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Vitamin A, especially when in balance with Anosmia (loss of smell) and dysgeusia (distorted
vitamin D, has low toxicity except at high dosages. For sense of taste) are commonly being reported in
adults, toxicity is typically seen after 100 000 IU/d for patients at every phase of COVID-19. These are
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6 months. A study that looked at the positive effects also classic symptoms of zinc deficiency. It is too
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of multivitamin supplementation in women with HIV early in the discovery process to determine if this is
showed that Vitamin A was detrimental to outcome. cause or effect, nonetheless zinc deficiency greatly
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However, in this study, vitamin A was supplemented impairs immune function, especially resistance to
in the absence of the other fat soluble vitamins viral infections. Notably, inadequate dietary
notably D and K. Animal studies have demonstrated consumption of zinc is found in almost half the
that vitamin A both decreases the toxicity of and older population. 224
increases the dietary need for vitamin D and vice
versa. In addition, concomitant supplementation iv. Vitamin C - Vitamin C is recognized as an essential
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with vitamin D significantly increased the dose of nutrient in many aspects of the immune system,
vitamin A that causes toxicity. especially immune cell function of both the innate and
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Multiple studies have shown that vitamin A adaptive immune responses. 225,226 Microbial killing
deficiency increases inflammation and more limited requires vitamin C for chemotaxis, phagocytosis and
research has shown supplementation decreases generation of ROS. 227,228 Vitamin C deficiency
inflammation. This appears particularly important contributes to decreased immune responsiveness and
for the mucosal barriers. However, the research is increased susceptibility to infections. Once infected,
complex as inflammation itself appears to decrease the enhanced inflammation and metabolic
blood levels of vitamin A. requirements place a further demand for additional
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vitamin C. Vitamin C supplementation has been
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iii. Zinc - Zinc plays a crucial role in the function of shown to both prevent and treat respiratory and
essentially all immune cells. Deficiency of this critical systemic infections. The utility of vitamin C and
element has a profound impact on immune response, thiamine in sepsis has been reviewed. 230
increasing susceptibility to a variety of infections. 208-212 Optimal cell and tissue levels of vitamin C in the
One of zinc’s critical roles in immune function is its plasma saturation range are needed for prophylaxis,
role in thymulin production and activity. 213 while treatment of infections requires significantly
In addition, zinc has specific and well-known higher doses. 231,232 In addition, vitamin C’s role as an
antiviral properties. Increasing intracellular zinc antioxidant is important in protecting the body
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concentrations in cell culture impairs the replication against the damage from oxidative stress generated
of a variety of RNA viruses including SARS-CoV-1. during an infection. 233,234 Vitamin C also plays an
Intracellular zinc has been shown to inhibit RNA critical role in endothelial stability, supporting nitric
synthesis by suppressing the SARS-CoV-1 replication oxide generation and vasodilation. In light of the
and transcription complex. In vivo evidence for coagulopathy found in many COVID-19 patients, this
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zinc’s antiviral role comes from a Cochrane review role seems highly relevant. 235
that found zinc intake was associated with a significant The CITRIS-ALI study, an RCT published in
reduction in the duration of the common cold. Many JAMA in 2019, showed a possible decrease in mortality
of the studies showing benefit when taken during the in 167 patients with sepsis-related ARDS receiving
course of an infection were in the form of a zinc ~15 grams/day of IV vitamin C for four days.
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lozenge. It makes sense to utilize this mode of Recruitment is underway at this writing for an RTC
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delivery during the acute infection phase. IV vitamin C trial (24g/day) in COVID-19 patients
Zinc has also been shown to suppress Th17 cell hospitalized with severe pneumonia. At Northwell
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development. Interleukin-17 (IL-17) made by Hospital in New York, there are multiple anecdotal
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Th17 cells has been shown to drive an inflammatory reports of the use of IV vitamin C (1500 mg TID to
feedback loop via IL-6 induction. Zinc dependent QID) in COVID-19 patients. Those receiving the IV
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transcription factors are involved in the regulation vitamin C appear to be doing significantly better than
of the gene expression of IL-6 and TNFα. The those not receiving it. 238
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effect of SNPs in genes encoding zinc transporters A meta-analysis of six controlled trials published
on blood zinc levels in humans has been examined. in March 2019 demonstrated that an average oral
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Older individuals with gain of function IL-6 SNPs delivery of 2 grams of vitamin C per day shortened
have been shown to have a greater need for zinc. length of ICU stay by 8.9%. In three trials in which
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Zinc supplement in older individuals with gain of patients required mechanical ventilation for over
function IL-6 SNPs and low zinc were shown to have 24 hours, vitamin C shortened the duration by
lower IL-6 and MCP-1 levels upon zinc 18.2%. 239
supplementation.
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20 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print Yanuck—Immuno-physiological Approach to COVID-19