Research ProposalPDF Available

CORONA VIRUS/Covid-19 ACUTE RESPIRATORY DISTRESS SYNDROME ************************************************* HIGH DOSE IV METHYLCOBALAMIN IS A SAFE & COST EFFECTIVE RESCUE TREATMENT for ARDS

Authors:
  • University of Oxford St Catherine's College

Abstract

Corona Virus/ Covid-19/ SARS-Cov-2 has ground the world to a halt and is showing up the deficiencies of our health care systems everywhere, and the vulnerability of the global population. When Covid-19 kills, it kills through Acute Respiratory Distress Syndrome/ ARDS which, in effect, kills by a sepsis related process. Thus ARDS is fuelled by the proverbial "cytokine storm" of sepsis. It has also been reported that people who die of Covid 19 ARDS have a depletion of Natural Killer/NK cells,, and that severe cases of Covid-19 have significantly lower T lymphocyte counts with depressed immune function in general [Chen,
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CORONA VIRUS/Covid-19 ACUTE
RESPIRATORY DISTRESS SYNDROME
*************************************************
HIGH DOSE IV METHYLCOBALAMIN IS A
SAFE & COST EFFECTIVE RESCUE
TREATMENT for ARDS.
Dr Carmen Wheatley D.Phil., St Catherine’s College, Oxford
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Corona Virus/ Covid-19/ SARS-Cov-2 has ground the
world to a halt and is showing up the deficiencies of
our health care systems everywhere, and the
vulnerability of the global population.
When Covid-19 kills, it kills through Acute
Respiratory Distress Syndrome/ ARDS which,
in effect, kills by a sepsis related process.
Thus ARDS is fuelled by the proverbial
“cytokine storm” of sepsis. It has also been
reported that people who die of Covid 19 ARDS
have a depletion of Natural Killer/NK cells,,
and that severe cases of Covid-19 have
significantly lower T lymphocyte counts with
depressed immune function in general [Chen,
2020; Tan, 2020; Laing, 2020; Diao, 2019; Kuri-
Cervantes, 2020; Chen, 2020].
At this point in time, when the FDA have suddenly
relaxed many drug control regulations, in order to be
able to use off-label drugs in a desperate attempt to
mitigate disaster, the FDA actually already have
one powerful item in the armoury, to which,
because of its safety and cost-effectiveness, combined
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with efficacy, they granted Orphan Drug status some
years ago, for use in suspected terrorist CN gas
attacks. This Orphan Drug is vitamin B12 as
hydroxocobalamin for high dose intravenous
administration, the safest and most efficacious
cyanide antidote on the planet.
Indeed, in countries which use hydroxocobalamin B12
as their cyanide antidote of choice, such as France,
Italy and China, there is more than half a
century’s experience of safe and efficacious
use of high dose cobalamin in the ICU, with a
pharmacological drug safety profile second to
none.
For some time now I have been collaborating with
colleagues at the William Harvey Institute, London,
investigating in animal models the use of high dose IV
cobalamin for sepsis. A key (published) discovery is
that cobalamin is a central regulator of the immune
response, very specifically through timely modulation
of production of the universal second messenger, the
gas nitric oxide/ NO* [Sampaio, 2013]. This time-
dependent regulation of NO* by cobalamin has knock-
on, beneficial, strict regulatory effects on every aspect
of the pro- and anti-inflammatory phases of the
immune response. It ensures the impossibility of a
descent into the unresolved chaos of the
aforementioned “cytokine storms” of SIRS/ARDS/
sepsis and septic shock.
We are now concluding pre-clinical trial work,
defining more precisely the mechanisms by which
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high dose IV cobalamin confers protection in SIRS/
sepsis and septic shock.
ARDS is often a feature of sepsis and, as mentioned, is
driven by the self same unresolvable pro-
inflammatory response as sepsis .
Thus our research work is potentially very
applicable to ARDS/ Covid 19 crisis.
In yet to be published work, in which 6 different key
cobalamins were tested, we have discovered that high
dose methylcobalamin B12 is even more
efficacious in an animal model of sepsis than
is high dose hydroxocobalamin B12.
The protocol that I first discussed as potentially
suitable for SIRS/ sepsis/septic shock, -thus ARDS- in
a 2006 Medical Hypotheses paper, [available in full
on my Researchgate page], has been confirmed by our
William Harvey Institute animal model work to be, as
I predicted in 2006, the dose equivalent in a human
of the anti-cyanide hydroxocobalamin B12 treatment.
This treatment already exists in the old Merck
Serono ‘CyanoKit’, (approved also by EMA/ the
European Medicines Agency), and now owned
by Pfizer associated Meridian Medical
Technologies Inc.
Based on our collective research insights, and on my
knowledge of the wider cobalamin lab research, and of
the lost, or forgotten, alternative clinical uses of
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cobalamin literature, [going back to the 1950s], I
believe that:
The ideal RESCUE PROTOCOL FOR ARDS
would utilise 4 to 5 GRAMS of
methylcobalamin daily, administered by IV, in
saline, for anywhere between 1 to 5, or even 7
days, depending on response, as the safest and
pote ntially most efficacio us trea t ment
available for viral sepsis related ARDS.
Crystalline methylcobalamin is available
w o r l d w id e f r o m m a n y c om p o u nd i ng
pharmacies, and could be deployed on
compassionate grounds at these doses.
However, where it is impossible to obtain
methylcobalamin for the implementation of this
protocol,
Pfizer’s Meridian Medical Technologies ‘CyanoKit’,
which is licensed, would be a good second
best. (The only negative is that the Cyanokit supplies
the crystalline HOCbl in 5 gram vials, which may be
rather more than is needed to treat children or low
weight patients, so there could be some waste, which
would be avoided with compounded MeCbl titrated to
weight, which, in any case, is substantially cheaper).
This protocol has already been deployed
clinically in other diverse extreme scenarios:
my draft clinical trial protocol of cobalamin for sepsis
-which is available via Researchgate on request-, gives
references showing high dose IV cobalamin efficacy in
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clinical refractory vasoplegic syndrome, both in
cardiac surgery and during liver transplants; in carbon
monoxide/CO, hydrogen sulphide/H2S poisoning;
and nitrous oxide/N2O poisoning.
More pertinent to the way that Covid-19 kills, and how
high dose parenteral cobalamin can combat this, is the
known fact that cobalamin boosts Natural Killer
c e l l l e v e l s , i n c r e a s e s e f f i c i e n c y o f
phagocytosis, and is critical for the regulated
pro-inflammatory and anti-inflammatory
sequence of the immune response.
A forgotten literature also shows that high dose
parenteral cobalamin has antiviral actions,
includin g against HIV, (for whi ch t he
mechanism has been elucidated [Weinberg,
1995]), and it was used with clinical success in
Japan and in several European countries,
primarily Italy, to treat hepatitis between 1950
to the 1970s. The general immune regulating effects
of cobalamin have been demonstrated both in vitro,
and in clinical studies some of which go back decades.
[For extensive references in support of all the above
statements, please see my imminent allied
Researchgate pre-print to be posted in March 2021:
The Effects of Cobalamin on the Immune
Response].
Moreover, in 2008, some B12 chemists from South
Africa published a landmark study showing that
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cobalamins have direct anti-malarial action, up to 40
times stronger than chloroquine [Chemaly, 2008].
Whilst chloroquine may now have a questionmark
over it given its possible cardiac and other toxicity
issues, cobalamin has no toxicity issues, and could
also have an analogous direct effect on the SARS-Cov2
virus, since it is known to bind to RNA aptamers
[Lorsch, 1994].
Thus, all indications from the WHI research are that
HIGH DOSE IV COBALAMIN, in particular
methylcobalamin, is a rescue treament well worth
trying now
for the worldwide Covid-19 ARDS crisis.
COBALAMIN IS LICENSED, SAFE
AND COST EFFECTIVE.
There is nothing to lose and everything to gain.
Moreover, high dose methylcobalamin could also be
safely and easily deployed at lower high doses, by
intramuscular injection, -as per my draft
methylcobalamin for sepsis clinical protocol, - as
both a potential prophylactic, and a mitigating
treatment for Covid 19 cases that end up in
hospital, to prevent such patients proceeding
to full blown ARDS.
This would obviously take huge pressure off
our collapsing health systems worldwide.
7
NB Extensive Pharmacological Safety References,
dating back more than half a century, for the
clinical use of High Dose IV Hydroxocobalamin
B12 are included in my
draft Methylcobalamin for Sepsis prophylaxis and
treatment clinical trial protocol.
This B12 cobalamin sepsis protocol is now
available on my Researchgate page as work in
progress, and can be see on request.
*************************************************
PLEASE BRING THIS ARTICLE AND THE
R E L A T E D D R A F T P R O T O C O L O N M Y
RESEARCHGATE PAGE TO THE ATTENTION
OF ANY INTERESTED ICU PHYSICIAN
ANYWHERE IN THE WORLD.
If you wish to contact me more directly to discuss
implementation of this potential therapy, please email
me on:
wheatley.carmen@googlemail.com
I will be happy to help any doctor anywhere with the
compassionate grounds use of cobalamin for Covid-19.
%%%%%%%%%%%%%%%%%%%%%%%%%%%
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