Two common drugs, Chloroquine and Kaletra, found to kill Coronavirus;
but CDC & FDA bureaucracy wants to delay
Newsletter published on March 21, 2020
(1) Australian Coronavirus patients cured with Chloroquine (Malaria
drug) or Kaletra (HIV drug); no unexpected side effects
(2) Drug companies prepare to deliver tens of millions of Chloroquine
tablets (a cheap and a safe drug); FDA hesitant
(3) CNN Fact Check says 'Chloroquine has not been approved by the FDA to
treat the coronavirus'
(4) Kaletra (HIV drug) and Chloroquine: Australian researchers claim two
existing drugs could 'cure' COVID-19
(5) FDA statement: no, these drugs are not approved as treatments for
COVID-19
(6) Is it ok to use a drug that's not yet certified? Bureaucrats Fiddle
while Rome burns
(7) Hydroxychloroquine (HCQ) less effective than Chloroquine (CQ) in
inhibiting SARS-CoV-2; thanks to Zhengli Shi
(8) Hospitals are not waiting for the FDA bureaucrats: Chloroquine in
short supply as hospitals buy in bulk
(9) Military personnel given Flu vaccine were significantly more
susceptible to Coronavirus
(1) Chloroquine may offer a cheap cure from Coronavirus
- by Peter Myers, March 21, 2020
While the FDA fiddles and Rome burns, practical researchers in China,
France and Australia seem to have found cures for COVID-19 that are
cheap and readily available.
Thus depriving Big Pharma of windfall profits; perhaps that it why the
FDA does not sound very happy.
Chinese patients in Australia informed sceptical Australian doctors
about the methods found successful in China. That's what led to the
current breakthrough.
Chinese medicine uses both tradition, and a "suck it and see" approach,
whereas Western researchers eschew the common touch and stick to "known
facts", i.e, "Science". They are forgetting that Science is primarily
inductive, not deductive.
It seems incredible that CNN, and the MSM generally, would lecture Trump
for announcing the Chloroquine cure, when the FDA had not certified it
for this virus. Such certification would take months, during which time
millions more lives would be lost, the hospital system would break down,
and the economy would suffer trillions of $ damage.
Are we expected to forget that the CDC bureaucrats bungled the testing
process, allowing the virus to become established in the USA?
I found a bottle of old Chloroquine tablets, left over from years ago,
and took two today, as per the standard dosage to prevent Malaria. For
adults, that dosage is 2 x 250 mg tablets of Chloroquine Phosphate, once
a week after taking food; you take them on the same day each week.
I also found an unopened bottle of Quinoctal tablets; these were used
for locations where resistance to Chloroquine had built up. But I'll
take the Chloroquine for now.
It's important for me, because my blood type is A-; blood type A is the
most vulnerable to Coronavirus, and most liable to have a serious case,
whereas blood type O is much less likely.
My wife arrives from San Francisco in two days, and will be in isolation
for 14 days. Basically, we'll be living apart for that time. I feel that
the Chloroquine has given me a fighting chance of keeping the virus at
bay, should she bring it. Of course, I'll be using a mask and disposable
gloves when in proximity situations.
With two common and cheap drugs, Kaletra and Chloroquine, it looks as if
the Olympics can go ahead.
If you do take Chloroquine, note that it lowers your blood sugar. This
can be of use to diabetics. But stick to standard doses. I grow a
vegetable vine called Bitter Melon, which produces fruits like a
cucumber, except that they have bumpy 'warts' on the outside. You pick
them young, before the seeds inside turn red. The fruits of this vine
have a bitter taste like Chloroquine, and contain a closely-related
chemical. They are commonly eaten in Asian cuisine, but are also
medicinal, being a remedy for Diabetes. Unfortunately, my plants are not
fruiting at present, because of the dry weather, but if they were I
would try them as a medicine for Coronavirus.
Big Pharma tries to scare you from self-medicating with talk of
side-effects that might kill you, etc. But we can look such details up
on the internet, and take our own personal conditions into account. We
don't need that Accountant-called-a-"Doctor" as a middleman.
If people distrust the Medical Profession, they have only themselves to
blame. To fix their reputation, they could start by admitting that
vaccines are the cause of the explosion in autism. If you haven't seen
Vaxxed, download it at
But first, watch this Deleted Scene, which was left out of the main
film. This youtube takes less than 2 minutes:
(2) Australian Coronavirus patients cured with Chloroquine (Malaria
drug) or Kaletra (HIV drug); no unexpected side effects
Coronavirus Australia: Queensland researchers find 'cure', want drug
trial Some patients who tested positive for coronavirus in Australia
have already been treated with one of the drugs and "all did very, very
well," researchers say.
Sarah McPhee
MARCH 17, 20206:26AM
A team of Australian researchers say they've found a cure for the novel
coronavirus and hope to have patients enrolled in a nationwide trial by
the end of the month.
University of Queensland Centre for Clinical Research director Professor
David Paterson told news.com.au today they have seen two drugs used to
treat other conditions wipe out the virus in test tubes.
He said one of the medications, given to some of the first people to
test positive for COVID-19 in Australia, had already resulted in
"disappearance of the virus" and complete recovery from the infection.
Prof Paterson, who is also an infectious disease physician at the Royal
Brisbane and Women's Hospital, said it wasn't a stretch to label the
drugs "a treatment or a cure".
"It's a potentially effective treatment," he said.
"Patients would end up with no viable coronavirus in their system at all
after the end of therapy."
The drugs are both already registered and available in Australia.
"What we want to do at the moment is a large clinical trial across
Australia, looking at 50 hospitals, and what we're going to compare is
one drug, versus another drug, versus the combination of the two drugs,"
Prof Paterson said.
Given their history, researchers have a "long experience of them being
very well tolerated" and there are no unexpected side effects.
"We're not on a flat foot, we can sort of move ahead very rapidly with
enrolling Australians in this trial," Prof Paterson said.
"It's the question we all have – we know it's coming now, what is the
best way to treat it?"
Prof Paterson said positive experiences in the fight against coronavirus
have already been recorded overseas, citing China and Singapore. His
research team are confident they can start getting the drugs to patients
in a very safe way on home soil.
"We want to give Australians the absolute best treatment rather than
just someone's guesses or someone's anecdotal experiences from a few
people," Prof Paterson told news.com.au.
He said they hope to be enrolling patients by the end of March.
"And that way, if we can test it in this first wave of patients, we do
fully expect that there are going to be ongoing infections for months
and months ahead, and therefore we'll have the best possible information
to treat subsequent patients," Prof Paterson said.
"That's really our aim, to get real world experience in Australia."
He said the trouble with the data coming from China was that it wasn't
really gathered "in a very controlled way", given they were the
epicentre of the coronavirus outbreak at the time.
"Things were just chaotic," Prof Paterson said.
"There were these emergency hospitals being built and the system really
being very, very stretched."
One of the two medications is a HIV drug, which has been superseded by
"newer generation" HIV drugs, and the other is an anti-malaria drug
called chloroquine which is rarely used and "kept on the shelf now" due
to resistance to malaria.
He said the researchers want to study them in a "very meaningful way"
against the coronavirus to "try and alleviate that anxiety of Australians".
"There have already been patients treated with these in Australia and
there's been successful outcomes but it hasn't been done in a controlled
or a comparative way," Prof Paterson said.
The drugs would be given orally, as tablets.
Prof Paterson said patients would be asked to participate "as soon as
they're admitted" to hospital with the aim of beginning treatment "very
early on in their illness".
He said the research was sparked by Chinese patients, who were first
given the drug in Australia, showing their doctors information on the
internet about the treatment used overseas.
"Our doctors were very, very surprised that a HIV drug could actually
work against the novel coronavirus and there was a bit of scepticism,"
he said.
"That first wave of Chinese patients we had (in Australia), they all did
very, very well when they were treated with the HIV drug.
"That's reassuring … that we're onto something really good here."
The RBWH Foundation has established a Coronavirus Action Fund. By Monday
afternoon it had raised $30,000 of the desired $750,000 for the clinical
drug trials and other related medical research.
"The trials will start as soon as funding is secured," the fund states.
When asked why they had to put a call out money, Prof Paterson said they
"want to give as many people in Australia access to this" and can't take
doctors away from their normal work.
"The reality is that doctors are going to need to be concentrating on
their patients and we need to get a very strong research team across
Australia that can make sure that all the Is are dotted and the Ts are
crossed and make sure that it is a really high-quality study so that we
can be really confident in the results," he said.
"We did this with bushfires, this is an example where we're reaching out
to the public to put the financial support behind the study so it can
get underway.
"Fifty hospitals have expressed interest in participating and we expect
there may even be more to come."
(2) Drug companies prepare to deliver tens of millions of Chloroquine
tablets (a cheap and a safe drug); FDA hesitant
Novartis, Mylan and Teva to supply tens of millions of chloroquine
tablets to fight COVID-19
by Eric Sagonowsky | Mar 20, 2020 12:47pm
As efforts to discover new COVID-19 medicines roll on, President Donald
Trump and others this week focused attention on the decades-old malaria
drug chloroquine. Bayer got things rolling with an initial donation of
the drug, and now Novartis, Mylan and Teva are taking steps to deliver
tens of millions of tablets.
Chloroquine and hydroxychloroquine, a more tolerable formulation, are
not approved to treat COVID-19. Still, U.S. authorities and others are
exploring their potential following encouraging preliminary results.
In response, Novartis has pledged a global donation of up to 130 million
hydroxychloroquine tablets, pending regulatory approvals for COVID-19.
Mylan is ramping up production at its West Virginia Facility with enough
supplies to make 50 million tablets. Teva is donating 16 million tablets
to hospitals around the U.S.
At a press conference Thursday, President Trump said the U.S. is
planning to make the malaria drug available by prescription "almost
immediately." Because chloroquine isn't FDA-approved to treat COVID-19,
the president may have been referencing off-label use.
For his part, FDA chief Stephen Hahn stressed the need to learn more
about the potential treatment. It's important to get the "right drug" to
the "right patient" at the "right dosage" at the "right time," the
commissioner said. The wrong dose could actually hurt a patient's
condition, he added.
On Friday, NIAID director Anthony Fauci said there's no meaningful
evidence to date on chloroquine and COVID-19. Any evidence so far is
"anecdotal," he added.
RELATED: Trump talks drug progress amid COVID-19 pandemic, but FDA chief
Hahn urges caution
Meanwhile, the U.S. case count has jumped in recent days. As of Friday,
authorities reported more than 14,000 cases in the U.S. California and
New York have instituted statewide lockdowns.
The pledges from Novartis, Mylan and Teva follow Bayer's Thursday
donation of 3 million tablets. Together, the commitments represent
nearly 200 million chloroquine and hydroxychloroquine tablets for the
global COVID-19 response.
Following preliminary reports of the drug's efficacy, shares for Indian
drugmakers Cadila, Torrent and Ipca each jumped, the Economic Times
reports. Those companies can also produce the medicine.
While drugmakers aim to boost availability of the med,
hydroxychloroquine is already in short supply, according to the American
Society of Health-System Pharmacists.
RELATED: Bayer donates millions of tablets of chloroquine to help in
COVID-19 fight
Early studies of the medicine in COVID-19 patients have caught the
attention of healthcare experts and market watchers. In France, a
professor conducted a small study of the malaria drug in 24 patients
with novel coronavirus infections. Of those who received the medicine,
only 25% tested positive for the virus after six days, according to
en24. Meanwhile, of those who didn't receive it, 90% tested positive
after that timeframe. The French government now plans to run larger studies.
In a study published last month in Nature, authors wrote that
"chloroquine is a cheap and a safe drug that has been used for more than
70 years and, therefore, it is potentially clinically applicable against
the 2019-nCoV."
Aside from efforts to learn more about chloroquine, drugmakers and
collaborators are working on new R&D programs and looking to repurpose
existing medicines.
Follow these links to read more about drug and vaccine efforts underway.
(3) CNN Fact Check says 'Chloroquine has not been approved by the FDA to
treat the coronavirus'
Fact check: Trump wrongly claims FDA 'approved' drug chloroquine to
treat the coronavirus
By Daniel Dale
Updated 0051 GMT (0851 HKT) March 20, 2020
Washington (CNN)
President Donald Trump claimed during a White House briefing on Thursday
that the Food and Drug Administration had approved the "very powerful"
drug chloroquine to treat coronavirus.
Chloroquine is used to treat malaria, lupus and rheumatoid arthritis.
"It's shown very encouraging -- very, very encouraging early results.
And we're going to be able to make that drug available almost
immediately. And that's where the FDA has been so great. They -- they've
gone through the approval process; it's been approved. And they did it
-- they took it down from many, many months to immediate. So we're going
to be able to make that drug available by prescription or states," Trump
said.
He added: "Normally the FDA would take a long time to approve something
like that, and it's -- it was approved very, very quickly and it's now
approved, by prescription."
Facts First: Chloroquine has not been approved by the FDA to treat the
coronavirus -- and nor has any other drug, the FDA made clear in a
post-briefing statement that said "there are no FDA-approved
therapeutics or drugs to treat, cure or prevent COVID-19." Because
chloroquine has been approved for other purposes, doctors are legally
allowed to prescribe it for the unapproved or "off-label" use of
treating the coronavirus if they want. But its safety and effectiveness
has not been proven with regard to the coronavirus. FDA Commissioner Dr.
Stephen Hahn, speaking after Trump at the briefing, said that
chloroquine would be tested through a "large, pragmatic clinical trial"
with coronavirus patients.
The FDA said in the statement that it is working with government and
academic entities that are investigating whether chloroquine can be used
"to treat patients with mild-to-moderate COVID-19 to potentially reduce
the duration of symptoms, as well as viral shedding, which can help
prevent the spread of disease."
Studies are underway. Hahn emphasized that this study process is
necessary even though the coronavirus situation is urgent.
"We also must ensure these products are effective; otherwise we risk
treating patients with a product that might not work when they could
have pursued other, more appropriate, treatments," Hahn said in the
statement.
Pharmaceutical company Bayer announced on Thursday that it is donating 3
million tablets of its chloroquine phosphate drug, sold under the name
Resochin, to the US government.
"New data from initial preclinical and evolving clinical research
conducted in China, while limited, shows potential for the use of
Resochin in treating patients with COVID-19 infection," Bayer said in a
statement.
CNN's Jacqueline Howard, Michael Nedelman and Jamie Gumbrecht
contributed to this story.
(4) Kaletra (HIV drug) and Chloroquine: Australian researchers claim two
existing drugs could 'cure' COVID-19
Have they found a cure for the coronavirus? Australian researchers claim
two existing drugs could 'cure' COVID-19 after patients they tested
responded 'very well' to treatment Researchers believe they've found a
cure for the latest strain of coronavirus The disease has killed more
than 6,500 people around the world since January Queensland researcher
claims HIV and anti-malaria drugs may be the cure Currently patients
cannot be cured and only supported while they recover Coronavirus
symptoms: what are they and should you see a doctor?
By BRITTANY CHAIN FOR DAILY MAIL AUSTRALIA And SAM BLANCHARD SENIOR
HEALTH REPORTER FOR MAILONLINE
PUBLISHED: 17:12 AEDT, 16 March 2020 | UPDATED: 18:15 AEDT, 17 March 2020
Drugs used to treat HIV and malaria could be used to tackle the
coronavirus, according to scientists in Australia.
A team of infectious disease experts at the University of Queensland in
Brisbane say they have seen two existing medications manage to wipe out
COVID-19 infections.
Chloroquine, an anti-malarial drug, and HIV-suppressing combination
lopinavir/ritonavir have both reportedly shown promising results in
human tests and made the virus 'disappear' in infected patients.
The drugs are being tested as researchers and doctors around the world
scramble to try and find a vaccine, cure or treatment for the deadly virus.
Around 170,000 people across the globe have now been infected with the
coronavirus and over 6,500 have died.
After China managed to get a handle on its sudden outbreak other
countries were blindsided by huge epidemics – almost 25,000 people have
caught it in Italy, around 14,000 in Iran, 8,000 in Spain and more than
5,000 apiece in Germany and France.
Queensland researcher, Professor David Paterson, said he hopes to enrol
people in larger scale pharmaceutical trials by the end of the month.
WHAT ARE THE DRUGS THAT COULD BE USED TO STOP THE CORONAVIRUS? CHLOROQUINE
Chloroquine is a drug which was once commonly used to prevent and treat
malaria.
As humans have developed an increased natural resistance to the
mosquito-borne disease, the drug has been used less frequently.
Researchers now believe it may hold the key to treating COVID-19, the
latest strain of coronavirus.
Common side affects include muscle problems, loss of appetite and diarrhoea.
In February 2020, Chinese medics determined the drug may be safe and
effective in treating coronavirus induced pneumonia.
LOPINAVIR/RITONAVIR (KALETRA)
The combined fixed dose drug has been used in the fight against HIV and
AIDS since 2006.
Some of the negative side affects to the drug include diarrhoea,
vomiting, feeling tired, headaches, and muscle aches.
Chinese medical researchers suggested the drug had successfully cured
coronavirus patients after the December 2019 outbreak.
Requests have been submitted in China to start a clinical trial of the
drug to accurately determine its effectiveness in fighting COVID-19.
Australian authorities are also hoping to test the drug on local patients.
Professor Paterson said it wouldn't be wrong to consider the drugs a
possible 'treatment or cure' for the deadly respiratory infection.
He explained that when the HIV medication lopinavir/ritonavir was given
to people infected with the coronavirus in Australia it led to the
'disappearance of the virus'.
He told Australian news site news.com.au: 'It's a potentially effective
treatment.
'Patients would end up with no viable coronavirus in their system at all
after the end of the therapy.'
Although the treatment had been effective in a smattering of cases,
there hasn't been any controlled testing like what would be needed to
test a new drug, Professor Paterson said.
'That first wave of Chinese patients we had (in Australia), they all did
very, very well when they were treated with the HIV drug,' Professor
Paterson said.
'What we want to do at the moment is a large clinical trial across
Australia, looking at 50 hospitals, and what we're going to compare is
one drug, versus another drug, versus the combination of the two drugs,'
Professor Paterson said.
There have been around 300 confirmed cases of the coronavirus in
Australia and three people have died.
Lopinavir/ritonavir, the anti-HIV drug being tested, is most commonly
sold under the name Kaletra.
It is an antiviral medication which can be taken twice a day by people
infected with HIV in order to reduce levels of the virus circulating in
the body.
Regular use of the medication is intended to stop HIV progressing to
AIDS, which is fatal, and may also reduce the risk of people
transmitting the infection to others.
It is a type of drug called a protease inhibitor, which works by
stopping viruses from using an enzyme called protease, which is vital
for them to be able to spread.
Without protease viruses cannot make the fully-matured clones that they
need to be able to infect other healthy cells, so the infection can't
spread.
This ability to stop a virus from reproducing and infecting new cells is
believed to be what apparently makes Kaletra an effective coronavirus
treatment.
More than 170,000 people around the world have been infected with the
coronavirus, and at least 6,512 have died.
{photo} The HIV drug Kaletra has shown promising results in the small
number of coronavirus patients who have been treated with it, scientists
say – they now want to start proper clinical trials
COULD AN EXPERIMENTAL EBOLA DRUG WORK?
Remdesivir, developed by California-based Gilead, has previously
protected animals against a variety of viruses in lab experiments.
The experimental drug has effectively treated monkeys infected with
Ebola and Nipah viruses, the US National Institutes of Health says.
At least two trials of the drug, originally developed as an Ebola
treatment, are known to be underway for SARS-CoV-2 in China.
Remdesivir works by blocking a protein that helps coronaviruses make
copies of themselves and, in turn, infect patients.
Scientists in China earlier this month filed a patent for remdesivir in
hope that it will help treat coronavirus patients.
More recently, remdesivir was found to help relieve symptoms in the
first American coronavirus patient while he was hospitalized.
It was given intravenously to a man in Washington, the very first person
diagnosed with coronavirus in the US, for compassionate use.
One day after he took the drug, he didn't need supplemental oxygen
anymore and his appetite improved. Four days later, his fever broke.
Kaletra is approved for use in the US, Europe and Australia, and its
manufacturer – AbbVie – has already donated supplies of the drug to
authorities China, the US and to the World Health Organisation. It is a
different combination to the PREP drug which was recently approved for
HIV prevention in the UK.
Chloroquine – an antimalarial drug – works in a different way and is
given to people to prevent malaria infections if they are bitten by a
mosquito carrying the parasite.
It does not cure malaria but stops it from developing when taken before,
during and after someone visits an at-risk area.
The drug works by salts inside them poisoning parasites and preventing
them from growing inside human red blood cells.
It has also been found to be able to destroy viruses, and scientists
found in lab tests that it could be effective against the coronavirus
(SARS-CoV-2).
Chloroquine is already widely used as an antimalarial for travellers and
is also approved in the UK for use on people with rheumatoid arthritis
or lupus.
Scientists are keen to use an already-approved medication to try and
treat the coronavirus because it would cut out the lengthy processes of
safety trials – they are already proven to be safe – and getting
government approval and manufacturing.
Professor Paterson, an infectious diseases physician, has launched a
fundraising appeal alongside the Royal Brisbane and Women's Hospital to
raise money to support the clinical trials.
The Coronavirus Action Fund hopes to raise $750,000 to go toward
understanding and better treating COVID-19.
A statement from the organisers says research and trials will be
underway as soon as funding is secured.
(5) FDA statement: no, these drugs are not approved as treatments for
COVID-19
Could the anti-malarial drug chloroquine treat COVID-19? By Nicoletta
Lanese - Staff Writer 20 March 2020
President Trump boasted the drug's promise, but it must still be put
through rigorous clinical trials.
Yesterday (March 19), President Donald Trump boasted about the "very
encouraging results" of two drugs called chloroquine and
hydroxychloroquine as treatments for the novel coronavirus, claiming
that the medications have "gone through the approval process" and that
"we're going to be able to make that drug available almost immediately."
But the U.S. Food and Drug Administration (FDA) swiftly issued a
statement to clarify that, no, these drugs are not approved as
treatments for COVID-19, the disease caused by the coronavirus
SARS-CoV-2. Both drugs are approved to treat malaria, lupus and
rheumatoid arthritis, but must still be assessed in clinical trials
before being declared a safe and effective COVID-19 treatment. Doctors
in the U.S. have wide latitude to prescribe drugs "off-label," meaning
for conditions beyond their initial FDA approval.
"We understand and recognize the urgency with which we are all seeking
prevention and treatment options for COVID-19. FDA staff are working
expeditiously on that front," FDA commissioner Dr. Stephen M. Hahn said
in the statement. "We also must ensure these products are effective;
otherwise we risk treating patients with a product that might not work
when they could have pursued other, more appropriate, treatments." [...]
The science behind chloroquine First developed in the 1940s, chloroquine
earned FDA approval as a malaria treatment in 1949 and long stood as the
go-to treatment for the disease, according to the DrugBank database.
A 2005 report published in the journal Virology first raised the
possibility that chloroquine and its derivative hydroxychloroquine might
be effective at treating COVID-19, Dr. Len Horovitz, an internist and
pulmonary specialist at Lenox Hill Hospital in New York City, told Live
Science. The study revealed that chloroquine could prevent the spread of
the SARS-CoV virus, which caused severe acute respiratory syndrome
nearly 20 years ago, in primate cells grown in culture.
Chloroquine interferes with the virus's ability to replicate in two
ways. First, the drug enters compartments called endosomes within the
cell membrane. Endosomes tend to be slightly acidic, but the chemical
structure of the drug boosts their pH, making the compartments more
basic. Many viruses, including SARS-CoV, acidify endosomes in order to
breach the cell membrane, release their genetic material and begin
replication; chloroquine blocks this critical step.
The drug also prevents SARS-CoV from plugging into a receptor called
angiotensin-converting enzyme 2, or ACE2, on primate cells, according to
the 2005 report. When the virus inserts its spike protein into the ACE2
receptor, it sets off a chemical process that alters the structure of
the receptor and allows the virus to infect. An adequate dose of
chloroquine appears to undermine this process, and in turn, viral
replication in general, the authors noted.
"It was thought that whatever pertained to SAR-CoV-1 might apply to
SARS-CoV-2," Horovitz said.
Related: 11 deadly diseases that hopped across species
Could it work? In February, a research group led by virologist Manli
Wang of the Chinese Academy of Sciences put the idea to the test and
found that chloroquine successfully stopped the spread of SARS-CoV-2 in
cultured human cells. Preliminary reports from China, South Korea and
France suggest that the treatment is at least somewhat effective in
treating human patients, and some hospitals in the U.S. have begun
administering the drug, according to The New York Times. In addition,
the FDA is organizing a large clinical trial to formally assess the
drug's effects, the Times reported.
However, due to a short supply of chloroquine in China, and the fact
that an overdose can lead to acute poisoning or death in humans, Wang's
team also investigated the closely related drug hydroxychloroquine.
Though it shares a similar structure, hydroxychloroquine shows lower
toxicity in animals than its chemical cousin and remains widely
available as a treatment for lupus and rheumatoid arthritis, the authors
noted.
Wang's team tested hydroxychloroquine in primate cells and found that,
like chloroquine, the drug prevented SARS-CoV-2 replication, according
to a report published March 18 in the journal Cell Discovery. As of Feb.
23, seven clinical trials had been registered in the Chinese Clinical
Trial Registry to test the drug's effectiveness against COVID-19
infection, the authors noted.
In the U.S., the University of Minnesota is studying whether taking
hydroxychloroquine can protect people living with infected COVID-19
patients from catching the virus themselves, according to the Times.
Both chloroquine and hydroxychloroquine have been in short supply since
earlier this month, according to the American Society of Health-System
Pharmacists. But on March 19, the pharmaceutical company Bayer donated 3
million tablets to the federal government, and Novartis, Mylan and Teva
are moving to follow suit, according to FiercePharma.
Although we won't know the results of these trials for some time, the
advantage of trying out chloroquine and hydroxychloroquine as COVID-19
treatments is that the drugs' safety profiles are well understood,
Horovitz said. Both drugs are generally well tolerated at prescribed
doses but can cause stomach pain, nausea, vomiting, headache and more
rarely, itchiness, according to the Centers for Disease Control and
Prevention (CDC). When taken in high doses over many years, the drugs
can cause a rare eye condition known as retinopathy.
Both medications can interact with other drugs and doses should be
adjusted to account for drug interactions. Those with psoriasis should
not take either drug, the CDC notes. In their current form, the drugs
are also not safe for those with heart arrhythmia, or those with
impaired kidneys or liver, the Times reported.
Assuming the drugs are well tolerated in clinical trials and seem
effective at treating COVID-19, the FDA will take measures to increase
the nation's supply, according to Hahn.
"If clinical data suggests this product may be promising in treating
COVID-19, we know there will be increased demand for it," Hahn said in
the FDA statement. "We will take all steps to ensure chloroquine remains
available for patients who take it to treat severe and life-threatening
illnesses such as lupus."
(6) Is it ok to use a drug that's not yet certified? Bureaucrats Fiddle
while Rome burns
Hydroxychloroquine, chloroquine and other potential COVID-19 treatments
explained
Darrell Etherington@etherington / 5:37 am AEST o March 21, 2020
During two of this week's White House briefings, President Trump
referred specifically to two potential treatments that have been
identified by medical researchers and clinicians, and that have
undergone various degrees of investigation and testing in the ongoing
fight against the global coronavirus pandemic. It's important to note
upfront that regardless of what you may have heard, from Trump or any
other sources, no drugs or treatments have been proven as effective for
either the prevention of contracting COVID-19 or for its treatment.
That said, a number of different clinical studies are currently in
progress all over the world, and in the U.S., the National Institutes of
Health is looking to fill a 400-volunteer study that will provide
clinical results related to use of remdesivir, an antiviral drug
developed by Gilead originally as a treatment for Ebola, but it's still
only in clinical trials even for treatment of that disease. This study
could also add other drug candidates as additional test therapies.
Meanwhile, studies in China and France have examined the effectiveness
of anti-malarial drugs, including chloroquine and hydroxychloroquine —
including one small-scale study that suggests the positive effects of
hydroxycholoroquine in reducing both the duration and symptoms of
COVID-19 in combination with an antibiotic called azithromycin.
The important thing to keep in mind when considering these or any other
potential treatments for the novel coronavirus, which is still
relatively young, is that a lot of what we know about them so far is
effectively anecdotal, and based not on the kind of scientifically
rigorous controlled clinical studies that are normally used in the
years-long development and certification of drugs. Instead, treatments
like remdesivir and chloroquine/hydroxychloroquine
the field by healthcare practitioners based on their approved use in
similar (but crucially not the same) situations, like the Ebola and SARS
outbreaks.
Often, they're being used under what's called "compassionate" grounds in
the U.S. This effectively amounts to employing a drug that's not yet
certified for general use in treatment of a patient whose condition is
so severe that a doctor is willing to go to desperate lengths to try to
alleviate their symptoms. This has the advantage of sidestepping typical
testing and approval procedures, and requiring that the results of its
use are documented, which contributes to the overall body of clinical
knowledge in terms of its effects and interactions with patients and
with COVID-19.
It's not a clinical study, however, and that means there are still a lot
of unknowns when it comes to its use that just can't be learned or
asserted based on scattered, individual instances of compassionate care
treatment.
"As the Commissioner of FDA and the president mentioned yesterday, we're
trying to strike a balance between making something with the potential
of an effect available to the American people, at the same time that we
do it under the auspices of a protocol that would give us information to
determine if it's truly safe and truly effective," explained National
Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci
during a press conference on Friday. "But the information that you're
referring to specifically is anecdotal, it was not done in a controlled
clinical trial. So you really can't make any definitive statement about it."
During Thursday's White House coronavirus pandemic task force briefing,
Trump made false claims that chloroquine was already approved by the FDA
as a treatment for COVID-19 under an emergency authorization. FDA
Director Dr. Stephen Hahn clarified that this and remdesivir were being
considered and studied by the FDA, as was an approach that would use
plasma extracted from patients who'd recovered from COVID-19, as a
potential source of antibodies for others. Still, all of these are still
quite far away from clinical deployment in any generally approved way.
Meanwhile, Fauci's cautions should be taken for what they are: Warnings
that are primarily meant to emphasize that the reason the FDA requires
clinical studies, even for drugs already tentatively approved for use in
other cases, is because it has patient health and safety in mind. While
chloroquine has been used for decades to treat malaria, and chronic
rheumatoid arthritis, it can have dangerous side effects, including
death, if taken incorrectly. Even when taken correctly, it can cause
things like stomach distress, and even permanent damage to a person's
vision.
Fauci's comments Friday explain the risks of putting too much stock in
any potential treatment at this stage, even if they are showing
promising results among small or even medium-sized deployments.
"You've got to be careful when you say 'fairly effective,' it was never
done in a clinical trial that compared it to anything," he said in
answer to a reporter's question about chloroquine's efficacy in treating
SARS. "It was given to individuals and felt that maybe it worked […]
Whenever you do a clinical trial, you do standard of care, versus
standard of care plus the agent you're evaluating. That's the reason why
we showed back in Ebola why particular interventions worked."
A summary survey of various prospective treatments and their current
status was published today In Medscape, and this includes the current
state of remdesivir and chloroquine investigations, as well as a number
of other drugs being studied by researchers. As has been reported here
and elsewhere, there are promising signs that they could prove effective
in either treatment, or treatment and even preventative use (in the case
of remedesivir), but these are, as Dr. Fauci puts it, only the first
step that should lead to more sophisticated clinical studies, which
themselves will then need competing peer studies to eventually prove out.
(7) Hydroxychloroquine (HCQ) less effective than Chloroquine (CQ) in
inhibiting SARS-CoV-2; thanks to Zhengli Shi
Published: 18 March 2020
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective
in inhibiting SARS-CoV-2 infection in vitro
Jia Liu, Ruiyuan Cao, Mingyue Xu, Xi Wang, Huanyu Zhang, Hengrui Hu,
Yufeng Li, Zhihong Hu, Wu Zhong & Manli Wang
Cell Discovery volume 6, Article number: 16 (2020) Cite this article
Dear Editor,
The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) poses a
serious threat to global public health and local economies. As of March
3, 2020, over 80,000 cases have been confirmed in China, including 2946
deaths as well as over 10,566 confirmed cases in 72 other countries.
Such huge numbers of infected and dead people call for an urgent demand
of effective, available, and affordable drugs to control and diminish
the epidemic.
We have recently reported that two drugs, remdesivir (GS-5734) and
chloroquine (CQ) phosphate, efficiently inhibited SARS-CoV-2 infection
in vitro1. Remdesivir is a nucleoside analog prodrug developed by Gilead
Sciences (USA). A recent case report showed that treatment with
remdesivir improved the clinical condition of the first patient infected
by SARS-CoV-2 in the United States2, and a phase III clinical trial of
remdesivir against SARS-CoV-2 was launched in Wuhan on February 4, 2020.
However, as an experimental drug, remdesivir is not expected to be
largely available for treating a very large number of patients in a
timely manner. Therefore, of the two potential drugs, CQ appears to be
the drug of choice for large-scale use due to its availability, proven
safety record, and a relatively low cost. In light of the preliminary
clinical data, CQ has been added to the list of trial drugs in the
Guidelines for the Diagnosis and Treatment of COVID-19 (sixth edition)
published by National Health Commission of the People's Republic of
China. [...]
Whether HCQ is as efficacious as CQ in treating SARS-CoV-2 infection
still lacks the experimental evidence.
To this end, we evaluated the antiviral effect of HCQ against SARS-CoV-2
infection in comparison to CQ in vitro. [...] Taken together, the data
suggest that the anti-SARS-CoV-2 activity of HCQ seems to be less potent
compared to CQ, at least at certain MOIs. [...]
It has been reported that oral absorption of CQ and HCQ in humans is
very efficient. In animals, both drugs share similar tissue distribution
patterns, with high concentrations in the liver, spleen, kidney, and
lung reaching levels of 200–700 times higher than those in the plasma10.
It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate
could generate serum levels of 1.4–1.5 mM in humans11. Therefore, with a
safe dosage, HCQ concentration in the above tissues is likely to be
achieved to inhibit SARS-CoV-2 infection.
Clinical investigation found that high concentration of cytokines were
detected in the plasma of critically ill patients infected with
SARS-CoV-2, suggesting that cytokine storm was associated with disease
severity12. Other than its direct antiviral activity, HCQ is a safe and
successful anti-inflammatory agent that has been used extensively in
autoimmune diseases and can significantly decrease the production of
cytokines and, in particular, pro-inflammatory factors. Therefore, in
COVID-19 patients, HCQ may also contribute to attenuating the
inflammatory response. In conclusion, our results show that HCQ can
efficiently inhibit SARS-CoV-2 infection in vitro. In combination with
its anti-inflammatory function, we predict that the drug has a good
potential to combat the disease. This possibility awaits confirmation by
clinical trials. We need to point out, although HCQ is less toxic than
CQ, prolonged and overdose usage can still cause poisoning. And the
relatively low SI of HCQ requires careful designing and conducting of
clinical trials to achieve efficient and safe control of the SARS-CoV-2
infection.
References
1. Wang, M. et al. Remdesivir and chloroquine effectively inhibit the
recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30,
269–271 (2020).
2. Holshue, M. L. et al. First case of 2019 novel coronavirus in the
United States. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2001191
(2020).
3. Weniger, H. Review of side effects and toxicity of chloroquine. Bull.
World Health 79, 906 (1979).
4. McChesney, E. W. Animal toxicity and pharmacokinetics of
hydroxychloroquine sulfate. Am. J. Med. 75, 11–18 (1983).
5. Mauthe, M. et al. Chloroquine inhibits autophagic flux by decreasing
autophagosome-lysosome fusion. Autophagy 14, 1435–1455 (2018).
6. Savarino, A. et al. New insights into the antiviral effects of
chloroquine. Lancet Infect. Dis. 6, 67–69 (2006).
7. Mingo, R. M. et al. Ebola virus and severe acute respiratory syndrome
coronavirus display late cell entry kinetics: evidence that transport to
NPC1+ endolysosomes is a rate-defining step. J. Virol. 89, 2931–2943 (2015).
8. Zheng, N., Zhang, X. & Rosania, G. R. Effect of phospholipidosis on
the cellular pharmacokinetics of chloroquine. J. Pharmacol. Exp. Ther.
336, 661–671 (2011).
9. Ohkuma, S. & Poole, B. Fluorescence probe measurement of the
intralysosomal pH in living cells and the perturbation of pH by various
agents. Proc. Natl Acad. Sci. USA 75, 3327–3331 (1978).
10. Popert, A. J. Choloroquine: a review. Rheumatology 15, 235–238 (1976).
11. Laaksonen, A. L., Koskiahde, V. & Juva, K. Dosage of antimalarial
drugs for children with juvenile rheumatoid arthritis and systemic lupus
erythematosus. A clinical study with determination of serum
concentrations of chloroquine and hydroxychloroquine. Scand. J.
rheumatol. 3, 103–108 (1974).
12. Huang, C. et al. Clinical features of patients infected with 2019
novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).
Download references
Acknowledgements
We thank Professor Zhengli Shi and Dr. Xinglou Yang from Wuhan Institute
of Virology and Professor Fei Deng from National Virus Resource Center
for providing SARS-CoV-2 strain (
Professor Xiulian Sun for kind help in statistical analysis; Professor
Zhenhua Zheng for kindly providing the anti-LAMP1 rabbit polyclonal
antibody; Prof. Zhengli Shi for kindly providing the anti-NP polyclonal
antibody; Beijing Savant Biotechnology Co., ltd for kindly providing the
anti-NP monoclonal antibody; Min Zhou and Xijia Liu for their assistance
with this study; Jia Wu, Jun Liu, Hao Tang, and Tao Du from BSL-3
Laboratory and Dr. Ding Gao from the core faculty of Wuhan Institute of
Virology for their critical support; Professor Gengfu Xiao, Professor
Yanyi Wang and other colleagues of Wuhan Institute of Virology and Wuhan
National Biosafety Laboratory for their excellent coordination; and Dr.
Basil Arif for scientific editing of the manuscript. This work was
supported in part by grants from the National Science and Technology
Major Projects for "Major New Drugs Innovation and Development"
(2018ZX09711003 to W.Z.), the National Natural Science Foundation of
China (31621061 to Z.H.), and the Hubei Science and Technology Project
(2020FCA003 to Z.H.).
Author information
Author notes
These authors contributed equally: Jia Liu, Ruiyuan Cao, Mingyue Xu
Affiliations
State Key Laboratory of Virology, Wuhan Institute of Virology, Center
for Biosafety Mega-Science, Chinese Academy of Sciences, 430071, Wuhan,
China
Jia Liu, Mingyue Xu, Xi Wang, Huanyu Zhang, Hengrui Hu, Yufeng Li,
Zhihong Hu & Manli Wang
National Engineering Research Center for the Emergency Drug, Beijing
Institute of Pharmacology and Toxicology, 100850, Beijing, China
Ruiyuan Cao & Wu Zhong
University of the Chinese Academy of Sciences, 100049, Beijing, China
Mingyue Xu, Huanyu Zhang, Hengrui Hu & Yufeng Li
Contributions
Z.H., M.W., and W.Z. conceived and designed the experiments and provided
the final approval of the manuscript. J.L., R.C., M.X., X.W., H.Z.,
H.H., and Y.L. participated in multiple experiments; all the authors
analyzed the data. M.W., R.C., J.L., and Z.H. wrote the manuscript.
Corresponding authors
Correspondence to Zhihong Hu or Wu Zhong or Manli Wang.
(8) Hospitals are not waiting for the FDA bureaucrats: Chloroquine in
short supply as hospitals buy in bulk
March 20, 2020 05:05 PM
Chloroquine in short supply as hospitals buy in bulk
While the U.S. Food and Drug Administration is still investigating
whether the inexpensive, old anti-malaria drugs can tame symptoms and
limit the spread of the highly contagious virus, hospitals have
responded to clinical trials in other countries that have shown
promising results.
Orders of chloroquine spiked 3,000% in March, according to data from
Premier, the group purchasing and consulting organization. From January
2019 through February 2020, hospitals ordered an average of 149 units a
month. More than 2,300 units were ordered through March thus far.
Its variant hydroxychloroquine experienced a 260% surge in demand,
Premier data show. Hospitals typically used about 8,800 units a month,
jumping to 16,110 units ordered in March.
Chloroquine phosphate tables and hydroxychloroquine sulfate tablets went
into shortage on March 9 and March 19, respectively, according to the
American Society of Health System Pharmacists.
All major wholesale distributors put hydroxychloroquine and chloroquine
on allocation this week, which limits ordering to prevent hoarding,
Premier said.
"As additional reports come forth from countries suggesting treatment
protocols for COVID-19, a single source of truth in the U.S. is needed
to mitigate panic-buying," Premier said in the report. The Centers for
Disease Control and Prevention should study the international data and
make recommendations for treatment protocols domestically, Premier offered.
Chloroquine, which is also used to treat lupus and rheumatoid arthritis,
isn't typically well stocked by hospitals, if at all, said Erin Fox, a
drug shortage expert and senior director of drug information and support
services at University of Utah Health.
"It's more of a travel medicine to be used for malaria treatment," said
Fox, adding that University of Utah Health bought a small amount at the
end of February to have on hand just in case when it saw some
preliminary data from China. "We don't have a lot of malaria in the U.S.
— probably why it was fine for just one company to supply the entire U.S."
While a single manufacturer produces chloroquine, four additional
manufacturers are approved by the FDA to make it, Premier noted. There
are 10 suppliers with FDA approval to produce hydroxychloroquine, but
not all of them are currently manufacturing.
Some of the manufacturers of chloroquine and related products have
lowered prices and donated millions of doses to the U.S. government.
Last month, the National Institutes of Health began a randomized
controlled trial for the treatment of COVID-19 patients with Gilead
Sciences' antiviral drug remdesivir. It is one of several drugs that are
being tested for COVID-19 treatment, but quality and pricing questions
remain.
"We understand and recognize the urgency with which we are all seeking
prevention and treatment options for COVID-19. FDA staff are working
expeditiously on that front," FDA Commissioner Dr. Stephen Hahn, said in
prepared remarks. "We also must ensure these products are effective;
otherwise we risk treating patients with a product that might not work
when they could have pursued other, more appropriate, treatments."
The drug supply chain is already working around restricted access to
pharmaceutical ingredients. The Indian government is limiting the export
of 26 ingredients, some of which are used in widely used antibiotics, to
protect its domestic supply amid the pandemic.
Much of the world's supply of generic drugs comes from India, which
relies heavily on China for their active pharmaceutical ingredients.
(9) Military personnel given Flu vaccine were significantly more
susceptible to Coronavirus
This most important result is buiried amidst platitudes. I have cut away
the platitudes so that you can see the important bits - Peter M.
2020 Study Shows Common Flu Shots Make Recipients More Susceptible To
Coronavirus Lung Infections
MARCH 20, 2020
By CFT TEAM
A 2020 study conducted by the U.S. Department of Defense entitled,
Influenza vaccination and respiratory virus interference among
Department of Defense personnel during the 2017–2018 influenza season by
Greg G. Wolff, published in Vaccine, Volume 38, Issue 2, 10 January
2020, Pages 350-354, found that military personnel who had received
seasonal flu shots were significantly more susceptible to
coronavirus-associated respiratory infections:
Purpose
Receiving influenza vaccination may increase the risk of other
respiratory viruses, a phenomenon known as virus interference.
Test-negative study designs are often utilized to calculate influenza
vaccine effectiveness. The virus interference phenomenon goes against
the basic assumption of the test-negative vaccine effectiveness study
that vaccination does not change the risk of infection with other
respiratory illness, thus potentially biasing vaccine effectiveness
results in the positive direction. This study aimed to investigate virus
interference by comparing respiratory virus status among Department of
Defense personnel based on their influenza vaccination status.
Furthermore, individual respiratory viruses and their association with
influenza vaccination were examined.
Results
We compared vaccination status of 2880 people with non-influenza
respiratory viruses to 3240 people with pan-negative results. Comparing
vaccinated to non-vaccinated patients, the adjusted odds ratio for
non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09;
p?=?0.60). Additionally, the vaccination status of 3349 cases of
influenza were compared to three different control groups: all controls
(N?=?6120), non-influenza positive controls (N?=?2880), and pan-negative
controls (N?=?3240). The adjusted ORs for the comparisons among the
three control groups did not vary much (range: 0.46–0.51).
Conclusions
Receipt of influenza vaccination was not associated with virus
interference among our population. Examining virus interference by
specific respiratory viruses showed mixed results. Vaccine derived virus
interference was significantly associated with coronavirus and human
metapneumovirus; however, significant protection with vaccination was
associated not only with most influenza viruses, but also parainfluenza,
RSV, and non-influenza virus coinfections.
The average age of patients in Italy who have died of COVID-19 infection
is 81, most of whom already had other underlying medical conditions.
A whopping 70% of seniors in the U.S. get their annual flu shots, much
higher than the general population, and many of them are receiving ‘high
dose’ versions of the vaccine.
According to the manufacturers’ package inserts that come with these
vaccines, one of the known and not-so-uncommon side effects of these
vaccines is stroke in the elderly.
And now we find out that these heavily-promoted seasonal flu shots are
making everyone, including the vulnerable elderly, significantly more
susceptible to potentially fatal coronavirus lung infections.
Despite these facts, we can expect that during this coronavirus ‘event’,
the CDC will promote seasonal flu shots with even greater urgency.
And despite researchers knowing that two common and inexpensive
medications can ‘cure’ coronavirus infections, the CDC and hospitals
seem to be acting as if these drugs don’t exist, opting to let these
COVID-19 patients die while waiting for another ineffective experimental
vaccine to hit the market.
The elderly are the greatest expense to the Federal health care budget,
so what better way to cut costs than to cull the herd under the fog of
this overblown ‘pandemic’?
Volume 38, Issue 2, 10 January 2020, Pages 350-354
Influenza vaccination and respiratory virus interference among
Department of Defense personnel during the 2017–2018 influenza season
Greg G.Wolff
https://doi.org/10.1016/j.vaccine.2019.10.005Get rights and content
Highlights o We examined virus interference in a Department of Defense
dependent population.
o Vaccinated personnel did not have significant odds of respiratory
illnesses.
o Vaccinated personnel were protected against influenza.
o Odds of virus interference by vaccination varied for individual
respiratory viruses.
[...] 4. Discussion
[...] Additionally, the laboratory data in our study showed increased
odds of coronavirus and human metapneumovirus in individuals receiving
influenza vaccination. The study finding similar results to our study
found no association between influenza vaccination and RSV, adenovirus,
human metapneumovirus, rhinovirus or coronavirus [12]. The same study
did find a significant association between parainfluenza and influenza
vaccination, but the association was in opposite directions when
comparing children and adults [12]. In our disease specific
investigation, virus interference trends were noticed for coronavirus
and human metapneumovirus [...]
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