VACCINES
New York Times COVID Vaccine Tracker
July 13th
Antibodies to the virus would increase sharply after infection and peak
after about two weeks. But then their presence would decline, generally
disappearing entirely somewhere between four months and one year.
May 24th the first human trial of a possible vaccine has been found to
be safe and may effectively fight the virus.
Scientists in China say 108 healthy adults were given a weakened strain of
Adenovirus to deliver genetic material which
codes for the SARS-CoV-2 spike protein to the cells. These cells then
produce the spike protein, and travel to the lymph nodes where the immune
system creates antibodies that will recognize that spike protein and fight
off SARS-CoV-2.
But 44%-56% of participants in the trial had high
pre-existing immunity
to
adenovirus
type 5, and had a
less positive
antibody and T-cell response to
the vaccine.
Oxford Mar 19: A vaccine against coronavirus could be ready as soon as
September !
“80 per cent confident” that the vaccine would work !
---The vaccine being developed at Porton Down is an
intramuscular injection that uses a harmless, non-replicating virus to
smuggle DNA from the coronavirus into the body’s cells.
---Once inside, the body’s cells use the coronavirus DNA to churn out copies
of the “spike proteins” that dot the germ’s surface. It is these that should
marshal the immune response against coronavirus infection. Previous studies
suggest the vaccine should work with only a single shot.
---Vaccines that operate the same way have been used safely in thousands of
people, aged from one week old to 90 years, for diseases ranging from
malaria and TB to Mers, (another coronavirus), and Ebola, for which
it is now being deployed in Uganda and the Democratic Republic of the Congo.
--The Oxford trial is expected to recruit people from a range of ages, but
scientists will be particularly keen to see how it performs in older people.
They are most vulnerable to the virus, but tend to respond less well to
vaccinations because of their weaker immune systems.
The Oxford vaccine, known as ChAdOx1, is one of five frontrunner
vaccines in development around the world.
The US biotech Moderna gave its first vaccine shot to a person in
Seattle April. Another US firm, Inovio, will soon start trials on its
own coronavirus vaccine, which requires a special device to administer
through the skin.
In Germany, CureVac is working on a vaccine, while others are in
development in China.
Human testing for Johnson & Johnson
coronavirus vaccine this fall
Moderna
has already moved into human
trials for
its vaccine candidate, as has China's
CanSinoBIO.
April 7th STUDY: COVID-19 vaccine
candidate shows promise in first peer-reviewed research by University of
Pittsburgh
April 7th STUDY: Trial drug can significantly block early stages of
COVID-19 in engineered human tissues -U. British Columbia -
Apeiron Biologics
ANTIBODIES
-
Vir Biotechnology (VIR)
has partnerships with GlaxoSmithKline (GSK)
and Biogen (BIIB).
-
Amgen (AMGN)
and small biotech partner Adaptive
Biotechnologies (ADPT)
are seeking antibody drugs.
-
Regeneron
and
Lilly
are also testing antibody-based coronavirus treatments.
-
Sorrento Therapeutics (SRNE)
preclinical testing"100% inhibition" of Covid-19 — within four days".
The Chronology of COVID-19 Mutation
around the world
The reason we need a new flu vaccine each season is that the flu mutates
quickly.
Fortunately, so far the virus that causes COVID-19 mutates more slowly.
But as the above image from Nextstrain.org shows, COVID-19 changes
rapidly enough that it’s likely whatever vaccine we
develop will need to be updated and readministered periodically.
VIRUS RELATED COMPANIES
Symbol PRICE M
SRNE Sorrento Therapeutics, Inc. 6.96
ABT Abbott Laboratories 91.05
JNJ Johnson & Johnson 150.87
ZM Zoom Video Communications, Inc. 165.5
DHR Danaher Corporation 163.96
TAK Takeda Pharmaceutical Company Limited 18.92
SNY Sanofi 47.50
REGN Regeneron Pharmaceuticals, Inc. 565.55
GILD Gilead Sciences, Inc. 75.02
VIR Vir Biotechnology, Inc. 38.80
MRNA Moderna, Inc. 83.74
HSIC Henry Schein, Inc. 56.60
NVAX Novavax, Inc. 56.37
INO Inovio Pharmaceuticals, Inc. 13.86
AHPI Allied Healthcare Products, Inc. 12.50
NNVC NanoViricides, Inc. 8.90
CODX Co-Diagnostics, Inc. 17.66
APT Alpha Pro Tech, Ltd. 13.52
LAKE Lakeland Industries, Inc. 13.53
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Aug
2021 lactoferrin, a protein found in
human breastmilk that is also available over the counter as a dietary
supplement derived from cow's milk.
"We found lactoferrin had remarkable efficacy for preventing infection,
working better than anything else we observed," Sexton said. He adds that
early data suggest this efficacy extends even to newer variants of
SARS-CoV2, including the highly transmissible Delta variant.
Mar 11th 2021 Vir and its partner, GlaxoSmithKline (GSK), said that the
drug, called VIR-7831, reduced
hospitalization and death by 85% in the trial, which is testing in early
Covid-19 patients with mild to moderate illness who are at high risk of
progressing to severe disease.
Asking the U.S. Food and Drug Administration for emergency- use
authorization
Regeneron Pharmaceuticals (REGN)
and Eli
Lilly (LLY)
both already have emergency-use authorizations for their own Covid-19
antibody
therapies, all for early-stage Covid-19 patients at high risk of severe
disease.
Mar 7th Fluvoxamine,
a drug commonly used to treat obsessive-compulsive disorder, has had to
becoming an early treatment candidate for COVID-19. Out of the 80 people who
received fluvoxamine, none, zero of them deteriorated nor went to hospital
versus -- 8% of those who got placebo(one died).
Jan
26th 2021
Aplidin
or
Plitidepsin,
(drugs developed to fight multiple myeloma) is
27.5 times more effective at treating COVID-19 than remdesivir
Jan 8th 2021 Two rheumatoid arthritis drugs that suppress the immune
system, tocilizumab and
sarilumab, for use in patients in intensive
care units. The relative risk of death was reduced by 24 percent when given
to people within 24 hours of admission,
Jan 1st 2021 Israel has distributed the first of two vaccine doses to
more than 10 percent of its population. Israel’s heavily digitized,
community-based health system — all citizens, by law, must register with one
of the country’s four H.M.O.s — and its centralized government have proved
adept at orchestrating a national inoculation campaign.
Apr 15th
an antioxidant known as "extracellular superoxide dismutase" (EcSOD).
This potent antioxidant hunts down harmful free radicals, protecting our
tissues and helping to prevent disease. Our muscles naturally make EcSOD,
secreting it into the circulation to allow binding to other vital organs,
but its production is enhanced by cardiovascular exercise.
even a single session of exercise
increases production of the antioxidant,
Dec 3rd A new antiviral drug, MK-4482/EIDD-2801 or
Molnupiravir, completely suppresses virus
transmission within 24 hours.
It is also potent against influenza. It can be taken by mouth.
Nov 13th Screening patients for autoantibodies
against interferons could help predict
which patients are more likely to become very sick !
Giving these patients a different type of
interferon — one not disabled by their genes or
autoantibodies — might help them fight off
the virus.
A pilot study of 98 patients found benefits from an inhaled form of
interferon. Hospitalized COVID patients
randomly assigned to receive interferon beta-1a
were more than twice as likely as others to recover enough to resume their
regular activities.
Future studies should test patients’ blood for genetic mutations and
autoantibodies against interferon, to
see if they respond differently than others.
inhaled interferon may work
better than an injected form of the drug because it’s delivered
directly to the lungs.
While injected versions of interferon have been used for years to
treat other diseases, the inhaled version is still experimental and
not commercially available.
And doctors should be cautious about interferon
for now, because a study led by the World Health Organization found
no benefit to an injected form of the drug in COVID patients. In
fact, there was a trend toward higher mortality rates in patients given
interferon, although this finding could
have been due to chance.
Giving interferon later in the course of
disease could encourage a destructive immune overreaction called a
cytokine storm, in which the immune system does more damage than the
virus.
Nov 5th For BLOOD CLOTS -
dipyridamole, which is approved to treat strokes and prevent
blood clots in people who receive mechanical heart valves, to reduce
the risk of clotting
Sep 8th How the Aging Immune System Makes Older People
Vulnerable.......when they took an anti-inflammatory drug for four days
before being injected, their immune responses improved.
But the steroid
dexamethasone,
a potent anti-inflammatory, has been shown to reduce deaths from the virus.
It resulted in one-third fewer deaths in people on ventilators and one-fifth
fewer deaths in those on oxygen,
Sep 3 2020 Corticosteroids (
dexamethasone
or
hydrocortisone
)reduce risk of death by 20% in critically ill
COVID-19 patients
Aug 10th
July 20th
an inhaled formula of the protein
interferon beta
gave a 79% lower risk of developing the severe disease.
July 18th
Cholesterol-lowering meds
have potential to downgrade COVID-19's threat . By allowing lung cells to
burn more
fat,
Fenofibrate
breaks the virus' grip on these cells, and prevents SARS CoV-2's ability to
reproduce. In fact, within only five days of treatment, the virus almost
completely disappeared.
July 15th NYT Coronavirus Drug and Treatment Tracker
July 6th
Excessive production of VWF(Willebrand factor) can lead to the development
of thrombosis, including in the capillaries of the lungs and inflammation
of the walls of blood vessels and capillaries.
July 1st
attach ACE2 to the end of an
synthetic antibody
MDR504
and Sars2 attaches to it instead of the
ACE2
on our cells. The ACE2 on the synthetic antibody out-competes the ACE2 on
our cells for the virus's attention .
June 26th
Seem likely to work because they block the chemical signals that activate
filopodia
production.
Among the 7 drugs identified are:
-
Silmitasertib,
a still-experimental drug in early clinical trials as a treatment for bile
duct cancer and a form of childhood brain cancer;
-
Ralimetinib,
a cancer drug developed by Eli Lilly; and
-
Gilteritinib (marketed
as
Xospata),
a drug in use already to treat acute myeloid leukemia.
June 16th
2,000 hospital patients were given
Dexamethasone and compared with more
than 4,000 who were not. For patients on ventilators, it cut the risk of
death from 40% to 28%. For patients needing oxygen, it cut the risk of death
from 25% to 20%.
It aids acclimatization at high-altitude.
It has saved mountaineers in trouble high on a peak.
It “brings life to a dead person,” said Everest guide
June 10th
Eli Lilly --
28 days of daily treatment with 4 mg of
Baricitinib
(
Olumiant) a
rheumatoid arthritis drug.
It may inhibit the host cell proteins that assist in viral reproduction,
reducing the ability of infected cells to make more of the virus.
-- such as Roche’s Actemra and
Regeneron and Sanofi’s
Kevzara,
are also being studied as a potential treatment for the cytokine storms
June
9th
The results of clinical trials of the drug, initiated on April 24,
demonstrate that
Levilimab
therapy can significantly reduce mortality.
(Russia)
June 5th
Acalabrutinib,
(FDA-approved for the treatment of several types of B cell cancers), improved
the oxygenation levels and decreased molecular markers of inflammation in a
majority of 19 patients hospitalized
June 3rd
a newly discovered natural antibiotic,
Teixobactin,
could be effective in treating bacterial lung conditions such as
tuberculosis and those commonly associated with COVID-19.
June 1st
Eli Lilly -- Neutralizing
Antibodies to lower the virus -- infuse patients with an antibody,
giving it over 30 minutes intravenously. It will stay in the body for weeks.
May 28 Already proven safe in Clinical Trial of 700 -- treatment for
Blood Clotting AND Inflammation - ARCA Biopharma -
AB201 (rNAPc2)
May
27th
An
antiviral
called
EIDD-2801,
has shown promise against several RNA viruses, including Ebola, influenza
and SARS-CoV-1, in cell and animal studies.
EIDD-2801 targets the same viral enzyme as
remdesivir(which
must be given intravenously), EIDD-2801 is an
oral
medication which could be taken at home rather than in the hospital,
allowing treatment
earlier.
May 27: Anti-inflammatories may keep coronavirus from replicating
Researchers in Spain using computer techniques have analyzed 6,466 approved
drugs and identified seven that might inhibit the main enzyme that helps the
coronavirus to replicate, referred to as M-pro.
The approach is already being tested via trials of the HIV antiretroviral
medications lopinavir and
ritonavir.
Two of the seven newly identified drugs, both anti-inflammatory medications,
have been selected for early-stage laboratory tests.
- celecoxib,
sold by Pfizer Inc for arthritis pain under the brand name Celebrex,
and
- carprofen,
used for pets under several brand names, including Rimadyl from
Zoetis Inc.
The researchers say the molecular
structures of these drugs could be used as starting points for developing
derivatives with more potent effects against the coronavirus.
May 24 Injecting neutralising antibodies into infected mice, after five
days the viral load was reduced by a factor of 2,500. The drug's antibodies
are produced by the human immune system (to prevent the virus infecting
cells) — isolated from the blood of 60 recovered patients.
Plasma
is limited in supply but these 14 neutralising antibodies could be put into
mass production
quickly.
May 20th
treatment with so-called type-1
interferon
“could stop the virus before it could get established,
May
13 Global
study using
AI
to examine COVID-19 patient data from 300 intensive care units (ICU)
May
13 How COVID-19 kills
May 12 STUDY: Treatment with Senicapoc can
prevent SARS and the lung damage seen in COVID-19....., we don't treat the
viral infection, but we prevent or slow the development of the disease that
leads to severe damage to the lungs,
May
12: Lipid
Mediators
derived from
omega-3
fatty acids serve as the body's natural "stop" signals to inflammation. ..
already in clinical trials for other inflammation-driven disease ,,,
May
12
CAP-1002,
contains cardiosphere-derived cells (CDCs)
that are grown in the laboratory from human heart tissues. .... originally
created to treat heart failure, can help the whole body.
4 of 6 critically ill ... discharged from the hospital.
5
were on ventilators. Within four days after infusion with CAP-1002, 4
patients were able to breathe without respiratory support
May
8th Of more than 1,600 patients between late February and mid-April., 84
patients received 10–40 mg of intravenous
Famotidine
(Pepcid
Heartburn med.) daily over 6 days.
Those who got
Famotidine
fared better.
They were far less likely to die or require a ventilator—a
twofold decrease in risk.
May
8th
A two-week course of antiviral therapy with
-
interferon beta-1b
-
lopinavir-ritonavir
-
ribavirin,
started within 7 days of showing COVID-19 symptoms, is safe and more
effective at reducing the duration of viral shedding than
lopinavir-ritonavir
alone in patients with mild to moderate illness,
May 7th Lancet: With ageing, malnutrition, immunosuppression, and
co-morbid states, our immune system loses the
ability to adapt to novelty.
But the child's immune system is prepared and fit to
react to novelty, a function that might be
diminished in adults and ineffective in elderly people aged 70 years or
older.
Children have the ability to rapidly
produce natural antibodies with broad reactivity that have not yet been
selected and shaped by the reaction to common environmental pathogens over
time.
In infants and children, crucial parts
of the immune system are highly adaptable to new
antigens.
In contrast, in the elderly, those parts are replaced with the highly
mutated and specific, they recognise their targets but appear incapable of
adaptation to new antigens.
The child immune response might have the
double function of secreting cytokines.
A potent anti-inflammatory cytokine is produced reducing immune-mediated
tissue damage, in particular, in the lung.
May 6th
baricitinib,
as a possible treatment ?
May
4th:
computer-aided drug design to examine the effectiveness of
-
remdesivir,
-
5-fluorouracil,
-
ribavirin
-
favipiravir
in treating COVID-19. All four drugs were effective in inhibiting, or
blocking, the coronavirus' RNA proteins from making genomic copies of the
virus.
May 1st REMDESIVIR
Follow-on Study: " suggests it may be possible
to develop broad spectrum antiviral inhibitors. ..... theoretical support
for the design of more powerful, efficient and specific ..... COVID-19
antiviral drugs.
May
1st
"We should pay more attention to
T cell counts
and their function, rather than
respiratory function
of patients," ... identifying drugs that recover T cell numbers and boost
function....Tocilizumab
is an existing drug that may be effective
May
1 Wean patients from ventilators: A big problem with inflating the lungs
using positive pressure to deliver oxygen is that
high pressure causes ventilator-induced lung injury, and in
COVID-19 patients this may compound the lung damage caused by the virus.
"In contrast, pacing the diaphragm distributes the breathed oxygen more
evenly throughout the lungs and this helps protect the tissue from
mechanical injury."
A second problem is that mechanical ventilation sidelines the
diaphragm muscle and causes it to
rapidly atrophy, which is a major reason
for failure to wean. "Pacing the diaphragm helps maintain or restore its
size, strength and endurance, which is key to enabling successful weaning,"
he says.
The diaphragm stimulation therapy is delivered through a central venous
catheter (CVC), similar to central lines currently placed in mechanically
ventilated ICR patients.
The unique central line is used to deliver both fluids and medications,
while also incorporating electrodes that activate the diaphragm muscle,
via transvenous phrenic-nerve stimulation.
Apr
30
"In addition to pneumonia affecting the small air sacs within the lungs, we
are also finding
hundreds of small blood clots throughout the lungs.
This scenario is not seen with other types of lung infection, and explains
why
blood oxygen levels fall
dramatically in severe COVID-19 infection.
Apr
30th
Proven
cardiovascular anti-inflammatory therapies
should be used to treat COVID-19 patients that are at risk of, or have
developed, cardiovascular problems,
"Inflammation plays an important role in the development and complications
of cardiovascular diseases and we have seen that COVID-19 patients with
greater signs of an inflammatory response are more likely to suffer
serious cardiovascular events and are at greater risk of dying,"
".... The virus could directly infect and cause
inflammation of the heart's tissues, aggravate existing cardiovascular
problems, or trigger an over-excessive immune response
in the body, often referred to as a 'cytokine
storm',
which leads to the body attacking itself."
Apr 30th
"ACE2
keeps the substance
bradykinin
under control.
Bradykinin
makes blood vessels leak.
We have good reason to believe that with COVID-19 infections we see exactly
this effect: when the virus is introduced,
ACE2
receptors
disappear from the lung cells, giving
bradykinine
free rein in
causing the small blood vessels to leak massively
at the site of infection."
The problems of
vascular leakage
can be aggravated by an
inflammatory phase.
This causes even
more leakage
and damage to the lungs.
Anti-inflammatory drugs
can have a potentially dampening effect here, and doctors and researchers
all over the world are doing their best to select the most optimal drugs for
this stage. In addition the long lasting vascular leakage and inflammation
of the blood vessels will trigger the
coagulation
cascade leading to
thrombosis
and eventually
scarring
of the lungs.
Interventions that are
started early
to treat this
leakage
have the capacity to prevent these serious complications and might be
effective in keeping patients out of the ICU.
Apr
27: People with certain heart diseases may be more
susceptible to worse outcomes with COVID-19, but the reason why has remained
unknown. Patients with one specific type of heart disease obstructive
hypertrophic cardiomyopathy (HCM) the heart increases production of the
ACE2 RNA transcript and the translated ACE2 protein.
Normally, this pathological response at the cellular level might be the
heart's attempt to compensate for changes caused by disease. Unfortunately,
COVID-19, hijacks these ACE2 receptors on the membrane of
cells and uses them to get inside the cells. The virus not only gains entry
through ACE2, but also it takes this protein with it, removing
a protective signaling pathway that normally counters the negative impact of
the hormone angiotensin II. This hormone increases
blood pressure and leads to
fluid retention.
Apr
27:
device that does the work of the lungs by
removing carbon dioxide
from the blood
Apr 24
New research finds a connection
between destructive white blood cells and a more severe disease
course in patients with COVID-19.
"Patients with COVID-19 infection have higher blood
levels of neutrophil extracellular traps, also called
NETs, which are a product of an inflammatory type of neutrophil cell
death called NETosis," The researchers
analyzed blood samples from 50 patients
with COVID-19 ....... to better understand what causes the
inflammatory storm and
blood clots .. They believe NETs may
be relevant given that thrombosis
and inflammation are hallmarks .
Apr 23 Recent observations suggest that respiratory failure in
COVID-19 is not driven by the development of the acute respiratory distress
syndrome alone, but that microvascular thrombotic
processes may play a role.
There is a strong association between D-dimer levels, disease
progression and chest CT features suggesting
venous thrombosis.
In addition, various studies in patients with COVID-19 have shown a very
strong association between increased D-dimer levels and severe
disease/poor prognosis.
Careful attention needs to be paid to the initial diagnosis and treatment of
the prothrombotic and thrombotic state that can occur in a
substantial percentage of COVID-19 patients.
"Imaging and pathological investigations confirmed the COVID-19 syndrome is
a thrombo-inflammatory process that initially affects lung
perfusion, but consecutively affects all organs
of the body," . "This highly thrombotic syndrome leads to
macro-thrombosis and
embolism. Therefore, strict thrombosis
prophylaxis, close laboratory and appropriate imaging monitoring with
early anti-coagulant therapy in case of suspected venous
thromboembolism are indicated."
Recommendations:
Findings have also emerged linking COVID-19 more specifically with
pulmonary embolism
"See:- "Why
Some Doctors Are Now Moving Away From Ventilator Treatments"
April 13:
Virology lab finds drug
Remdesivir
originally meant for Ebola is effective against a key enzyme of coronavirus
that causes COVID-19 |