Now a one hour zoom conference on the immune system and health and wellness
It is our first month into social distancing measures. We have had a few months to see and read about how the pandemic affected some countries, challenging the health systems of Italy and China. We now witness the effect of the pandemic in New York City, while the case loads increase in other cities. Hospitals have struggled to find beds, personal protective equipment, and ventilators. Healthcare workers are being stretched to their breaking point to care for sick patients.
As of April 15, of the 644,089 cases in the United States, 28,529 people have died from COVID-19. It is a sad reality that more people will succumb to this infection.
We grapple with the paradox, that some will develop severe disease, while the majority of people will have only mild disease. A closer look at the risk factors of those most affected by COVID-19 does allay some fears. As with all infections, advanced age (>65 years, especially >75 year of age) is the greatest risk factor. Nevertheless, we are more than chronologic age. Underlying conditions often increase with age, including obesity, hypertension, diabetes, lung disease, and immunocompromising conditions are important underlying risk factors.
What explains these exceptional cases, e.g. a thirty year old female with no other health problems who dies from COVID-19 after having a severe presentation? The news media covers these cases, because they are mysterious and show that this process can be severe. We learn about the way the body interact with the virus, and we begin to realize that a person with “who was otherwise healthy” was a person who has risk factors that haven’t been determined. Recent studies have brought light to genetic susceptibility for more severe infections, such as single gene polymorphisms and HLA variance.
Unfortunately, news reports can stoke further fears. We as humans are wired to consider these exceptional cases over what is more likely, a cognitive distortion known as catastrophizing. Our minds weigh risks and predict ways we should react to this unseen, approaching threat. It is as if our brain fixates on these negative outcomes to trigger an action. A result of this is to go into “fight, flight or freeze mode,” and, since we can’t fight an invisible enemy, it often manifests as “waiting out the pandemic.” Enter some new routine like netflix binge watching, eat your cravings, nod off and repeat.” These behaviors put us as risk for becoming unhealthy.
There are some active ways that we can become more resilient through this and protect ourselves from severe disease. Although we are not able to change our age, inherited chromosomes, and there is no fountain of youth. Nevertheless, we can protect ourselves from severe infections through daily healthy decisions. The burgeoning field of epigenetics shows that diet, stress and sleep affect genetic expression and our immune systems.
What follows are some strategies to protect one from more severe COVID-19 disease during the pandemic:
- Get plenty of sleep.
- Keep physically active.
- Keep stress levels low.
- Keep a healthy weight.
- Eat a nutritious diet.
- Avoid or limit medications that can affect the immune system.
- No smoking or use of alcohol, marijuana and other drugs.
1. Get plenty of sleep. “Sleep helps healing”
The quarantine has altered, sometimes drastically, our normal routines. As we adjust, some people working from home may compromise a healthy duration of sleep to get more work done in the evening. Others may look at the schedule change as a vacation and become more lax with their routine.
Sleep deprivation can lead to impairment of immune activation, of both innate and adaptive immunity. The innate immunity is the body’s first line of defense against a virus. There are likely hormonal factors (e.g elevated cortisol) that contribute to these changes. Decreased sleep leads to impaired activation of the immune system and increased inflammation. In one study, pro-inflammatory cytokines IL-6 and TNF-alpha receptor 1 were increased after four days of sleep deprivation.
In one study of 153 men (ages 21-55), sleep duration less than 7 hours and decreased sleep efficiency (<92%) were associated with a 2.94 times and 5.5 increased risk of acquiring rhinovirus than those who slept greater than 8 hours and had >98% sleep efficiency. A good night’s rest improves the body’s immune response, allowing better NK cells capacity and T cells to migrate to infected sites and lymph nodes. Adequate sleep ensures that cytokines, which are cell signaling agents, function adequately to interact with T-helper cells.
Sleep disorders such as sleep apnea or primary insomnia can decrease efficiency of sleep and lead to health risks. It is important to discuss with your doctor if you have frequent sleeping problems, whether it is getting to sleep or staying asleep. Other signs can include decreased restful sleep, feeling tired early in the day, “caffeinating” possibly more than 2-3 cups reaching for alcohol or sleeping pills at night. Other signs include lower extremity swelling, frequent nighttime urination, dry mouth in the night, night sweats and morning headaches.
Action: As for the quarantine, ensure that you are sleeping a consistent duration at consistent times. Refer to the prior articles on sleep for more details (The Scoop on Sleep, Sleep Disorders Patient Education).
2. Keep physically active
Regular exercise strengthens and conditions the body and provides richly oxygenated blood to all of its cells.. Physical activity leads to a reduction of the stress reaction and enhances sleep. Rapid increases in Natural Killer (NK) cells were found after exercise secondary to norepinephrine release. Exercise essentially lowers systemic inflammation.
Regular activity requires increased effort during this time of quarantine, as devout gym-goers have lost their routine. A consequence of closing the gyms and other exercise centers during this time of social distancing could be an increase in physical deconditioning, falls, and weight gain. These could exacerbate chronic health conditions in some people. It is therefore important to attempt to maintain the intensity of your exercise regimen while at home. Kenneth Powell et. al. have published a general guide to exercise, which supports that “some activity is better than none and more is better than less.”
Action: Set aside some time each day to walk or job outside, to stretch your back and legs, and to do some mat exercises with light weights at home. There are multiple online options and apps, if your looking for some motivation.
3. Keep levels of Stress Low
Stress hormones, such as cortisol, epinephrine and norepinephrine, are released in a fight or flight perceived or real situation or with sleep deprivation. These hormones can lead to T-cell dysfunction and leukocyte adhesions molecules which allow T-cell to traffic to sites of infection. Exercise and meditation will likely reduce one’s reaction to stress and lead to decreased cortisol secretions.
Stress attenuates the immune system. In studies of medical students undergoing a short-term 3-day period of examinations (J. Glaser and R. Glaser), there were levels of decreased natural killer cells, a part of innate immunity, during the times of the exams. The researchers found less gamma interferon activity and T-cell response in test tubes. Even with chronic mild stress or depression, there may be an impact on the lymphoctye-T cell response to mitogens (things that normally activate the immune system directly).
What can we gather from this information? The immune system reacts to hormones that are produced in the stress state, inlcuding cortisol, norepinephrine and epinephrine. Immune cells possess receptors that interact with these hormones. Self-management of stress with resilience practices such as physical exercise and meditation reduces the severity of this impact and keeps the immune system functioning at its maximum.
4. Maintain a healthy weight.
Healthy Weight is a Full System Benefit. Obesity is a chronic disease.
A healthy weight allows that body to function optimally and prevent multiple insults, including infections. It allows for an effective immune system to neutralize infectious particles and reduce the severity of disease process. As one becomes more overweight, the body becomes taxed by its attempt to compensate. This impacts the way the immune system functions as well. There was an association with high Body Mass Index results (BMI>35) and increase need for being hospitalized in the ICU or even death during the swine flu outbreak in 2010.
In a recent publication (Petrilli et al.) that evaluated the risks in 4,103 patients with COVID-19 disease in New York City, a body mass index (BMI) of greater than 40 correlated with a six-fold higher risk of severe disease (OR 6.2, 95% CI, 4.2-9.3). The only other risk factors that were higher was age >= 75 (OR 66.8) and age 65-74 (OR 10.9).
Let the message be clear: obesity is a chronic disease. Obesity can lead to acute and chronic inflammation. Occasionally, as an infectious diseases doctor, I have been asked to see someone for a chronically elevated white blood cell count. One common link is that the majority of these patients were significantly obese. Increased adipose tissue leads to a build-up of inflammatory hormones (adipokines), such as leptin, IL-6, tumor necrosis factor and resistin. Macrophages are recruited into adipose tissue and continue the response and inflammation. There may be some localized oxygen delivery issues into fatty tissue as well, known as hypoxia. There are impacts in both innate and cellular immunity. An already taxed body cannot develop a robust immune response.
We cannot talk about the parts without talking about the whole. Obesity leads to multiple systemic decompensations as the body attempts to compensate.
1) Increase adipose tissue leads to tissue hypoxia, macrophage infiltration and a pro-inflammatory state, as discussed.
2) Sleep deprivation from obstructive sleep apnea leads to cortisol hypersecretion, which is a potent immunosuppressant.
3) Chronic hypoventilation of the lungs increases the risk of pneumonia.
4) Aspiration of gastroesophageal reflux leads to an increased risk of pneumonia.
5) Long-term obesity can lead to liver and spleen disease, which impairs the immune system substantially.
6) Impaired glucose metabolism can lead to deficiencies in innate (antimicrobial peptides, natural killer cell activity) and acquired immunity (T-cell and B-cell immunity).
5. Eat a nutritious diet.
A healthy diet provides the ingredients through which a robust immune system is established. Every food that enters our digestive system requires the body to incorporate it through metabolic pathways. Ultimately, the metabolites of the food reach our vascular system, a network that connects to every cell in the body. Our immune system operates from this pathway
Certain foods can rev up our inflammatory response, which might disable as strong of an immune response to infection. Examples of these foods include ultra-processed high carbohydrate foods, refined flour, snack foods, French fries, fried foods, sodas, and red meats. Studies have shown increased levels of known markers of increased inflammation, including IL-6, IL-7, and TNF-alpha. A host of chronic medical conditions, including autoimmune disorders, irritable bowel syndrome, psoriasis and other dermatitis, diabetes, cardiovascular disease, degenerative joint disease, Alzheimer’s disease, and even anxiety and depression have been associated with inflammation.
A whole foods, plant-based diet is protective of inflammation and can “boost” the immune system. Vegetables are replete with vitamins and fiber that protect the body and optimize its functional state. As a general rule of thumb, mix up your diet with a rainbow of colors, vegetables, healthy grain fibers, nuts and fruits. Keep well hydrated with water. A healthy, well-balanced diet would include all of the nutrients, vitamins, and anti-oxidants to keep the immune system functioning at its best.
Vitamins and Nutrients
Although nutrient supplementation has not been studied rigorously in trials, there is support for vitamin D supplementation in infections. Vitamin D has a known role in the innate immunity including its role in inducing cathelcidins and defensins. Vitamin D is also involved in adaptive immunity and affets expression of T helper cells. During the winter in northern hemisphere countries, relative insufficiency of vitamin D results from decreased sunlight. So, it might be reasonable to take a vitamin D supplement available over-the-counter.
Zinc may be associated with inhibiting replicase (RNA-dependent RNA polymerase), an enzyme associated with viral replication of COVID-19, in an in vitro study. Studies have shown that chloroquine (and likely a related drug, hydroxychloroquine) may allow the zinc to enter into a cellular membrane (known as an ionophore). Whether this equates to some benefit as a supplement is not clear.
Vitamin C has an important role in the immune and vascular systems. A deficiency in vitamin C, a common occurrence in the age of maritime exploration, can lead to collagen defects that increased vascular fragility, delayed wound healing, bleeding, and even atherogenesis. Vitamin C has multiple effects on both the innate and adaptive immune system, including antioxidant properties, leukocyte (White blood cell) signaling (that improve wound healing), T-cell maturation and antibody generation. While vitamin C deficiency is exceedingly rare in modern times, fad diets and extremely limited diets seen in economic hardships, marginalized populations, and homelessness require its consideration. Interestingly infections could precipitate scurvy in already at-risk populations. Vitamin C stores are not long-lasting, so a diet replete with plenty of citrus foods will ensure that you are protected.
Action: Incorporate a palette of plant-based foods in your diet, such as vegetables, unprocessed grains, and fruits. These foods will provide an abundance of nutrients, vitamins and fiber. Supplementation with a multivitamin may be useful, but let it not replace the source. The food will fuel your system and lead to vascular health and a robust immune system.
6. Avoid or limit medications that can affect the immune system.
We live in a pill-taking society. More than a third of patients ages 62 to 85 take at least five prescription medications. What the pharmaceutical industry is studying for a “desired effect” or drug indication is an effect that causes some degree of destabilization in an already taxed system. Although, in the short run, these drugs may mitigate risks of a chronic disease, a pathway toward optimizing one’s health has the strongest benefit.
Medications can have direct or indirect effects on the immune system. Medications such as prednisone, cellcept (mycophenolate), imuran (azathioprine) can have a direct effect on the both innate and adaptive immune system, by impairing both B-cell (think antibodies) and T-cell (think killer T-cells) function.
Newer medications, known as monoclonal antibodies are directed toward T cell receptor (CD-3) and IL-2a and are associated with some degree of immunodeficiency. There may be an increased risk of activating TB in someone who has latent TB infection as well as Staph aureus infections possibly and other fungal infections. Whether an agent (Actemra, an IL-6 inhibitor) that is effective for rheumatoid arthritis may benefit those with severe COVID-19 is the subject of one study.
With the COVID-19 pandemic, several medication concerns have been raised. Some researchers hypothesized, that since SARS-CoV-2 enters Type 2 pneumocytes using ACE2 receptors (also found in the vascular system), medications that may lead to more expression of these receptors could cause a more severe presentation of COVID-19. These medications include ibuprofen, a type of diabetic medication (thiazolidinedione class) and ACE inhibitors, a type of blood pressure medication. Although more research is necessary to clarify this risk, the conditions themselves (high blood pressure, diabetes and heart disease) treated with these medications are risk factors for SEVERE COVID-19 disease. As for now, I would not advise someone to stop a medication to treat the condition that, if not treated, could increase the risk of severe disease. As for ibuprofen, infrequent use is probably with limited risk, but I wouldn’t recommend using this medication regularly anyways.
Action: Medications are a short-term measures that cause decompensation (ie. side effects) to get a desired effect. When one has a diseased condition, there is a state of decompensation that often affects multiple systems. The pathway toward disease mitigation (and health optimization) requires a healthy lifestyle.
7. No smoking and marijuana and limit excessive alcohol intake
If you are a smoker, NOW is the best time to quit. COVID-19 is a respiratory tract virus. In a recent article, a greater association of death and severe disease in smokers was found in multiple studies out of Wuhan, China. Zhang et al., found a 2 fold risk (Odds ration 2.23) of severe disease in smokers in a total of 140 patients, 58 patients had severe disease and 82 had non-severe disease. With severe: 3.4% were current smokers and 6.9% were former smokers; With non-severe: 0% current smokers and 3.7% former smokers. Liu et al. found a high proportion of smokers with smoking history (27.3%) who had a adverse outcome compared with 3% smoking history in those with improvement.
A smoker also has a three-fold higher risk of bacterial pneumonia than a non-smoker, and a two-fold higher risk of getting influenza. Tobacco paralyzes respiratory cilia (tiny hairs) movement, limiting the body’s natural ability to clear bacteria and other particles away from the lower respiratory tract.
It appears that therecommendations for alcohol 60% or stronger alcohol-based hand sanitizers were misconstrued as a way to treat the virus directly in the throat. As the COVID-19 cases surged in Iran, 44 people died from methanol poisoning after false rumors of its benefit as a “miracle cure” in treating the disease emerged. Keep the alcohol use for the hands, not for the system. There is likely no completley safe level of alcohol, with increasing toxicity with dose.
The immune system is affected from alcohol beginning with the gut microbiome and the gut barrier. As a result of this disruption, the liver becomes inflammed with increased fat deposition, or “fatty liver.” There is an increased risk of pneumonia, by increasing the risk of aspiration, altering ciliary function (an innate protective mechanism in the lungs), and altering the function of immune cells in the respiratory tract. The bone marrow can be injured at higher levels.
Action: Every substance that you put in your body has to be metabolized by the body to protect it from harm. Known toxins like smoking, alcohol and drugs impair the immune system as it impairs all aspects of a healthy body. Abstinence from these substances will provide optimal protection from a severe COVID-19 infection.
If you already have a chronic condition, there are ways to improve the situation…
Oftentimes, multiple chronic conditions emerge in the diseased state. Whether you have hypertension or diabetes, there are often some other emerging problems. Many times, a healthy weight can provide protection from these conditions. If your weight is not optimal, even beginning toward this direction can provide great benefits.
When we think of weight loss, we have to think of all of the systems in play. In many ways, a healthy is like being in an orbit. It is generated by largely a plant-based diet, an active lifestyle with daily exercise, and a low stress state and resilient mind. Action towards improving one of these areas generally begins to extend to the other areas to lead to a balanced state.
Action: Begin by adding plant-based foods in your diet. Think of the natural source of food (rather than various stages of processing). Developing a new routine is not always easy, but it always starts with a decision to take it one day at a time, one moment at a time, and one bite at a time. The impact on your diseased state can be dramatic and liberating.
Now a Zoom conference on the above: