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Can Vitamin D Positively Impact COVID-19 Risk and Severity Among Older Adults: A Review of the Evidence

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Abstract

Discusses the possible interaction/independent actions of vitamin D and risk of Covid-19 among older adults
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JOURNAL OF AGEING RESEARCH AND HEALTHCARE
ISSN NO: 2474-7785
Research
Can Vitamin D Positively Impact COVID-19 Risk and Severity Among Older Adults: A Review of the
Evidence
Ray Marks1,*
1Department of Health and Behavior Studies, Teachers College, Columbia University, New York, NY 10027, USA
Abstract:
Background: The coronavirus Covid-19 strain that emerged in December 2019, continues to produce a
widespread and seemingly intractable negative impact on health and longevity in all parts of the world,
especially, among older adults, and those with chronic health conditions.
Aim: The first aim of this review article was to examine, summarize, synthesize, and report on the research
base concerning the possible use of vitamin-D supplementation for reducing both Covid-19 risk and severity,
especially among older adults at high risk for Covid-19 infections. A second was to provide directives for
researchers or professionals who work or are likely to work in this realm in the future.
Methods: All English language relevant publications detailing the possible efficacy of vitamin D as an
intervention strategy for minimizing Covid-19 infection risk published in 2020 were systematically sought. Key
words used were:
Vitamin D, Covid-19,
and
Coronavirus
. Databases used were PubMed, Scopus, and Web of
Science. All relevant articles were carefully examined and those meeting the review criteria were carefully read,
and described in narrative form.
Results: Collectively, these data reveal vitamin D is a powerful steroid like compound that is required by the
body to help many life affirming physiological functions, including immune processes, but its deficiency may
seriously impact the health status and well being of the older adult and others. Since vitamin D is not
manufactured by the body directly, ensuring those who are deficient in vitamin D may prove a helpful overall
preventive measure as well as a helpful treatment measure among older adults at high risk for severe Covid-19
disease outcomes.
Conclusions: Older individuals with chronic health conditions, as well as healthy older adults at risk for vitamin
D deficiency are likely to benefit physically as well as mentally, from efforts to foster adequate vitamin D levels.
Geriatric clinicians can expect this form of intervention to reduce infection severity in the presence of Covid-19
infection, regardless of health status, and subject to careful study, researchers can make a highly notable impact
in this regard.
DOI: 10.14302/issn.2474-7785.jarh-20-3650
Corresponding author: Ray Marks, Department of Health and Behavior Studies, Teachers College, Columbia
University, New York, NY 10027, USA, Tel: +1-212-678-3445, Fax: +1-212-678-8259,
Email: rm226@columbia.edu
Keywords: Coronavirus, Covid-19, infection, immunity, older adults; prevention, therapeutic use of vitamin D
Received: Dec 05, 2020 Accepted: Dec 05, 2020 Published: Dec 10, 2020
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Introduction
The COVID-19 or pandemic remains an
intractable problem despite months of study and
investigation of the many possible causes, as well as
strategies for amelioration or prevention. At the same
time, adults with a variety of chronic health conditions
may not be able to either access or receive optimal care
due to many travel and other social restrictions. This
narrative report focuses on vitamin D as a possible
antidote to the widespread risk of severe illness on
acquiring this virus, as well as for mediating its severity,
and fostering a more rapid return to health. Since
vitamin D may prove helpful for ameliorating or
preventing Covid-19, and sunlight is one source of
vitamin D that may be challenging to harness by many
who are home bound or live in northern countries, or
who are bound by a variety of cultural norms, work
situations indoors or underground, or living in regions
where the potency of ultraviolet light is diminished as a
result of global warming, can a case be made for
vitamin D supplementation among older at risk adults
and others? Indeed, older adults, especially those who
now have restrictions placed on their movements due to
the Covid-19 pandemic may not only be highly
vulnerable to the consequences of vitamin D deficiency,
but may not understand the implications of their
situation in this respect, even if they personally follow
legal Covid-19 rulings in all respects.
Discussed is the evidence base in favor of
efforts to ensure all citizens, including older adults, and
especially those with chronic health conditions
associated with a deficiency of vitamin D, such as
diabetes, one of four main disease correlates found
among Covid-19 cases. Some information on the past
use of vitamin D in other infectious diseases such as
influenza is discussed as well.
Drawn largely from the PUBMED database, the
overview should provide the interested reader a general
view of past work as well as current trends in this
regard that might be worthy of further consideration
and study, as well as applications in the health care
field.
Covid-19, which may occur independently as a
separate health condition, or in conjunction with one or
more chronic health conditions, may well be life
threatening, and even if not, may induce the presence
of other illnesses, while heightening prevailing adverse
life events and functional losses, including immense life
quality and socioeconomic losses. While the world waits
for a possible Covid-19 antidote, other remedies to
offset excess risk of Covid-19 and its consequences
must be sought as argued by Simonson [1]. In this
regard, mounting evidence points to a possible role for
vitamin D in explaining infection risk, as well possible
benefits of intervening in this regard to offset or
minimize this risk.
Although research in this realm is clearly in its
infancy, and based largely on observational studies,
Covid-19 infection and death rates do appear to be
notably higher in the elderly than any other sub group,
and this may be mediated in part, by the presence of a
prevailing vitamin D deficiency. Since many adults suffer
from this particular deficiency, it can be argued that a
proportion of Covid-19 cases may be preventable. Since
vitamin D sources are several, potential efforts to attain
adequate sunlight exposure, exposure to foods or
beverages containing vitamin D, and/or supplementation
of vitamin D in vulnerable adults may be more beneficial
than not.
Indeed, if found to be influential in any way,
intervention in this regard may provide one avenue that
is reasonably practical for purposes of securing the well-
being of the aging person, especially in the case of the
chronically ill older adult that alone can heighten risk of
infection due to its overall potentially debilitating effect
on immune, musculoskeletal and cognitive health.
Others may be given medications that render them
more prone to Covid-19, and less likely to be good
surgical candidates or ventilator candidates if they have
severe disabling chronic health conditions, especially
those who may also be vitamin D deficient.
This work is significant because the ability to
minimize Covid-19 risk and severity is currently of the
highest importance, especially among the elderly
confined to their homes in isolation, as well as nursing
homes, or to situations that limit sunlight and nutrient
based vitamin D exposure. As discussed by Mok et
al. [2], the Covid-19 pandemic proceeds unabated,
despite considerable public health efforts to mitigate this
spread. The development of a vaccine is still awaiting
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confirmation, and even then vaccinations may be only
part of the solution. However, other compounds with
antiviral properties may be helpful to consider not only
in the interim, but in the future.
Aims
This narrative review aimed to specifically
examine the value of vitamin D therapy for or
minimizing the risk of acquiring Covid-19 infections in
the older population, especially those with preexisting
vitamin D deficits. Its second aim was to offer
recommendations for future consideration by clinicians
and researchers in the field based on these findings.
Materials and Methods
To obtain the data for this review, the electronic
data sources PUBMED, Scopus, and Web of Science were
searched. The time period searched ranged from January
1 2020- December 2, 2020 and the key words included
Covid-19, vitamin D, coronavirus, older adults
. All forms of
study or analysis were deemed acceptable. However,
because most empirical studies are in process, and
unpublished, and no consistent intervention approach
could be identified among these trials, a narrative
summary of all available data including case studies, and
uncontrolled observational studies was implemented.
Selected material had to focus on vitamin D related facts
relevant to infection risk and recovery, as well as
symptoms of infection in the older adult. Excluded were
articles that did not focus specifically on this set of issues
and non English based articles. Preprints were used to
highlight the possible scope and updated findings
concerning this present topic, rather than for prescribing
clinical guidelines.
Results
Of the more than 60,000 publications on Covid-
19, published as of December 2 2020, a total of 307
articles potentially relevant to the current topic were listed
on PUBMED. Very few additional articles were found on
the additional web sites. In terms of the topic of interest
to this report, however, only 75 articles were deemed
relevant as more publications than not did not meet
criteria for this review, for example, they discussed
vitamin D in children, or were letters to the editor. Even
when the topic of the listed publication was relevant, it
was clear that the prevailing reports were predominantly
literature reviews, rather than actual studies. These were
not uniform however, and tended to discuss studies with
considerable variation in the samples studied, as well as
types of vitamin D and modes of usage, with no
consistency in reviewed content or overall approach. Most
too, focused on the role of vitamin D as deduced from
past studies on acute respiratory infections, or alternately
on currently recorded medical records or observations on
Covid-19 hospitalized cases made on a single occasion,
rather than any observed prospective follow up studies. In
particular, among the available publications related to
Covid-19, and vitamin D the majority do not currently
focus on vitamin D as a possible primary or secondary
prevention approach. Indeed, very few have examined
the possible role of vitamin D as an important biological
determinant in mediating risk and outcomes of Covid-19
as experienced by older adults, even though vitamin D
tends to meet Hills criteria for infection causality as
detailed by Annweiler et al. [3].
To provide an overview of this quite considerable,
but potentially highly relevant material in this regard, this
review chose to discuss the science base and basis as
regards vitamin D as a form of possible form of prevention
and/or therapy relative to acute respiratory infections,
such as Covid-19 among older adults. Findings regarding
its specific immune related benefits and others relevant to
the safely and life quality of the older adult are described.
The term vitamin D is applied throughout, even though
several formulae and categories of this compound exist.
Prior Studies
Past research on the value of vitamin D in the
context of health status, shows this compound in its
various forms has the potential to strongly influence
overall health status and outcomes across the lifespan,
including the elderly, as well as outcomes of infections
analogous to the Covid-19 pandemic. While most of these
data point to research on vitamin D deficits and how these
may raise the risk of more severe infection responses in
the vulnerable adult [1, 4], other data show that there is a
positive benefit of vitamin D supplementation on the risk
of acute respiratory infection, depending on dosage.
Simonson [1] also reports on the possible linkages of
chronic health conditions, as well as Northern latitudes
and cold weather that can implicate vitamin D deficits in
exacerbating Covid-19 morbidity rates. The link between
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vitamin D and the immune system functioning has also
been discussed [4].
Current Reports
Among the 75 studies and reports retrieved from
the present search, Merzon et al. [5] who evaluated the
degree of association between plasma vitamin D levels
and the presence of Covid-19 disease and
hospitalizations among 14,000 members of a Health
Services unit found 10.1% to be Covid-19-positive. They
also noted that the mean plasma vitamin D level among
this infected group was significantly lower than that of
the negative Covid-19 group. While the low vitamin D
level may have been the caused by the Covid-19
presence, their univariate analysis demonstrated an
association between low plasma vitamin D levels and the
increased likelihood of acquiring a Covid-19 infection,
followed by hospitalization due to this virus. In a
multivariate analyses that controlled for demographic
variables as well as psychiatric and somatic disorders,
the adjusted odds of acquiring Covid-19 infections, as
well as hospitalization due to the virus was unchanged,
implying that a low vitamin D status is a possible risk
factor for acquiring or exacerbating Covid-19 infection
risk and severity.
Martineaus et al. [6] who assessed the overall
effect of vitamin D supplementation on risk of acquiring
an acute respiratory tract infection, associated with
Covid-19 by reviewing data from several electronic data
bases up until 2015 that were randomized, double blind,
placebo controlled trials of vitamin D supplementation of
any duration showed vitamin D administration was
beneficial overall. That is, of the 25 eligible randomized
controlled trials housing a total of 11 321 participants up
to 95 years of age, vitamin D supplementation appeared
to reduce the risk of acute respiratory tract infection
among all participants. In subgroup analysis, protective
effects were also seen in those receiving daily or weekly
vitamin D without additional bolus doses. It was
concluded that vitamin D supplementation is able to
safely protect against acute respiratory tract infection
overall, and cases who are vitamin D deficient and
receive non bolus supplements of vitamin D experience
the most benefit.
Mok et al. [2] who examined a natural product
library, among other sources in the search for Covid-19
prophylactic compounds, shortlisted the active form of
vitamin D, termed calcitriol, as a prospective adjunctive
agent in this regard. They then provided well
documented background evidence that vitamin D has
the potential to exhibit significant potent activity against
Covid-19 or SARS-CoV-2. According to this group, their
review findings pave the way for consideration of a
practical host-directed therapy for helping to protect
against SARS-CoV-2 or Covid-19 infection. Their
arguments align to some degree at least with those of
Mendy et al. [7] who sought to identify factors
associated with hospitalization and disease severity in a
racially and ethnically diverse cohort of COVID-19
patients and found that among the 689 Covid-19
patients in their study, a vitamin D deficiency was one
factor associated with hospitalization and/or disease
severity.
As well, Laird et al. [8] who specifically
examined the role of vitamin D in the context of
inflammation similarly support a strong plausible
biological hypothesis and evolving epidemiological data
as regards a favorable role for vitamin D in mitigating
Covid-19 risk as proposed by Melzer et al. [9], especially
in the case of any vitamin D deficiency. This is
important to note, given that according to Zemb et al.
[10] a vitamin D deficiency is easily modifiable, and daily
vitamin D supplementation with moderate doses is safe
and cheap. Moreover, even a small decrease in Covid-19
infections would easily justify this intervention even
though disputed by Hastie et al. [11].
Ali et al. [12] further propose that since vitamin
D is known to mitigate the scope of acquired immunity
and to help regenerate endothelial lining damage, its
thoughtful usage may be especially beneficial in
minimizing the damage that often accompanies damage
to alveolar structures in cases of acute respiratory
diseases. These protective effects appear as well to
increase up to 19% in those individuals subject to daily
or weekly regimens of vitamin D compared to those
dosing on a monthly bolus of vitamin D. Furthermore,
there is a possible 70% chance of an effective protective
outcome when a vitamin D deficiency is corrected by
supplementation according to this group.
Radujkovic et al. [13] who studied 185 patients
diagnosed with Covid-19 as regards vitamin D status at
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first presentation found 50% of these patients required
hospitalization and a total of 22% were vitamin D
deficient. When adjusted for age, gender, and
comorbidities, this deficiency was associated with higher
risk of severe illness and death, highlighting the need
for interventional studies on vitamin D supplementation
in this patient group.
According to Carpagnano et al. [14] who
elected to examine the presence of vitamin D levels in
42 patients with acute respiratory failure due to
Covid-19, 81% had hypovitaminosis D. As well their
survival analysis showed that those patients with a
severe vitamin D deficiency had a 50% chance of dying,
while those with vitamin D levels  ≥ 10 ng/mL had a 5%
chance of dying at 10 days.
Similarly Brenner et al. [15] who assessed the
extent of vitamin D insufficiency and deficiency, and
their association with mortality from respiratory diseases
during 15 years of follow-up among 9548 adults ages
5075 found high rates of vitamin D insufficiency and
deficiency among this cohort. Compared to those with
sufficient vitamin D, these aforementioned participants
had increased respiratory mortality rates, hence,
implying that vitamin D supplementation may be helpful
in efforts to limit the immense burden of the Covid-19
pandemic.
State of Research
As noted above, the reports documented in this
review, which are largely current, stem predominantly
from either hypothetical, analogous research in the
realm of respiratory conditions, anecdotal or
observational data, hence should be viewed with
caution, despite their overall meaningful conclusions in
the face of a pandemic that has produced few
preventive pharmacologic based strategies or
amelioration approaches that are readily accessible and
cost-effective. Indeed, as per Grant et al. [16] several
observational studies and clinical trials do imply that
vitamin D supplementation may be able to reduce the
risk of influenza, even if this is not a consistent finding,
and must thus be of sufficient current import to
examine further [17]. As well, even though support for
this idea may not be universal, the design and basis for
the few available contrary studies has been questioned
[17], thus these data too must be viewed cautiously to
avoid discarding a potentially valuable adjunctive
intervention, when in fact it may be helpful. Additionally,
although several authors recommend that to reduce the
risk of infection, very high vitamin D usage may be
helpful to offset infection rates in vulnerable adults at
risk for Covid-19, excess levels of vitamin D may prove
more harmful than not, and should be studied carefully,
before universally adopting its administration to the
older severely affected adult with a Covid-19 infection.
On the other hand, as proposed by Caccialanza
et al. [19] efforts towards ensuring safe efficacious
vitamin D serum levels and methods of delivery should
be examined carefully to establish if any of these can
help to reduce the risk of respiratory failure requiring
non-invasive ventilation or continuous positive airway
pressure that limits food and beverage intake, and with
this vitamin D analogs. According to Kakodkar et al. [20]
there is also a need for assessing multiple parameters
that influence and could influence the clinical course of
Covid-19 infections and that may require optimization,
as focusing on a single item may not prove efficacious
in the long-term. However, as implied by DAvolio
et al. [21], moreover vitamin D concentrations in the
plasma obtained from a cohort of patients in
Switzerland did suggest vitamin D is one potentially
important adjunct to bear in mind in the context of the
Covid-19 fight’ [22].
As well a careful review of allied past, as well as
several existing studies (sampled in Table1), shows
vitamin D deficits may predispose to infection of the
lungs, and that the multiple mechanisms involved can be
explained by vitamin D presence and extent of
availability [4, 23]. Other data show, older adults who are
affected most by Covid-19 are more likely than not to
be vitamin D deficient, as well as experience the
observed generally worse Covid-19 infection outcomes
than younger patients. To the contrary,
Ohaegbulam [25] found Covid-19 patients who received
a high dose of vitamin D supplementation achieved
more observable levels of vitamin D normalization, as
well as improved clinical recovery rates. How the
presence of lung disease and/or chronic smoke or
pollution exposure can impact lung tissue vitamin D
status and functioning, is not clear though, and
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Authors Sample Study mode Vitamin D Findings
Brenner et al. [15] 9458 ARD cases Prospective 15 yrs Potentially protective
Baktash et al. [56] Older Covid-19 cases Prospective May predict outcomes
Carpagnano et al. [14] 42 ARD cases Retrospective May predict mortality
Castillo et al. [73] 76 hospitalized cases Pilot randomized trial Reduced Covid severity
DAvolio et al. [21 Swiss patients Retrospective Correlates with Covid-19
Daneshkhah et al. [61] Covid-19 patients Prospective May predict severity
Merzon et al. [5] Members health grp Observational Covid-19 risk factor
Hastie et al. [11] Biobank cases Retrospective No Covid relationship
Ilie et al. [54] Published literature Analytic Suggests Covid-19 link
Kaufmann et al. [27] National lab data Observational Is Covid-19 related
Karahan et al. [65] 149 Covid-19 patients Retrospective Vitamin D/severity linked
Maghbooli et al. [28] 235 Covid cases Observational May impact Covid-19
Mardani et al. [29] 65 male, 58 females Prospective May impact Covid-19
Munshi et al. [30] 7 studies Analytic May be linked to Covid
Ohaegbulam et al. [25] 4 cases low vitamin D Case series Supplements help
Panagiotou et al. [31] Cohort ill patients Retrospective Severe Covid linkage
Pizzini et al. [32] 109 cases at 8 wks Prospective Low vitamin D-no effect
Radujkovic et al.[13] 185 Covid-19 cases Prospective Impacts Covid outcome
Sabetta et al. [33] Healthy subjects Prospective cohort Lowers ARD risk
Table 1. Summary key study findings as of December 2, 2020 regarding the possible importance of efforts to
identify vitamin D deficient older adults in the context of primary, secondary, and tertiary Covid-19 prevention
approaches
Abbreviations: ARD: Acute respiratory disease; Covid: Covid-19; grp: group; wks; weeks
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warrants examination [26].
Discussion
Although modern medicine has previously been
quite successful in managing infection rates globally,
despite periodic epidemics, it is less successful in
arresting rates of Covid-19 infections globally. While the
world awaits an effective vaccine, as per Ebadi and
Montano-Loza [24] it appears plausible however, to
make a case for the possible use of vitamin D
supplements in influencing the incidence and severity of
the infection at the early stages of the disease, due to
its protective immune response potential for eliminating
the virus [39]. As the disease progresses, lung
inflammation and fibrosis due to the release of pro-
inflammatory cytokines may also be found to decrease,
and if used appropriately, in line with its past
importance in reducing the impact of respiratory virus
processes [3], vitamin D may also slow the disease
progression or even improve patient survival [3].
Moreover, cumulative evidence points not only
to the impact of vitamin D on many genes with a well-
established salience to airway infections, as well as
immune processes [45], but to the additional fact that a
low vitamin D status could potentially be important in
explaining the mechanistic link between age,
comorbidities and increased susceptibility to
complications and mortality due to Covid-19 at least in
some countries [46]. In countries such as Italy
where vitamin D is predominantly prescribed to
post-menopausal women with osteoporosis, it is possible
older men are, at least in part, more vulnerable to the
most serious consequences of the infection on this
basis [46]. At the same time, vitamin D deficiency or
insufficiency has been shown to be both a risk factor for
acquiring Covid-19, but also for its severity [3], while
multiple benefits of vitamin D have been reported that
would be useful for Covid-19 risk reduction and
intervention as shown in Box 1. Thus, given the
magnitude of the public health problems caused by
Covid-19 in an aging population, and no sound solution,
it appears more research to confirm the potential for
vitamin D to minimize the risk of infection, and its
severity will most certainly prove advantageous. In
addition to those gaps identified here through the
literature search, needed in particular, as well as urgently,
are well designed adequately powered comparative
studies of vitamin D similar dosages, dosage strategies,
disease stages, and cohorts with varying age ranges and
health status, as well as population-based prophylactic
trials [3, 42].
At the same time, as outlined by Grant et
al. [16], it is clear that the world remains in the grip of
the Covid-19 pandemic, and that it does not seem
intuitive to await the outcomes of these trials in the
event the adult at risk clearly has a prevailing vitamin D
deficit. Provided under the care of physicians, there
appears to be sufficient evidence to implement such a
personal as well as possible public health measure that
can in all likelihood reduce infection risk and magnitude
in the older adult, over and above isolation, distancing
and masking, in a safe manner. Those who are obese,
those who are food insecure, and those of Black or
Asian origin may need to be preferentially targeted.
Indeed, Ali and colleagues [12] who examined the role
of vitamin D in preventing of Covid-19 infection,
progression and severity concluded that despite the
weak evidence base, people at higher risk of vitamin D
deficiency during this global pandemic should consider
taking safe levels of vitamin D supplements or food
based sources to maintain the desired levels of
circulating vitamin D. The observation of a quadratic
relationship between the prevalence of vitamin D
deficiency in most commonly affected countries by
Covid-19 and the latitudes [47], plus possible additional
health benefits of vitamin D supplementation alone in
deficient older cases appears to be an added reason for
considering this idea. As well, such improvements, as
well as less severe Covid-19 disease are likely to
significantly outweigh the risks of failing to do
this. [48-50].
On the other hand, knowing that high doses
may pose a risk to an older adult, avoiding these excess
doses pending further study seems wise as discussed by
Lanham-New et al. [49] and Bliezgys et al. [46]. Indeed,
why the dosages discussed among the key strategies
being studied in currently registered vitamin D Covid-19
trials have been selected warrants more definitive
clarification [34], as collectively, they do not appear to
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follow what works in other acute respiratory
infections [42], nor are the majority uniform in delivery
approaches or in compliance with daily recommended
dosages to achieve and maintain optimal serum vitamin
D levels. In addition, some of these trials assess
multiple treatment approaches simultaneously, use
unspecified vitamin D doses [NCT04449718], differing
samples, time periods of study, plus outcome measures.
Despite the urgency of one or more of these efforts,
many however, have not begun recruitment, and those
that have may only have results in more than a year
from present time. Thus, how these diverse data sets,
will inform practice either presently or in the future is
unclear, especially if therapeutic doses tested do not
concur with daily recommended doses in any
comparable way. The ethics of studying high versus
standard dose supplements of vitamin D in Covid-19
patients [NCT04344041], as well as the use of placebo
interventions, must also be questioned. Finally, is it
ethical to withhold a reasonably well established
supplement from high risk older populations, who have
high Covid-19 susceptibility, high mortality rates, along
with predictable vitamin D deficits, when the need is so
acute? Even if older adults have adequate vitamin D
levels when admitted to hospital, they may surely suffer
vitamin D deficits attributable to inflammatory
respiratory disease dysregulation factors [42] that may
delay their recovery if not addressed. As of October
2020, although there are 54 possible related trials cited
at the Clinical.Trials. gov website, only 2 are completed
with no results; 2 have results, but are not directly
related to the determination of vitamin D efficacy in a
Covid-19 context. One is a clinical trial of Ivermectin
plus Doxycycline for the treating confirmed Covid-19
infections, the other examined whether
Hydroxychloroquine is effective in reducing Covid-19
progression.
One of 22 cited studies and listed as actively
recruitingpatients, proposes to test the efficacy of
either daily high dose vitamin D supplementation (6000
IU vitamin D3/day) versus standard care. Those
individuals ≥50 years of age or older who test positive
for COVID-19 at baseline will be randomized to
bolus vitamin D (20,000 IU/day for 3 days) followed by
high dose (6000 IU vitamin D/day) vs. standard of care
for 12 months. All participants will receive a
multivitamin containing vitamin D-but the rationale for
these doses and mode of application do not seem to
parallel the daily recommended doses for an older
population, such as that being studied, and may be
detrimental and are not recommended [51]. Even if
advocated [16], these high doses seem impractical for
purposes of fostering population wide health protection.
There are only 140 cases being recruiting and
completion is set for the end of 2021. This study also
administers a placebo across the study time period-even
though this may lower the overall health benefits that
would be attained by applying the actual compound.
Since all subjects are given a multivitamin with vitamin
D, the precise benefits of vitamin D supplementation
per se may not be discernible. Some of the studies
presently recruiting subjects also examine other dietary
sources, unspecified vitamin D doses, various
pharmaceutical products, vitamin C, vitamin D as a
prognostic marker, or apply varying vitamin D doses
and modes of delivery to small samples across varying
time periods, and often across multiple test sites.
Moreover, samples vary in health status, ages studied,
sample sizes, and primary and secondary outcomes
assessed vary widely, and most proposed measurement
approaches do not directly speak to issues of validity,
blinding, subjectivity, and sensitivity, among other
factors. For more data, the papers by Shakoor et
al. [34] and Chakhtoura et al. [52] are relevant, as is
the website of registered trials located at: https://
clinicaltrials.gov/ct2/results?
cond=COVID&term=vitamin+d&cntry=&state=&city=&
dist=
In short, it appears low vitamin D levels, may
adversely impact innate and adaptive immunity that can
lead to Covid-19 infections and their severity and
mortality [65], in part, through the activation of its
antimicrobial peptides that are secreted at mucosal
surfaces, among other different and interactive
mechanisms [See Figure 1 and Box 1].
However, to validate these ideas, as well as to
solidify the data, and overcome conjecture, well-powered
and carefully conceived clinical, as well as epidemiological
and environmental research should be
conducted [35, 47, 50-52, 55, 70-75].
Freely Available Online
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T regulatory lymphocytes can be increased or modulated by vitamin D [1, 34, 62]
May help to reduce cytokine storm severity[1, 61, 62, 66]
May reduce thrombocytic episodes and have a significant anticoagulation effect [1, 35]
Has potential antiviral properties [36]
May limit the expression of anti-oxidant genes [34]
May potentially prevent or mitigate the complications associated with acute respiratory infections [37]
Suppresses the actions of the renin-angiotensin system, which has a determining role in inducing inflam-
matory response related to Covid-19 [38]
May help induce antimicrobial peptides, such as cathelicidine [24, 39, 40, 66]
May help to induce innate immune responses or act as an immunosuppressant [39, 40, 62]
May prevent exaggerated inflammatory responses and further damage to mucosal lung tissue in cases of
virus-induced inflammation [26, 39]
May protect against acute respiratory infections [42, 53] by helping to maintain the integrity of lung based
epithelial tight junctions [34]
May positively impact macrophage modulation and mucus secretion [34, 62]
May help to prevent getting infected or ward off the infection without mortality [62]
May reduce disease severity and need for intensive care [73]
Box I. Specific examples of how vitamin D supplementation may hypothetically promote immunity or more
favourable Covid-19 outcomes among older adults who are vitamin D deficient or at risk for deficiency via its
multiple gene regulating abilities [5]
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Future Research Directions
Areas that could be fruitful to focus on in the
future are:
The correlates of prevailing health status,
prescription medication usage, and/or cultural
practices that may preclude adequate sunlight
exposure.
Air pollution and this possible Covid-19
correlate [31, 51, 53].
Other topics that might prove fruitful if
examined more intently are Covid-19 associated
inflammation, coagulopathy, reduced platelet count, and
prolonged prothrombin time and other outcome
correlates [24, 68].
Moreover, since the vitamin D dosages that
would possibly prove impactful among various older
adults at risk for Covid-19 are not well established at all,
more attention to this issue appears necessary. At the
same time, greater efforts towards controlling for
current medication and supplement usage, as well as
sunlight in forthcoming studies is essential.
In addition, a sizeable number of scholars point
to the value of specifically examining the potentially
influential role of gender, geography, health status,
living arrangements, nutrient intake and access on
intrinsic vitamin D availability levels and need in efforts
to heighten immune function and reduce Covid-19 risk
and fatalities [31, 52, 59, 63, 64, 69, 70-75].
Conclusion
Covid-19 infections clearly remain immensely
problematic to control and treat, especially among older
adults, but could be impacted favourably by vitamin D
supplements and intake, as indicated.
Ascertaining whether this may help seems
imperative even if a vaccine is forthcoming.
Acknowledgements
None
Figure 1. Possible Pathways of Covid-19 Infections: *-showing mechanisms where vitamin D may be
helpful
[Adapted from; 1, 28, 34, 39, 62, 63, 65, 71-75]
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Conflicts of Interest
None
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Background It is clear that in UK healthcare workers, COVID-19 infections and deaths were more likely to be in staff who were of BAME origin. This has led to much speculation about the role of vitamin D in healthcare worker COVID-19 infections. We aimed to determine the prevalence of vitamin D deficiency in NHS staff who have isolated with symptoms suggestive of COVID-19 and relate this to vitamin D status. Methods We recruited NHS healthcare workers between 12 th to 22 nd May 2020 as part of the COVID-19 convalescent immunity study (COCO). We measured anti-SARS-Cov-2 antibodies using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was determined by measurement of serum 25(OH)D 3 using the AB SCIEX Triple Quad 4500 mass spectrometry system. Findings Of the 392 NHS healthcare workers, 214 (55%) had seroconverted for COVID-19. A total of 61 (15.6%) members of staff were vitamin D deficient (<30 nmol/l) with significantly more staff from BAME backgrounds or in a junior doctor role being deficient. Vitamin D levels were lower in those who were younger, had a higher BMI (>30 kg/m ² ), and were male. Multivariate analysis revealed that BAME and COVID-19 seroconversion were independent predictors of vitamin D deficiency. Staff who were vitamin D deficient were more likely to self-report symptoms of body aches and pains but importantly not the respiratory symptoms of cough and breathlessness. Vitamin D levels were lower in those COVID-19 positive staff who reported fever, but this did not reach statistical significance. Within the whole cohort there was an increase in seroconversion in staff with vitamin D deficiency compared to those without vitamin D deficiency (n=44/61, 72% vs n=170/331, 51%; p=0·003); this was particularly marked in the proportion of BAME males who were vitamin D deficient compared to non-vitamin D deficient BAME males (n=17/18, 94% vs n=12/23, 52%; p=0·005). Multivariate analysis revealed that vitamin D deficiency was an independent risk factor for seroconversion (OR 2·6, 95%CI 1·41–4·80; p=0·002). Interpretation In those healthcare workers who have isolated due to symptoms of COVID-19, those of BAME ethnicity are at the highest risk of vitamin D deficiency. Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff. Funding This study was funded internally by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust and supported by the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. AAF and DRT are funded by the Medical Research Council (MR/S002782/1). The Binding Site (Edgbaston, UK) have provided reagents and plates for the SARS-CoV-2 ELISA free of charge. Research in context Evidence before this study The ongoing COVID-19 pandemic has raised several questions, one of which is whether individuals with vitamin D deficiency were at a greater risk of being infected or having a severe outcome if infected. Among UK healthcare workers, and indeed the general population, individuals of BAME ethnicity are disproportionately affected by COVID-19. It is well established that individuals of BAME ethnicity have a higher prevalence of vitamin D deficiency, but it is unknown if vitamin D deficiency among UK NHS workers was connected to the risk of COVID-19 infection. Our search of the literature revealed no previous studies have established the prevalence of vitamin D deficiency within a UK NHS trust. Unsurprisingly, there is also no evidence to suggest if vitamin D deficiency was connected to the risk of infection among UK healthcare workers. Added value of this study In this study of healthcare workers who had isolated for COVID-19 symptoms towards the end of UK surge within a large UK NHS trust, 15.6% were vitamin D deficient. Our data also reveal that healthcare workers of BAME ethnicity and those who had seroconverted for COVID-19 were more likely to be vitamin D deficient. Multivariate analysis also show that vitamin D deficiency was the only predictor of COVID-19 seroconversion. Vitamin D deficient healthcare workers that are BAME and male had a 94% seroconversion for COVID-19 compared to non-deficient BAME males suggesting they are more at risk of COVID-19 if vitamin D deficient. Implications of all the available evidence There is an increased risk of COVID-19 infection in healthcare workers with vitamin D deficiency. Our data adds to the emerging evidence from studies in the UK and across the globe that individuals with severe COVID-19 are more vitamin D deficient than those with mild disease. Finally, ours and the available evidence demonstrate vitamin D supplementation in individuals at risk of vitamin D deficiency or shown to be deficient may help alleviate the impact of COVID-19.
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Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.
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There is still limited evidence regarding the influence of vitamin D in people with COVID-19. In this systematic review and meta-analysis, we analyze the association between vitamin D deficiency and COVID-19 severity, via an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. Five online databases-Embase, PubMed, Scopus, Web of Science, ScienceDirect and pre-print Medrevix were searched. The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19. The main outcome was the prevalence of vitamin D deficiency in severe cases of COVID-19. We carried out a meta-analysis with random effect measures. We identified 1542 articles and selected 27. Vitamin D deficiency was not associated with a higher chance of infection by COVID-19 (OR = 1.35; 95%CI = 0.80-1.88), but we identified that severe cases of COVID-19 present 64% (OR = 1.64; 95%CI = 1.30-2.09) more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization (OR = 1.81, 95%CI = 1.41-2.21) and mortality from COVID-19 (OR = 1.82, 95%CI = 1.06-2.58). We observed a positive association between vitamin D deficiency and the severity of the disease.
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In December 2019, a new infectious complication called CoronaVirus Infectious Disease-19, briefly COVID-19, caused by SARS-COV-2, is identified in Wuhan, China. It spread all over the world and became a pandemic. In many individuals who had suffered SARS-COV-2 infection, cytokine storm starts through cytokine overproduction and leads to Acute Respiratory Syndrome (ARS), organ failure, and death. According to the obtained evidence, Vitamin D (VitD) enhances the ACE2/Ang(1–7)/MasR pathway activity, and it also reduces cytokine storms and the ARS risk. Therefore, VitD intake may be beneficial for patients with SARS-COV-2 infection exposed to cytokine storm but do not suffer hypotension. In the present review, we have explained the effects of VitD on the renin-angiotensin system (RAS) function and angiotensin-converting enzyme2 (ACE2) expression. Furthermore, we have reviewed the biochemical and immunological effects of VitD on immune function in the underlying diseases and its role in the COVID-19 pandemic.
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Background & Aims: The covid19 is a world changing challenge. Furthermore, this disease challenges our capacities to change our point of view in the domain of infectiology, immunology and global public health. Many trials try some drug such as antiviral (lopinavir, remdesivir) interferon, and the chloroquine. Unfortunately, all approach is not really convincing at this time. We are proposing another approach on this issue. In infectiology there are two protagonists : the host and its immune system versus pathogens and its virulence. Our approach focuses on an intervention on the host’s immune system and how stimulate and modulate its reactions. Methods: We searched on PubMed and Google Scholar databases for French and English-language studies, without a limit of date of publications, for randomized clinical trials, meta-analyses, reviews, systematic reviews, observational studies, case report. We performed a review on the field of immunology enhancements by nutrients use. Results: We identified groups of vitamins (D and C), oligo-elements (magnesium, zinc, selenium) and nutrition advice which enhance immune system response. Indeed, these supplements have some proved properties in modulating and stimulating the immune system. For example, a recent study demonstrates that vitamin D deficiency is linked with the severity of covid19. Majority of the population has a deficiency in these elements. According to this, we propose a therapeutic protocol using these elements to reach an efficient therapy against covid19 by enhancing host’s immune system. Conclusion: Due to this serious pandemic, any solutions must not be disregarded. The nutrition way is an entire part of the solution.
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The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk of or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.
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Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P < .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.
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Vitamin D (VitD) deficiency is considered a global problem and might be associated with higher risk to get COVID-19 illness. In the light of COVID-19 pandemic, VitD might be a promising agent for fighting the SARS-CoV-2, since VitD is involved in various pathophysiological mechanisms that occur during COVID-19 infection. High-dose VitD supplementation, particularly for risk groups, could be recommended to achieve and maintain optimal (range 40-60 ng/ml) serum 25-hydroxy vitamin D levels (marker of VitD status) both for COVID-19 prevention and treatment.