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Address factors known to impact immunological risk for severe COVID-19 outcomes. Most of the
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integrity work of achieving optimal glycemic control involves
a. Sleep - Healthy sleep is anti-inflammatory and subtracting foods from the diet that contribute to an
promotes appropriate Th1 response. Disordered sleep increased post-prandial glycemic response. This
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is characterized by reduced sleep efficiency, less slow avoids adding to the burden of polypharmacy involved
wave sleep, and more REM sleep. Disordered sleep in implementing other tactics. While there is
yields increased inflammation and increases Th2 individual variation in what food cause a higher
response at the expense of Th1 response. glycemic response in specific individuals, the
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Sound sleep hygiene practices, reviewed general advice of reducing foods with a high glycemic
elsewhere, 140-143 are fundamental for promoting load is a good place to start. Food combining in
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healthy sleep. In addition, substances such as order to reduce glycemic burden should also be
melatonin may be added to enhance sleep promotion. considered. 162,163 By monitoring blood sugars using a
Not only is melatonin a useful sleep aid, it also continuous glucose monitor or intermittent
inhibits NLRP3 inflammasome activation, 144-146 and glucometers one can get a good sense of what types of
reduces airway inflammation. Melatonin has also foods increase postprandial glycemic response. 164
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been identified as a potential therapeutic drug in an d. Other Dietary Factors - Dietary factors in addition
in silico model of the human interactome with to those contributing to disrupted glycemic control
SARS-C0V-2 (4). should also be addressed. A high quality nutrient
b. Stress - As referenced earlier, stress chemistry is dense diet that focuses on eating whole plant-based
inflammatory and has been shown to shift the patient foods that are rich in healthy fats and phytonutrients
away from effective Th1 response. Many patients will (multicolored fruits and vegetables) is foundational
have been enduring significant chronic stress by the to decreasing overall inflammation. Reducing or
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time they become infected. Though it is not part of eliminating inflammation promoting foods is also
the main protocol, for patients with significantly important. Foods that are highly processed and/or
elevated stress levels, it may be useful to give contain chemical additives, trans-fats, oxidized fats
adaptogens like ginseng or ashwagandha. 148-152 and added sugars are inherently inflammatory. 166-168
Stress chemistry can and should also be addressed e. Lung and GI Microbiome - The lung microbiome is
by a number of other techniques that have proven closely linked to chronic lung diseases and lung
useful for decreasing the stress response. Patient inflammation in a bidirectional manner. 169,170
ability and personal preferences will guide the Disruption of gut microbiome can increase
appropriate choices. Techniques include mindfulness- sensitivity to viral infections, while treatment with
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based stress reduction (MBSR) 153,154 exercise, beneficial probiotics can enhance resistance to viral
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relaxing music, creative pursuits, biofeedback, and infection. The role of the gut microbiome in
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many others, reviewed elsewhere. overall inflammation has been well established. 173,174
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In addition, the lung and gut microbiomes both have
Eliminating non-purposeful inflammation an intimate relationship to their respective mucosal
Factors known to drive inflammatory activation, such membranes, which are critical players in early
as dysglycemia, dysbiosis, and/or consumption of immune protection. Therefore, maintaining a
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inflammatory foods need to be addressed. healthy lung and gut microbiome, and maintaining
Glycemic control, dietary factors, and Lung and GI the integrity of the mucosal linings of both systems
microbiome balance are all essential components of health is important in decreasing overall inflammatory
and essential areas of focus in the functional approach to burden. The use of a high fiber, polyphenol rich
patient care. In the Prevention Phase, addressing these diet, prebiotics, and probiotics can be considered to
systems may present a valuable opportunity to reduce the promote a healthy microbial ecosystem. 176-179
patient’s baseline inflammatory status (Figure 4). In the Avoiding smoking and air pollution also makes
COVID-19 setting, it’s essential to consider whether sense. 180,181
attention to these factors is a suitable area of focus, with Many of the vitamins, minerals, and botanicals
considerations including illness phase, patient capacities recommended in this paper for their immunological
to follow multiple instructions, and potential for an roles also have roles in supporting the microbiome and
intervention to affect short term positive impact on mucosal membrane integrity and immunity. Vitamin D
patient outcome. plays an important role in mucosal immune function
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c. Glycemic Control - Addressing glycemic control is a and vitamin A is critical in maintaining epithelial
critical part of controlling baseline inflammation. As barrier integrity. N-Acetyl Cysteine protects
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stated earlier, insulin resistance, and impaired glucose intestinal health via a number of different mechanisms
tolerance are associated with inflammation, and may including tight junction signaling. 184
be a contributing factor that puts diabetics at a higher

18 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print Yanuck—Immuno-physiological Approach to COVID-19