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A randomized, controlled study of IV NAC Dual Role Substances
(50 mg/kg/day for three days) for 27 ICU patients with In considering potential choices for influencing patient
ALI/ARD demonstrated statistically significant immunological function, it is generally useful to consider
improvement in oxygenation and decreased mortality. 378 favoring strategies that support both the goal of efficient
Normally, nebulized GSH would be recommended immune surveillance and also the goal of quieting excessive
for respiratory inflammation. However, the high level of inflammatory activation. These may offer the advantage of
mucous secretion in COVID-19 could impair its ability to efficient anti-pathogenic immunological activity, while also
penetrate deeply enough into the lungs. Therefore, the providing anti-inflammatory functions, so that
authors recommend IV GSH, to protect both the lungs inflammatory cytokine upregulation that comes with
and also the heart from the damaging inflammation. immune response to the virus does not move the patient
While there are a considerable number of controlled high enough on the vertical axis of Figure 4 to increase their
clinical studies on the various forms of NAC, there is a risk of expressing cytokine storm, sepsis, ARDS or other
surprising dearth of such studies on IV GSH as an potential morbidity or mortality. For example, vitamin D
independent therapy. Virtually all existing studies examine inhibits activation of the inflammatory protein complex
the use of IV GSH in conjunction with drugs, especially NFkB. Vitamin D is also necessary for the formation of
383
chemotherapy agents. There are several studies showing macrophage lysosomal enzymes, without which the
modest benefit in Parkinson’s disease, but virtually no macrophages can’t kill phagocytized pathogens.
196
other conditions we could find in PubMed. 379 Because many patients with COVID-19 die of
The research is clear that inhaled GSH substantially complications driven by excessively intense upregulation of
increases blood levels. A few controlled studies have shown inflammatory mechanisms, it is essential to consider that
modest benefit from inhaled GSH in cystic fibrosis and any tactic deployed solely to create an inflammatory
asthma. 380,381 adjuvant may carry with it a greater risk than tactics that
function in the dual roles of supporting anti-pathogenic
Dosage Information efficiency and downregulation of inflammatory response.
Other than research to date cited here, clinical research Further discernment is useful between substances whose
on nutritional substances in COVID-19 has not yet been anti-pathogenic activation is primarily a consequence of
done. All nutritional supports listed here have shown upregulation of inherently inflammatory mechanisms, via
efficacy in human trials in other conditions. Dosages upregulation of NFkB and cytokines like TNFα, IL-1β, IL-6,
recommended here reflect the well over 100 years of and IL-8, versus substances whose anti-pathogenic activity
combined clinical experience and judgement of the authors. relies on upregulation of immune-directing cytokines like
IL-12 and IFNγ, with the consequences of activation
Regarding Pregnancy and the five Targets of Support yielding efficiencies reviewed elsewhere in this paper.
Safety and dosing recommendations of the compounds
listed in the Five Targets of Support have not been Substances Normal to the Body
established for pregnant women. While some, but not all, In the overall clinical endeavor, it is likely useful to
of the recommendations in the foundational Target and consider favoring the clinical application of substances
other Target areas may be safe during pregnancy that are normal to the body, such as GSH, NAC, vitamins
(e.g. vitamin D, zinc, vitamin C, fish oil), appropriate D, A, and C, and zinc.
doses of those nutrients should be determined on an
individual basis by the patient’s care provider. 382
Summary
Data Collection Resources Though much is yet to be understood about the
As clinical experience and research on COVID-19 SARS-CoV-2 virus and COVID-19, substantial knowledge
continue to emerge, more information will become of the underlying immunology and clinical tools that
available to inform clinical decisions about dose and form apply to therapeutic targets in the underlying immunology
of vitamins, minerals, botanicals, and other substances. provide a basis for clinical application, careful observation,
Helpful resources for data collection include the following: and discernment of the needs of patients who seek support
for favorable outcomes in the context of COVID-19. A
1. The Helfgott Institute IRB-approved online case phased functional approach, based on attention to the
registry, available to all clinicians: https://redcap. time course of the disease process, may provide a useful
nunm.edu/redcap/surveys/?s=PE3EHAYDT3 basis for engaging the clinical process with these patients.
Traditional, Complementary and Integrative Health
and Medicine COVID-19 Support Registry
2. https://www.millihealth.com/covid-data
3. The COVID-19 Universal Registry, Cure-19, is a
public dataset registry. https://www.cure19.org/

Yanuck—Immuno-physiological Approach to COVID-19 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print 25