ICU resources for COVID-19, vitamin D and the immune system
Marik Protocol; Front
Line COVID-19 Critical Care Working Group Protocol; Farid Jalali's
beautiful detective work hypothesising about exactly what is happening
in the lungs of COVID-19 patients; Vitamin D to stabilize the
endothelium . . .
Robin Whittle firstname.lastname@example.org
. 2020-04-09 Last update 2020-06-22 15:20 UTC
The updates/ page lists all the significant updates to these cv19 pages.
To the main COVID-19 page of this site: http://aminotheory.com/cv19/
, concerning nutritional supplements - especially vitamin D and boron -
for all adults and some children ASAP, to reduce or eliminate the
tendency for their immune system to be weak and/or dysregulated
(overly-aggressive, pro-inflammatory and so self-destructive) - which
is what causes severe symptoms with COVID-19. There you
will find multiple articles recommending that everyone should have at
least 40ng/ml (100nmol/l) 25OHD levels - and this starts with expectant
mothers and their newborns.
If everyone in the
world was already replete in vitamin D alone (with the current very
poor boron status) then I believe that far fewer people would be dying
or seriously harmed due to COVID-19. In the absence
of proper vitamin D levels, it is possible that boron repletion (such
as 6mg a day, instead of the usual 1mg or so) would be helpful
too. See the main page for more on boron and immunity.
Obesity ../obesity/ would still be a problem, as would some particular patterns of genes ../#haplotypes
- but the outcomes would be far less extreme than they are now, with
many or most of these people seriously deficient in vitamin D and
probably other nutrients. Please see the ../obesity/
for links to research concerning excess adipocytes expressing ACE2, releasing pro-inflammatory cytokines and existing as ectopic adipocytes in the cells of the alveoli.
Be sure to read the Disclaimer!
COVID-19 patients need vitamin D to ensure Th1 lymphocytes in their lungs shut down and so reduce inflammation
This is highly significant:
Th (T helper lymphocytes AKA CD4+
cells which enter the Th1 program of development play an important role
in fighting viral infection and then, ideally, in reducing
25 researchers from the USA, the UK, Chile and New Zealand conducted
ex-vivo research on fluids and blood samples from COVID-19 patients
with severe symptoms, including analysing the behaviour of Th1 cells,
the genes which are activated inside them and how this changes with
vitamin D (25OHD) levels.
The Th1 cells produce IL-6
which is generally a pro-inflammatory cytokine and is found at
dangerously high levels in many conditions, including COVID-19 severe
symptoms, sepsis, ARDS etc. The researchers show that there is an
important autocrine (signaling within the cell W
) pathway which is not operating as it should in these COVID-19 patients.
This pathway involves IL-6 stimulating the production of the anti-inflammatory cytokine IL-10
, as part of the cell ending its Th1 program.
The researchers show that this pathway is completely dependent on 25OHD
levels, since the signaling involves the upregulation of genes for both
the vitamin D receptor VDR and for the CYP27B1 enzyme which converts,
inside the cell, 25OHD into 1-25OHD, the form of vitamin D which
activates the receptor. Once activated, the 1-25OHD-VDR
complex migrates to the nucleus and alters gene expression,
upregulating numerous genes and downregulating others.
Without sufficient 25OHD (from the blood and so interstitial fluid)
these Th1 cells remain stuck in their aggressive phase of operation, in
part by producing the pro-inflammatory cytokine IL-17
With sufficient vitamin D, the cells stop producing IL-17
and produce IL-10
With sufficient vitamin D, in these conditions, with the autocrine
pathway operating as it should. the set of genes which are upregulated
share a significant number of genes with the geneset upregulated by
anti-inflammatory steroids, such as the dexamethasone.
The researchers use the term "VitD-depressed geneset" to refer to the
set of genes downregulated by the successful operation of this
pathway. When comparing the activation of genes in Th1 cells from
COVID-19 patients with severe symptoms, to those from healthy controls:
The VitD-repressed geneset was within the top 1% of all genesets at distinguishing patient from healthy Th cells . . .
This means that in healthy cells, this autocrine pathway was working
correctly - presumably due to the presence of adequate 25OHD and
no-doubt other conditions - while in these COVID-19 patients, it was
not operating, despite the Th1 cells producing plenty of IL-6 and the
presence of other factors which should activate this
pathway. The implication is that the IL-6 cells in the
patients were unhealthy due to lack of vitamin D, since by supplying
25OHD in the lab, this autocrine pathway started operating correctly
a cortico-steroid drug, has recently been shown to reduce mortality
from severe COVID-19, presumably through immunosuppression. A
significant number of the genes that were modulated by VitD were shared
by cortico-steroids. Steroids, including dexamethasone, enhance the
effects of VitD by increasing transcription of VDR. These
data suggest that, in patients with severe COVID-19, addition of VitD
to other immunomodulatory agents might be beneficial. From experience in other diseases, it is unlikely that VitD will be effective as monotherapy. Combination therapy (at lower doses)
could ameliorate the significant adverse effects of high dose steroid
treatments, including over-immunosuppression or metabolic side-effects.
In summary, we have shown that complement [W]
initiates Th1 shutdown via orchestrating an autocrine/paracrine
autoregulatory VitD loop. VitD causes epigenetic re-modeling, induces
and recruits a set of transcription factors including STAT3, c-JUN and
BACH2, that collectively repress Th1 and Th17 programs and induces IL-10 via IL-6 - STAT3 signaling. We show that this
program is down-regulated in the lungs of patients with severe COVID-19
and could be potentially exploited therapeutically by using adjunct
VitD treatment in patients with COVID-19.
Also, it is obvious to me and not stated in the article, if people already
had sufficient vitamin D levels - 40ng/ml or more - then their immune
system response to the virus may well prevent it infecting the lungs,
and if the virus did replicate there, the resultant immune response
would be properly regulated, and not the overly-aggressive,
hyperinflammatory, self-destructive response which is always found in
(and so arguably causes) severe symptoms in COVID-19. The same
surely applies for sepsis, ARDS etc. all of which only tend to happen
to people with very low vitamin D levels.
See the main page ../
for research on COVID-19 severe
symptoms being associated with, and so presumably at least partly
caused by, low vitamin D levels.
Farid Jalali's hypothesis of vascular damage and shunting via diffuse pulmonary-bronchial anastomoses
Be sure to read this beautiful
detective work which offers the best explanation yet for many
perplexing aspects of COVID-19. The first link is to a video
podcast with PDF and discussion and the second is to a text and graphic
presentation with comments by Cameron Kyle-Sidell MD:
Cameron Kyle-Sidell's appreciative comments begin with:
I applaud Dr. Jalali for proposing a model for COVID-19 injury based on
seemingly sound physiologic principles. This model does provide
explanations for anecdotal observations made by bedside physicians
treating COVID-19 patients. For example, the presence of
dorsal-predominant shunting would explain why proning leads to marked
oxygenation improvement that is not sustained once the patient returns
to the supine position.
This work highlights the importance of protecting the integrity of the endothelium and limiting vasoconstriction
, which is caused by excessive angiotensin II, resulting from SARS-CoV-2 destroying the ACE2 receptors. See #2020-Kim
below regarding how important vitamin D 1,25OHD
is for protecting endothelial cells and inducing vasodilation
This is not necessarily just 1,25OHD in the plasma in general, but
could be released in a paracrine fashion (short distance signaling
between nearby cells [W
]) after it is produced internally (in part for autocrine [W
] signaling) and then diffuses out of the cell. Autocrine cell signaling (Khan Academy explanation
is a big part of how immune cells control gene expression, and with
leakage of the internally produced 1,24OHD, we have the possibility of
paracrine reception of this on membrane-bound vitamin D receptors of
nearby cells, such as the endothelial cells described by #2020-Kim
, where it would upregulate endothelial protection and nitric oxide mediated vasodilation.
What proportion of endothelial cell vitamin D receptors are on the
apical surface, and so exposed to plasma 1,25OHD, plus any locally
secreted by immune cells there? What proportion are on the other
side (outside the vessel or capillary = basolateral) and so, I guess
less affected by the normal bone and calcium regulating level of
1,25OHD as a hormone, and more affected by the actions of immune cells
in the surrounding tissue?
See also ../obesity/
According to the
research I review there, the excess adipocytes of obesity express ACE2
receptors and so can be infected with SARS-CoV-2. These are in
the outer lining of the heart and there are also ectopic adipocytes in the cells which make up the alveoli
I had never heard of these, but assuming it is true, then obese people
would have further infection in their lungs combined with extra
Farid Jalali's hypothesis of serotonin (5-HT) playing a major role in COVID-19 lung pathology
In late June 2020, Farid Jalali released a text-only document:
in which he proposes that serotonin, especially that released by
platelets in the clotting cascade, plays a major role in making things
much worse in SARS-CoV-2 infected lungs. He suggests that the
normal clearance mechanisms, which are in the lungs themselves, can no
longer function, so serotonin builds up in the whole circulation
causing further trouble.
As with the above diagrammatic hypothesis, I think only a handful of
people - pulmonolgists and the like - could fully appreciate and
critique what he is proposing.
However, I understand enough of it to envisage these as possible
explanations for the extreme levels of damage which occur with the
worst symptoms of COVID-19.
"Vitamin D" does not appear in either of these documents. The big
question is why is there so much inappropriate inflammation in these
patients. Surely low vitamin D levels - anything below 40ng/ml
250HD - plays a role in this immune system dysfunction. I also
suspect that low boron plays a role as well. See: ../#08-boron
Respiratory epithelial cells convert 25OHD to 1,25OHD
Further to the discussion above on
intracrine and paracrine signaling of 1,25OHD, here is a pertinent
article, from 2008. The lead author is a critical care
pulmonologist in Iowa.
. . . primary lung epithelial cells express high baseline levels of
activating 1α-hydroxylase and low levels of inactivating
24-hydroxylase. The result of this enzyme expression is that
airway epithelial cells constitutively convert inactive
25-dihydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3.
Also, a 2011 article:
Toll like receptors (TLRs) respond to extracellular fragments of
pathogens and/or of cellular damage, upregulate CYP27B1
(1a-hydroxylase) which converts 25OHD to 1,25OHD. This activates
the vitamin D receptor (the production of which is also upregulated by
the activation of TLRs) and the activated receptor travels to the
nucleus and upregulates genes specific to the particular cell
type. This diagram depicts some of the actions. (I have
another diagram somewhere depicting autocrine 1,25OHD signaling between
He suggests 25OHD levels of 40 to 60ng
, which I agree with.
Angiogenesis; ACE2-positive lymphocytes. alveolar and endothelial cells
Also of interest is this analysis of
COVID-19 damage to lung tissue differs from that resulting from
H1N1 influenza in 2009:
The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9
times as prevalent in patients with Covid-19 as in patients with
influenza (P<0.001). In lungs from patients with Covid-19, the
amount of new vessel growth — predominantly through a mechanism of
intussusceptive [splitting] angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001).
Are these new blood vessels or capillaries fed by the pulmonary or
bronchial artery? To what extent were they clogged with
microthrombi? To what extent could they participate in gas
exchange? Although the accompanying editorial
notes that the H1N1 samples are not directly comparable, this graph
indicates that angiogenesis is a very prominent feature in
COVID-19. This analysis is from autopsies - so this progression
is for the patients with the worst symptoms.
79 inflammation-related genes
were differentially regulated only in specimens from patients with
Covid-19, whereas 2 genes were differentially regulated only in
specimens from patients with influenza; a shared expression pattern was
found for 7 genes.
This suggests to me a high immune system involvement, in addition to
direct viral damage, in both the COVID-19 and H1N1 affected
lungs. Low vitamin D drives inappropriate, self-harming,
overly-inflammatory responses, as well as weak antiviral defense
Loss of ACE2 receptors is a prominent part of Farid Jalali's hypothesis
(above), driving excessive angiotensin II. To what extent is this
due to direct viral damage (virus attaches to ACE2 which is then
internalised with the virus and so no longer remains active on the cell
membrane) or due to immune system destruction of infected cells, and
perhaps those nearby even if uninfected?
Why, in these illnesses are ACE2 receptors more frequently found on
epithelial and endothelial cells? Are these cells sensing
excessive blood pressure due to microthrombi blocking the capillaries
and/or vasoconstriction there? If so, do they sprout ACE2
receptors in an attempt to reduce angiotensin II levels and so reduce
If so, then these extra ACE2 receptors make them vulnerable to viral
infection and the whole situation can spiral out of control.
|Fraction of cells with ACE2 receptors
Why do ACE2 receptors appear on lymphocytes? Are these lymphocytes also
acting to reduce local angiotensin II to reduce vasoconstriction?
If so, then the virus is well adapted: it gets into cells which already
express the ACE2 receptor, taking these receptors, and then the cells,
out of action. This reduces angiotensin II levels, driving
vasoconstriction and microembolisms which cause multiple cell types
which normally express few, if any, ACE2 receptors to express lots of
them, in an attempt to reduce vasoconstriction - so the virus can
infect them too. Inducing lymphocytes to express ACE2 and so be
infected is quite a twist.
This article seems be relevant, mentioning ACE2-positive lymphocytes,
but I have not attempted to pursue this line of inquiry further.
Please suggest pertinent articles and discussions. ../#contact
Vitamin D and Endothelial Function
Your COVID-19 patients are (according to Philippino and Indonesian research I cite here cv19/
generally seriously deficient in vitamin D. Surely you can
improve their chances of survival with vitamin D supplements.
Cholecalciferol (D3) takes days to convert to 25OHD in the liver - and
the liver may not be functioning well. So high dose oral D3 -
such as 50,000 or 100,000IU, ideally with a meal including fats - when
they arrive in hospital, is one way to start. If you can do oral
of IV 25OHD (calcifideol = Rayaldee
then this would be faster. Most immune system cells require
plasma 25OHD for their internal synthesis of 1,25OHD to activate their
internal (intracrine) vitamin D receptor signaling. So the whole
of immune regulation depends on a good 25OHD level.
Other cells, such as endothelial cells, require 1,25OHD calcitriol at
their membrane bound vitamin D receptors, and so may not rely directly
on plasma 25OHD levels.
Please see this recent review article:
Adequate vitamin D activation of endothelial cells achieves numerous functions:
- Increase vasodilation by releasing NO.
- Bring more calcium into the cell and release it from internal
stores to activate eNOS which produces the NO and stop AG2 catabolizing
L-arginine so it can be used by eNOS.
NO is a primary vasoactive substance that works as a potent vasodilator in addition to other vasoprotective properties such as protection from vessel inﬂammation and lesion formation.
NO acts on adjacent vascular smooth muscle cells in a paracrine manner
and induces vascular muscle relaxation . . .
. . . protects the vessel from developing atherosclerosis by inhibiting platelet adherence and aggregation, and leukocyte activation.
The trinity of COVID-19: immunity, inflammation and intervention
Here is an excellent paper, from
researchers in Singapore and Liverpool regarding the role of
inappropriate, over-inflammatory, immune responses in severe symptoms
There's no mention of vitamin D - though deficiency in this clearly
drives weakened and dysregulated immune responses which allow disease
progression and which, as this article documents, drive a lot of the
damage which occurs. Nor is there any mention of coagulation or
vasoconstriction - both key elements in the material above, which was
developed after this late April article would have been finalised.
. . . aggressive inflammatory responses
strongly implicated in the resulting damage to the airways.
Therefore, disease severity in patients is due to not only the viral
infection but also the host response.
In addition, the vast release of cytokines
by the immune system in response to the viral infection and/or
secondary infections can result in a cytokine storm and symptoms of
sepsis that are the cause of death in 28% of fatal COVID-19 cases. In
these cases, uncontrolled inflammation inflicts multi-organ damage leading to organ failure, especially of the cardiac, hepatic and renal systems.
Pyroptosis is a highly inflammatory form of programmed cell death
that is commonly seen with cytopathic viruses. A wave of local
inflammation ensues, involving increased secretion of the pro-
inflammatory cytokines and chemokines IL-6, IFNγ, MCP1 and IP-10 into
the blood of afflicted patients.
Notably, there exists a highly inflammatory monocyte-derived FCN1+
macrophage population in the bronchoalveolar lavage fluid of patients
with severe but not mild COVID-19. Also, patients with severe
disease show a significantly higher percentage of CD14+CD16+
inflammatory monocytes in peripheral blood than patients with mild
disease. These cells secrete inflammatory cytokines that contribute to
the cytokine storm, including MCP1, IP-10 and MIP1α.
Unrestrained inflammatory cell infiltration
can itself mediate damage in the lung through excessive secretion of
proteases and reactive oxygen species, in addition to the direct damage
resulting from the virus. Notably, virus was found in T
lymphocytes, macrophages and monocyte-derived dendritic cells. Direct virus killing of lymphocytes could contribute to the observed lymphopenia in patients.
Viral infection in immune cells such as monocytes and macrophages can result in aberrant cytokine production, even if viral infection is not productive. The degree to which SARS-CoV-2 targets these cells remains poorly defined.
Understanding the precise drivers of immune dysfunction is crucial to
guide the application of appropriate immunomodulatory treatments.
Indeed. The pages you are reading explain most or all of this
immune system dysfunction in terms of individual genetic variation,
lack of helminths, some dietary excesses and some very common
nutritional deficiencies - especially vitamin D, boron, omega-3 fatty
acids, vitamin C and potassium.
COVID-19: the vasculature unleashed
Here's another article concerning
endothelial failure in the lungs, with the researchers not knowing why
this happens to some people.
I wonder who created this beautiful illustration.
During homeostasis, the endothelium, surrounded by mural cells (pericytes [W]), maintains vascular integrity and barrier function. It prevents inflammation by limiting EC - immune (EC = Endothelial Cell) cell and EC - platelet interactions and inhibits coagulation by expressing coagulation inhibitors and blood clot-lysing enzymes and producing a glycocalyx (a protective layer of glycoproteins and glycolipids) with anti-coagulation properties.
Interestingly, recent studies using single-cell transcriptomics revealed endothelial
phenotypes that exhibit immunomodulatory transcriptomic signatures
typical for leukocyte recruitment, cytokine production, antigen
presentation and even scavenger activity. Compared with ECs from
other organs, lung ECs are enriched in transcriptomic signatures
indicating immunoregulation, and a subtype of lung capillary ECs
expresses high levels of genes involved in MHC class II-mediated
antigen processing, loading and presentation.
After the initial phase of viral infection, ~30% of hospitalized patients with COVID-19 develop severe disease with progressive lung damage, in part owing to an overreacting inflammatory response.
These would be mainly the patients with
the weakest and most dysregulated immune systems - the primary,
currently known (I suspect boron deficiency as well) preventable cause
of which is vitamin D deficiency. Yet vitamin D is not mentioned
in this article.
Mechanistically, the pulmonary complications result from a vascular barrier breach, leading to tissue oedema (causing lungs to build up fluid), endotheliitis, activation of coagulation pathways with potential development of disseminated intravascular coagulation (DIC) and deregulated inflammatory cell infiltration.
Reduced ACE2 activity indirectly activates the kallikrein–bradykinin pathway, increasing vascular permeability.
Immune cells, inflammatory cytokines and vasoactive molecules lead to enhanced EC contractility and the loosening of inter-endothelial junctions. In turn, this pulls ECs apart, leading to inter-endothelial gaps. Finally, the cytokines IL-1β and TNF activate glucuronidases that degrade the glycocalyx
but also upregulate hyaluronic acid synthase, leading to increased
deposition of hyaluronic acid in the extracellular matrix and promoting
fluid retention. Together, these mechanisms lead to increased vascular permeability and vascular leakage.
Vascular integrity and EC death leads to exposure of the thrombogenic basement membrane and results in the activation of the clotting cascade.
"Finally" just refers to this initial
stage of the zombie apocalypse which overcomes all these cell types in
the lungs. Note that in the description so far, and in what
follows, there is little or no mention of viral activity. Most
people deal with the virus pretty well, and things never get as bad as
just described. If you have read this page and most of the ../cv19/
page you will be at least roughly aware of the protective, largely vitamin D dependent
mechanisms in these cells which protect them from damage by pathogens,
and disallow the storm of destruction described so well here, which is
primarily driven by a weakened and dysregulated immune response.
ECs activated by IL-1β and TNF initiate coagulation by expressing
P-selectin, von Willebrand factor and fibrinogen, to which platelets bind.
In turn, ECs release trophic cytokines that further augment platelet
production. Platelets also release VEGF, which triggers ECs to
upregulate the expression of tissue factor, the prime activator of the coagulation cascade, which is also expressed by activated pericytes. In response, the body mounts countermeasures to dissolve fibrin-rich blood clots, explaining why high levels of fibrin breakdown products (D-dimers) are predictive of poor patient outcome. As a result of the DIC and clogging/congestion of the small capillaries by inflammatory cells, as well as possible thrombosis in larger vessels, lung tissue ischaemia develops, which triggers angiogenesis and potential EC hyperplasia. While the latter can aggravate ischaemia, angiogenesis can be a rescue mechanism to minimize ischaemia. However, the newly formed vessels can also promote inflammation by acting as conduits for inflammatory cells that are attracted by activated ECs.
We're not done yet . . .
Many patients with severe COVID-19 show signs of a cytokine storm. The high levels of cytokines amplify the destructive process by leading to further EC dysfunction, DIC, inflammation and vasodilation of the pulmonary capillary bed.
This explanation differs from that of Farid Jalali's #2020-Jalali-b
above - in which angiotensin II levels force vasoconstriction.
The above words seem to indicate that the unspecified mechanisms of
vasodilation (I guess nitric oxide, as noted above) prevail.
This results in
alveolar dysfunction, ARDS with hypoxic respiratory failure and
ultimately multi-organ failure and death.
EC dysfunction and
activation likely co-determine this uncontrolled immune response.
Yes, but why? This is where
anyone who has read the research I have read - and which you will read
if you follow my links - thinks of the low 25OHD levels of these
patients, and how this will reduce the ability for numerous types of
immune cell (and it seems we should count some or all endothelial cells
as immune cells too) to act strongly and successfully against the
virus, while regulating the destructive responses which cause almost
all the harm described in this article.
is because ECs promote inflammation by expressing leukocyte adhesion
molecules, thereby facilitating the accumulation and extravasation of
leukocytes, including neutrophils, which enhance tissue damage. This
is because ECs promote inflammation by expressing leukocyte adhesion
molecules, thereby facilitating the accumulation and extravasation of
leukocytes, including neutrophils, which enhance tissue damage. [Neutrophils are one of the immune system's professional phagocytes. W]
Moreover, we hypothesize that denudation of the pulmonary vasculature
could lead to activation of the complement system, [W] promoting the
accumulation of neutrophils and pro-inflammatory monocytes that enhance
the cytokine storm.
As I wrote on the main page cv19/
most of the death resulting from influenza is also due to weakened,
dysregulated, immune systems, with the same primary causes (cv19/#helminthsgone
lack of helminths, individual genetic variation, dietary excesses and
nutritional deficiencies, most particularly of vitamin D.
This is based on the observation that during
influenza virus infection, pulmonary ECs induce an amplification loop,
involving interferon-producing cells and virus-infected pulmonary
epithelial cells. Moreover, ECs seem to be gatekeepers of this [destructive and quite likely deadly] immune
response, as inhibition of the sphingosine 1 phosphate receptor 1
(S1PR1) in pulmonary ECs dampens the cytokine storm in influenza
infection. This raises the question whether pulmonary ECs have a
similar function in the COVID-19 cytokine storm and
whether S1PR1 could represent a therapeutic target. Another unexplained
observation is the excessive lymphopenia in severely ill patients with
COVID-19 and whether this relates to the recruitment of lymphocytes
away from the blood by activated lung ECs.
Yes they are a therapeutic target -
along with every other type of cell in our bodies. Everyone
should run their bodies better by giving all their cells the nutrients
they require for proper operation. This starts with 40 to 60ng/ml
When they don't do this, and their levels are 30ng/ml or less, sometimes down to 10ng/ml or less (and see ../#21authors
for an article written by 21 experts who regard vitamin D deficiency as
being only below 10ng/ml) they can get by - until a virus, bacteria or
some other insult triggers this weak and dysregulated immune
response. Then they suffer sepsis, pneumonia etc. - or in the
case of COVID-19 and even worse horror story because of the way the
virus, during this self-destructive cascade, infects immune cells which
respond to the troubles by expressing ACE2 receptors, driving a
hypercoagulative storm which wreaks likely permanent harm all over the
When people get to hospital, in these conditions, the first thing
doctors should do is try to raise their 25OHD levels to something
healthy, like 40ng/ml. Perhaps it will be too late, but I am
exceedingly perplexed, spending these months knowing how low 25OHD is
not being treated, and is condemning hundreds of thousands of people to
terrible suffering, lasting harm and death.
We should remember that the wholesale 1kg ex-factory cost of D3 for 4000IU a day is US 9 cents per year.
All these people are boron deficient too. Boron's half life is 20
hours or so, and they start of boron deficient in ordinary life,
getting about 1mg or so a day, and become even more deficient in
hospitals since doctors don't even recognise it as a nutrient.
Yet boron has numerous anti-inflammatory properties, similar to vitamin
D, but also in some ways unique to itself.
100mg of borax a day gives 11.4mg boron a day, which is surely
sufficient for repletion. This is 36 grams of borax a year, which
costs (retail, USD$10/kg) US 36 cents per year.
circumstantial evidence suggests a link between ECs, pericytes and
COVID-19. First, risk factors for COVID-19 (old age, obesity,
hypertension and diabetes mellitus) are all characterized by
pre-existing vascular dysfunction with altered EC metabolism. As
hijacking of the host metabolism is essential for virus replication and
propagation, an outstanding question is whether EC subtypes or other
vascular cells in specific pathological conditions have a metabolic
phenotype that is more attractive to SARS-CoV-2.
Old age - in the absence of 4000IU or more D3 a day supplementations -
is strongly correlated with even lower 25OHD levels than is normal
middle age. These risk factors are caused, in large part, by
vitamin D and other deficiencies, the lack of helminths etc. and
excessive dietary fats, sugars and other carbohyrates, and frequently
lack of proper exercise.
So even if the actual conditions were not risk factors in themselves
(and they are, especially obesity) then the correlation between these
conditions and risk for serious COVID-19 symptoms would be to a large
extent explained by a lifetime of inadequate vitamin D.
occasional clinical reports suggest an increased incidence of Kawasaki
disease, a vasculitis, in young children with COVID-19.
I had never heard of Kawasaki disease. It took me less than a
minute with Google Scholar, searching for it with "vitamin D" to find
the article I link to here ../#2015-Stagi
which shows that the only children who suffer and die from this
terrible condition have exceedingly low (rickets levels) of 25OHD.
Other articles on COVID-19 endothelial pathology
There are no doubt other articles with detailed accounts of COVID-19
pathology in the epithelium of the lungs. I don't have time to
find or read them all, but here are some of potential interest:
Vitamin K depletion in severe COVID-19 contributing to coagulation?
I haven't read this yet. Would
vitamin K supplementation reduce the most destructive aspect of severe
COVID-19: the hypercoagulative state?
COVID-19 Protocol for early intervention to reduce cytokine storm
and so reduce or eliminate the deadly hypercoagulative state
The website of the Front
Line COVID-19 Critical Care Working Group
Please follow all the links to protocol, press release and other
documents there, as well as documents linked from theirs:
in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of
Meduri & Chrousos
The original website was: https://recoverywithoutwalls.com/covidprotocol/
The protocol concerns the early
use of methylprednisolone, low molecular weight heparin, IV vitamin C
and hydroxychloroquine, before to reduce or prevent the development of
the cytokine storm which causes the hypercoagulative state which is
what harms and kills people. Other elements are nasal cannula
oxygen with prone positioning and avoidance of incubation as much as
possible. In late April, they added optional vitamin D to
their ICU protocol.
An excellent write-up by Caitlin Dickson: https://news.yahoo.com/...doctors-question-how-we-use-ventilators-123733204.html
The Marik Protocol
Paul Marik MD's basis for the abovementioned Task
This work is based on years of pre-COVID-19 development of new ways of
treating ICU patients whose immune system is overly inflammatory.
This involves early
use of IV vitamin C, methylprednisolone, low molecular weight heparin and numerous other compounds and approaches to care.
At this page there is also a 2020-05-28 video - which is actually at YouTube
- in which Professor Marik discusses COVID-19 in general and how he and
his team treat it. His part in the video starts at 45
At 50:30 he mentions vitamin D status as one of the factors affecting
COVID-19 outcomes - and the effect of high geographical latitude on low
vitamin D levels. In US states north of 40° there is a much
higher risk of COVID-19 mortality.
Marik 51:40: COVID-19 results in a very high expression of inflammatory
cytokines, chemokines, IL-6 and IL-1 [much more so than common
respiratory viruses, including influenza].
What makes this virus so unique and so smart is that while it
upregulates the inflammatory response, it downregulates the expression
Interferon type 1 and type 3 are the major host defenses against viral
infections. COVID-19, as opposed to influenza, results in a
limited antiviral response. So there is a marked imbalance between the
host immune response in getting rid of the virus and this profound inflammatory response.
There's lots more of interest
in this video - I am not going to try to transcribe it all. CRP
levels proportional to disease severity. SARS-CoV-2 organizing
pneumonia. Diffuse alveolar damage, fibroproliferative response,
vasculitis & thrombosis. Progression to irreversible damage -
so the need to treat early with an anti-inflammatory approach.
Correct time to introduce anti-inflammatory treatment. Vitamin C
EMCrit discussion on timing of corticosteroids
Josh Farkas and
commenters discuss the timing and strength of corticosteroid use with
Dr Cameron Kyle-Sidell's videos on how different COVID-19 is from
what he trained for
L. Gattinoni et al. on L and H "phenotypes"
Dr Farid Jalali's COVID-19 diagram concerning cytokine storm and
resulting hypercoagulative state
Farid Jalali https://twitter.com/farid__jalali
tweeted a detailed diagram https://twitter.com/farid__jalali/status/1247036001349849088
depicting the cytokine storm turning a moderately PAI-1 elevated
coagulative state, which apparently can be controlled with heparin,
into a hypercoagulable Progressive Thrombotic Cascade. The long
progression of this thrombosis apparently enables the oxygen levels to
drop slowly enough that the patient copes with it better than would be
the case with normal ARDS. This leads to microvascular thrombosis
in the lungs, heart, kidney, gut, pancreas, skin and CNS - and so
frequently to death.
He states that COVID-19 is cytopathic to the endothelium and that
this degenerates (as far as I know, in the absence of vitamin C etc.
treatment) into the Severe COVID-19 cytokine storm. This makes me
think that the vitamin C, corticosteroid etc. treatment prevents the
virus and the consequent (at least in these patients) immune response
doing so much harm to the endothelium.
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