be thymus tissue.

Less thymus means fewer T-cells are made (the “T” in T-cells refers to the thymus). This is one reason that SARS-CoV-2 infection rates are correlated with thymus shrinkage, which is correlated with age. [8]

The number of B cells also declines as we age. B cells produce antibodies against the antigens. And both T and B cells can turn into special memory cells that learn how to fight certain viruses.

Memory T and B cells are created specifically for each infection and can wipe out any reinfection of that particular virus or bacteria before it creates a problem in the body.

Another vulnerability in the immune system of older people is that with age immune cells seem to have a delay in their ability to communicate with one another. It’s unclear why this occurs, but a 72-hour delay in T cell response can be fatal in fighting something like the novel coronavirus, which replicates and spreads quickly inside the body. [9]

Older people also tend to have a higher base level of cytokines in their bodies, which rapidly increase as they continue to age. The comorbidities we reviewed can also cause a higher baseline of cytokines in a person’s body

The Young vs Aged Immune Response to SARS-CoV-2

Before I touch on what you can do that specifically addresses some of the vulnerabilities of age, I want to review the difference between how a young and aged immune system reacts to a SARS-CoV-2 infection.

Ineffective clearance of SARS-CoV-2 infection
in the aged respiratory system.

Rising Covid inflammation is a big risk for the elderly

The above image comes from a 2020 study that illustrates the difference between how a youthful and aged immune system reacts to a SARS-CoV-2 infection. In the youthful system, the infected alveolar cells are recognized and handled by the macrophages or dendritic cells (not pictured), and the rest of the arsenal of immune cells and molecules.

In the aged system, the viral alert signals are initially slow, resulting in greater viral replication. Cytokine signaling has yet to occur. This leads to greater viral replication and spread than the youthful system.

Click here for a full description of the youthful vs aged immune system.

The SARS-CoV-2 virus binds to ACE2 protein enzymes on airway epithelial cells in the upper respiratory tract. Epithelial cells tissues or cells are one of the most important cells found in the human body. The skin is made up of epithelial tissues. And most of the organs and the openings in the inner body are lined with epithelial cells.

So, the virus enters the cells and replicates (top left), which alerts the immune system. Viruses then travel to the alveoli — which are the tiny air sacs in your lungs that take up the oxygen you breathe in — and infect type 2 pneumocytes, which are cells found in the alveolar wall.

In the youthful system (lower left), the infected alveolar are recognized by alveolar macrophages (AMs) or dendritic cells (not pictured) that release cytokines and present antigens to T cells and other adaptive immune cells.

Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. They can be both pro-inflammatory and anti-inflammatory. When released, they signal the immune system to do its job.

Antigens are substances typically on a pathogen’s surface that are capable of stimulating an immune response, specifically activating lymphocytes, which are the body’s infection-fighting white blood cells.

T cells are a type of white blood cell, or lymphocyte, that can have the appropriate receptors to recognize and bind to the antigens, as well as activate other lymphocytes or directly kill infected cells, thus helping to prevent the spread of the virus.

Neutrophils are a type of white blood cell that is central to our innate immune defense. They act as the first-line responders to infection, attacking bacteria, viruses, and other pathogens.

They migrate to the sites of infection to clear infected cell debris.

In the aged system (top right), things don’t work so well.

Here the viral alert signals are initially slow, resulting in greater viral replication. You can see in this depiction that there are more viruses seeking to hook up with ACE2 receptors, and cytokine signaling has yet to occur.

Defective macrophages (which are supposed to goggle up infected cells) and T cells that have a limited repertoire of receptors in aged systems are less effective (lower right). More cells get infected, inducing high levels of inflammatory cytokine signaling in the lower respiratory tract.

The cell lining of small blood vessels become inflamed, fibroblasts are activated, and SARS-CoV-2 viral components and cytokines enter the bloodstream.

Fibroblasts are cells that manufacture and maintain connective tissue, the structural framework that supports the organs. Unfortunately, in this instance they’re inflammatory.

What then happens is fluid fills the alveolus and reduces lung capacity.  The virus infects endothelial cells that line the capillaries and small veins throughout the body in other organs. A cytokine storm then initiates clotting in small blood vessels, causing severe hypoxia (low oxygen), excessive bleeding or clotting, and organ failure.

 

Strengthen the Aged Immune System

Fortunately, there are positive steps you can take to push back the immune system limitations that can occur with age. The quickest way to improve aged immunity is to make the lifestyle changes already addressed in Protocol 2. Importantly, you can also work to reduce the number of senescent cells in your body.

The older we get, the more senescent cells we get, and that’s not a good thing for at least two big reasons:

  1. Senescent cells secrete release pro-inflammatory cytokines and numerous other harmful chemicals that can damage DNA, promote chronic inflammation and contribute to systemic aging; and
  2. Senescent cells have lots of receptors on them that SARS-CoV-2 can attach to and thereby infect those cells.

What’s been shown to selectively eliminate senescent cells is a class of drugs and supplements called senolytics. To get a bead on that, I encourage you to read two articles I’ve written pertinent to age and Covid:

Here’s Professor Michael Lisanti’s three-minute video from the Aging Immune System article.  Be sure to watch where he describes a big reason why older people are vulnerable to Covid.

INSERT

 

If you watched the video, you know it has to do with senescent cells. Cell senescence is a phenomenon by which normal cells stop dividing. These cells don’t die when senescent, but they’re  not fully alive either, which is why they’re referred to as “zombie cells”.

UPDATE (5/7/22): As I explain here, a new study casts shade over the effectiveness of fisetin as a senolytic.

Three off-the-shelf senolytic supplements you can get are:

  • Fisetin, a flavonoid and antioxidant
  • Quercetin, a plant polyphenol from the flavonoid group
  • Piperlongumine, a natural product derived from the fruit of the Asian Long pepper

The highest fisetin-containing food is strawberries. It’s also found in small amounts in apples, grapes, persimmons, Kiwi fruit, onions and cucumber.

We’ve already covered quercetin, which you can get from from capers, onions, asparagus, lettuce and berries, as well as from many other fruits and vegetables, but in smaller amounts.

Piperlongumine is an extract of the fruit of the long pepper, a pepper plant found in southern India and southeast Asia. So that would be your food source for it.

Although you can get these three senolytics from food, it’s unlikely you’ll get the needed concentrations to reverse a high baseline level of inflammation that’s typical in seniors and people with comorbidities; therefore, you would need to supplement with these senolytic compounds.

Like all the nutraceuticals that I tell you about in this course, the effectiveness of these three senolytics is supported by good scientific studies:

A study published in 2018 about fisetin makes the conclusion that “fisetin was the most potent senolytic” of the 10 tested, and also mentions the conclusion of a previous study these researchers did that showed quercetin to be a potent senolytic as well.

A study published in 2017 that addresses all three of these senolytics concludes that all of them appear to have strong potential for becoming orally-active senolytic agents for clinical use.

 

Assess Your Covid Risk

Now I want to share with you two ways to assess your risk for Covid infection based on age and health.

  1. The first is the Covid Age Risk Calculator tool developed by Everist Health, a health tech company. Use this to get a sense for your risk to Covid.
  2. The second risk assessment is called the Age vs Health Covid Risk Matrix developed by a highly respected Covid expert named Dr. David Katz.

Use the risk calculator to quantify your risk, and then the risk matrix to inform yourself what to do to mitigate that risk. I explore these Covid risk assessment tools in greater depth in the Lesson 10 video.

 

Your Takeaway re Covid Inflammation, Comorbidities and Age

Remember this about the effect of comorbidities and age on SARS-CoV-2 and COVID-19:

  • 90% of patients hospitalized with COVID-19 have one or more underlying health conditions, including hypertension, obesity, chronic lung disease, diabetes and cardiovascular disease.
  • Chronic disease and the acute threat of Covid are mechanistically conjoined through inflammation.
  • Dysfunctional inflammation:
    • It impairs the body’s capacity for the functional inflammatory responses that are the hallmark of immunity.
    • At the same time, it enables misdirected, unbalanced immune responses, such as the now notorious “cytokine storm.”
    • And this results in damaged endothelium, the inner lining of our vast network of blood vessels, putting every organ-system at risk, and explaining the perplexing spectrum of COVID complications.
  • The aging human immune system is characterized by two key changes:
    • An increase in innate immune responses or chronic inflammation — commonly referred to as “inflammaging”, given the close association between aging and systemic (chronic) inflammation.
    • A decrease in adaptive responses — referred to as “immunosenescence”, which is a gradual deterioration of the immune system.
  • Improve chronic health issues with an anti-inflammatory diet and exercise.
  • Improve inflammaging and immunosenescence with senolytics.

 

 

Last Updated on November 11, 2022 by Joe Garma

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Joe Garma
 

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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