Page 15 - IMCJ19s1

inflammatory conditions. An opportunity presents Dysregulation of the balance of GI microbiome
itself in the non-infected patient (and potentially in bacteria has been shown to be a source of systemic
the infected patient early in the course of the disease) inflammation. 80-83 Intestinal metabolism of dietary
to reduce non-purposeful contributions to their level fiber and the resulting increase in short chain fatty
of inflammation, to mitigate the risk of the patient acids (SCFAs), specifically propionate, has been
entering the Escalating Inflammation Phase, should shown to enhance hematopoietic generation of
they become infected. Several potential areas of macrophages and DC’s seeding the lungs. The
interest should be included in the clinical inventory: DC’s had increased phagocytic capacity and
i. Sleep – Healthy sleep promotes T helper decreased capacity to induce Th2-bias in lung T
type 1 (Th1) cell response. Th1 cells secrete cells, an effect that reduced Th2 inflammation.
84
interferon gamma (IFNγ) that supports anti-viral Exacerbations of chronic lung diseases have
immune response. Disordered sleep promotes been proposed to be episodes of lung microbial
inflammation and Th2 response, at the expense dysbiosis. The status of the lung microbiome may
85
of healthy Th1 response. be especially important in situations requiring
66
ii. Stress – Stress chemistry is inherently the use of ventilators, as depletion of the lung
inflammatory. 67,68 The immune suppressive effects microbiota by broad-spectrum antibiotics prior to
of cortisol are well known. The challenges related high tidal volume ventilation was shown to render
to using corticosteroids in the COVID-19 context mice more susceptible to developing ventilator-
have recently been reviewed. A recent review induced lung injury. 86
69
examining corticosteroids in COVID-19 suggested vi. Exercise – Physical activity has long been
possible utility in the early acute phase, but known to be critical for proper function of
pointed out that conflicting evidence suggests this virtually all physiological systems. However,
is not conclusive. As mentioned previously, other to decrease inflammation the right intensity is
34
research has suggested that lung inflammation critical with moderate levels effective at lowering
driven by the NLRP3 inflammasome mechanism inflammatory markers while intense exercise
is steroid resistant. Interleukin-1β (IL-1β) does not. IL-6 drives significant inflammatory
12
87
production is driven by NLRP3 inflammasome pathology in COVID-19, as discussed here.
activation, and drives autocrine loop activation Skeletal muscle has been shown to produce and
in macrophages and other cells in which NLRP3 releases significant levels of IL-6 after prolonged
activation is taking place, reinforcing Signal 1 of exercise, so caution should be used when
88
the inflammasome assembly sequence. Non- considering the form and duration of exercise.
23
steroidal treatments targeting inflammasome
activation, specifically the IL-1R antagonist b. Supporting levels of vitamins and minerals with
anakinra, has been shown to block LPS-induced known immunological roles. (see details and
neutrophil influx in healthy subjects. references in Tactics section below)
64
Cortisol and norepinephrine elevation have
also been shown to induce apoptosis of Th1 cells c. Identification of risk factors that represent
and NK cells in TBI and drive Th2 responses in increased risk of the patient entering the Escalating
70
response to inhaler use in asthma. Though the Inflammation Phase, if they were to become
71
experience of having COVID-19 would itself be infected with SARS-CoV-2. Patients in this category
considered a source of acute stress, it should be are likely candidates for NK cell and Th1 cell support
considered that, in many cases, the acute stress is at baseline. (see details and references in Tactics
occurring on top of weeks or months of chronic section below)
stress associated with social isolation and related
factors. Target 2 - Natural Killer (NK) cell support
iii. Glycemic control – Insulin resistance, obesity, NK cells drive the core immunological response to
and impaired glucose tolerance have all been viral infection. The diversity of NK cell types and their
shown to be associated with inflammation. 72-74 roles in the healthy and diseased lung have been reviewed.
89
iv. Dietary factors – Improvements in diet Their overall immunological relevance and coordination
are strongly associated with reductions in with Th1 cells in antiviral immune response are discussed
inflammation. 75-78 in tandem with the Th1 cell discussion below.
v. Microbiome Balance – Both the lung and the GI
tract have a normal microbiome and the complex Target 3 - T Helper Type 1 (Th1) cell support
relationship between the microbiota of the lung Th1 cells play a key role in antiviral immunity.
and GI tract, and its bidirectional influence Th1 cells and NK cells support each other’s activation via
with the immune system, has been reviewed. their loop-reinforcing interactions with macrophages.

Yanuck—Immuno-physiological Approach to COVID-19 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print 13