Coronavirus treatment options and the impact on public policy

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We started this around the first of april and treatments are being rolled out now, even while we await final results from the clinical trials.
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Canada begins clinical trial of experimental COVID-19 treatment using plasma from recovered individuals

Approach previously tested in small trials transfers antibodies to help fight illness

www.theglobeandmail.com

A team of blood transfusion experts from across Canada is planning the world’s largest clinical trial of a potential treatment for COVID-19.
MICHAEL DOYLE
PUBLISHED APRIL 6, 2020

The study, which will involve 1,000 patients from across the country, will include at least 40 Canadian hospitals, and is being overseen by doctors from the University of Montreal, University of Ottawa, University of Toronto, McMaster and the University of British Columbia, among other schools.

The experimental treatment involves injecting antibody-rich plasma from patients who have recovered from the virus into those who are still infected. This approach has only been tried in small trials in China, Singapore, South Korea and the U.S. It is part of a global race to find a treatment for the disease, with researchers also focusing on antivirals and medications used to treat malaria.

Donation centres across Canada will extract plasma, a straw-yellow liquid component of blood, from recovered patients and test that it has a certain minimum number of antibodies to be considered useful as an immunotherapy. Known as convalescent plasma, the material will then be frozen, sent to participating hospitals and infused into a critical patient to see if it can help treat their illness. In the early stages of infection, the body doesn’t produce the antibodies needed to fight off the novel coronavirus, according to Dr. Donald Arnold, a hematologist at McMaster University who is leading the trial.

“The theory is that people who have recovered from COVID infection may have antibodies to fight the virus,” Dr. Arnold said.

Canada’s two blood suppliers, Canadian Blood Services and Héma-Québec, will be managing donations from those who have fully recovered from COVID-19.

Late last month, a small Chinese study of five ventilated patients suggested the technique could be used to temper the severity of coronavirus. Three of the five patients were able to be weaned off ventilators days after receiving plasma. During the SARS outbreak, 80 patients were treated with convalescent plasma. A review of that study showed that the earlier the transfusion, the better the outcome of the patient. None of the patients in that trial experienced adverse reactions to the treatment.

In late March, U.S. regulators allowed doctors to begin collecting recovered patients’ plasma for emergency use. Dr. Arnold, the lead of the Canadian trial, admits that the treatment is a “Hail Mary.” While transfusion therapies aren’t typically risky for the patient, there is a chance this trial won’t have a significant impact in treating COVID-19, instead draining resources and time.

Dr. Michael Joyner of the Mayo Clinic, which will run the American national supply chain of plasma, said on Wednesday that their findings will be shared with other countries in virtual real time.

The plan for the Canadian trial came together in just days. A group of a dozen hematologists and scientists joined a Zoom call on March 29 and worked out a plan – a process that usually takes between six months and a year for a typical trial, according to Dr. Arnold.

The researchers soon learned that a parallel trial was being developed in Quebec. The following day, they merged into one large unit, with different participating institutions tackling potential subdivisions of research. Dr. Arnold said that by April 1, nearly every hospital in the country treating COVID-19 patients had signed on to participate.

Dr. Dana Devine, Canadian Blood Services’ head scientist, said that while China is now collecting donations from multiple sites, there hasn’t yet been a large patient study with a control group – meaning that certain patients don’t receive plasma – which is the gold standard for clinical trials and would be key in determining the widespread efficacy of this treatment.

She said that the group is now finalizing funding and infrastructure while Canada’s two blood banks work with provincial health ministries to contact all recovered positive COVID-19 cases about donating.

Donating plasma is no different than conventional blood donation, according to Dr. Devine, and takes about 45 minutes. She said each donor’s plasma will be studied for its virus-fighting viability.

All patients who are hospitalized and need oxygen will be able to sign up for the trial.

“It’s a flip of a coin – two-thirds of patients will get the antibody-rich blood, with the other third being a control group,” Dr. Arnold said. The control group would receive standard care.

The trial could be completed in as little as three months. Dr. Arnold said they are realistically looking at six to 10 months before they have definitive results.

“The challenge is to get to an answer as quickly as possible so that we can start using this product if it’s truly effective, or realize it’s not and stop using it,” Dr. Arnold said.

Dr. Rulan Parekh of SickKids Hospital in Toronto said there will also be a pediatric component to the trial, and that there will be multiple concurrent studies, including those to determine longer-term immunotherapies.

“I’ll be doing a larger study, with Dr. Devine, of donors to understand their immunity,” she said. “We also hope to get viable candidates to help create a large repository, so scientists can use their blood to think about immunotherapies.” Those could include a treatment that could help protect front-line medical workers who have significantly greater chance of infection.

Richard Carl, who recovered from COVID-19 after contracting it while on a ski trip in Colorado in February, said he will be a donor.

Mr. Carl did not require hospitalization, but was treated at Sunnybrook Hospital in Toronto. He was cleared of the virus on March 25, and as this study came together last week, he was nominated to its advisory board as the patient representative.


“There is a real feeling of helplessness in the world today,” Mr. Carl said from his home in Toronto. “The thought of asking someone to help fix this thing – I couldn’t say yes fast enough.”

Mr. Carl said he hopes others who have recovered from the virus will come out in larger numbers to donate plasma.

“We’re going to need blood, and those who have been infected, like me, need to join us in this,” he said. “We need to help fight this, and also help these front-line health-care workers – they are putting themselves in harm’s way to save lives.”

Using convalescent plasma to battle a virus isn’t a new discovery, Dr. Arnold said, adding doctors first discovered this therapy at the end of the 1918-19 Spanish flu pandemic.

“There’s nothing 21st century about this – this is so old school,” he said.

 

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"Elite" antibodies from COVID-19 survivors point to novel treatment

As researchers rekindle a more than 100-year-old therapy, using blood from recovered COVID-19 subjects as a treatment for newly infected patients, a team from the Rockefeller University Hospital in New York is thrusting this old, experimental treatment into the 21st century. The research is hunting…

newatlas.com

"Elite" antibodies from COVID-19 survivors point to novel treatment

As researchers rekindle a more than 100-year-old therapy, using blood from recovered COVID-19 subjects as a treatment for newly infected patients, a team from the Rockefeller University Hospital in New York is thrusting this old, experimental treatment into the 21st century. The research is hunting for "elite" antibodies in the blood of recovered patients, with the aim of cloning the most potent antibodies and mass produce a COVID-19 treatment.
more...

 

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Treating Covid-19 with 'Convalescent Plasma Therapy' | ANC

The stakes are high with global leaders wanting to get first dibs as the race for a Covid-19 vaccine intensifies. IG Biotech looks to find a treatment for the disease through Convalescent Plasma Therapy, or the use of anti-bodies found in the blood of survivors to help those still battling Covid.

 

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Exclusive: Bangladesh's Beximco to begin producing COVID-19 drug remdesivir - COO

One of Bangladesh's largest drugmakers, Beximco Pharmaceuticals, will start production this month of the experimental antiviral drug remdesivir, which has shown promise in fighting the new coronavirus, a senior company executive said on Tuesday.

www.reuters.com

Exclusive: Bangladesh's Beximco to begin producing COVID-19 drug remdesivir - COO

NEW DELHI (Reuters) - One of Bangladesh’s largest drugmakers, Beximco Pharmaceuticals, will start production this month of the experimental antiviral drug remdesivir, which has shown promise in fighting the new coronavirus, a senior company executive said on Tuesday.

Remdesivir, a drug developed by Gilead Sciences, has grabbed attention as one of the most promising treatments for COVID-19, the respiratory disease caused by the novel coronavirus that has killed more than 250,000 people.

U.S. drug authorities granted emergency use authorisation last week, paving the way for its broader use in U.S. hospitals, after Gilead provided data showing the drug had helped COVID-19 patients.

The company plans to price the drug, which is given via intravenous infusion, at between 5,000 and 6,000 takas per vial ($59-$71/per vial), Beximco’s Chief Operating Officer Rabbur Reza told Reuters, adding a patient might need anywhere between 5 and 11 vials.

“We will only know exactly how much a patient needs once studies are complete,” Reza said. “We do expect the Bangladesh government will try to cover some of the price of the drug.”

Production will begin this month, initially for domestic use, Reza added.

Beximco’s pricing indicates a course of remdesivir treatment could cost between $295 and $781 per patient in the south Asian country depending on the severity of the case, the number of vials required and the final pricing of the drug.

The figures are a first indication of how the drug will be priced, as countries around the world struggle to control the coronavirus that has infected more than 3.5 million people worldwide.

Gilead has donated an initial batch of 1.5 million vials of to help patients in the United States, but has yet to announce its pricing.

The Institute for Clinical and Economic Review (ICER), which assesses the effectiveness of drugs to determine appropriate prices, put the cost of producing a 10-day course of remdesivir at $10, but suggested the price could rise to $4,500 based on patient benefits shown in clinical trials.

AFFORDABILITY WAIVER
Gilead’s patent on remdesivir in theory means it has exclusive rights to make it, but international trade rules allow nations defined by the United Nations as least-developed countries, including Bangladesh, to ignore such patents and make drugs more affordable in those markets.

Bangladesh would be allowed to export the drug to other least-developed countries and some European countries have also written to Beximco seeking to import the drug, said Reza, declining to name the countries.

“We can seek approval from the government to export it for emergencies,” he said. “But we should be able to supply to our people first, that is number one for us.”

Bangladesh has so far reported 10,929 cases and 183 deaths from the disease, although some experts say the number of cases could be much higher given limited testing in the country.

WILL IT WORK?
Remdesivir was previously developed to treat the Ebola virus and did not work.

Its potential to help COVID-19 patients is based on ability to disable the mechanism by which certain viruses, including the new coronavirus, replicate themselves and potentially overwhelm their host’s immune system.

Data from a trial by the National Institutes of Health (NIH) in the United States showed remdesivir reduced hospitalisation stays by 31% compared to a placebo treatment, but did not significantly improve survival.

Beximco expects to receive marketing approval for remdesivir from Bangladesh authorities by mid-May, following which it plans to launch commercial quantities to be distributed via the government, Reza told Reuters.

“We’ll produce the drug depending on how much the Bangladesh government requires,” he said, adding officials were checking on quantities required by domestic hospitals.

Reza said a Chinese firm was providing the active pharmaceutical ingredients needed to make the drug. That supply deal would allow it to make up to 100,000 units of the drug, he said.

Based in Dhaka, Beximco Pharma exports generic drugs to some 50 countries from the United States to South Africa and makes everything from plain generic drugs to complex molecules.

Seven other Bangladeshi pharma companies including Square Pharmaceuticals and Beacon Pharmaceutical have received government approval to develop the drug, Bangladeshi drug regulatory official Mohammad Salahuddin said.

“For now, we won’t allow the companies to export remdesivir. First, they’ll have to fulfil local demand, then we can consider it,” he told Reuters.

In neighbouring India, drugmaker Cipla Ltd said it was also working on three antivirals, including favipiravir, remdesivir and bolaxavir, which could be used to treat COVID-19. It declined to comment on its launch or pricing plans.

 

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Drug inspired by an old treatment could be the 'next big thing for Covid-19' | CNN

At least five US teams have cloned antibodies to Covid-19, paving the way for cutting-edge treatments that could be what one researcher calls "an immunity bridge" before a vaccine comes along.

www.cnn.com

Drug inspired by an old treatment could be the 'next big thing for Covid-19'

(CNN)At least five US teams have cloned antibodies to Covid-19, paving the way for cutting-edge treatments that could be what one researcher calls "an immunity bridge" before a vaccine comes along.
The treatment is monoclonal antibody therapy, and the antibodies come from people who have recovered from the novel coronavirus. Researchers then take the blood, select the most potent antibodies, and make them into a drug.
One company, Regeneron Pharmaceuticals, hopes to have a treatment available to patients as early as the end of the summer.
"I think monoclonal antibody therapy has enormous promise as the next big thing for Covid-19," said Dr. Peter Hotez, a vaccine specialist at Baylor University School of Medicine who is not involved in the research.


Monoclonal antibody therapy is a modern take on convalescent plasma, where someone who has recovered from coronavirus donates blood to someone who is currently ill.
Even if convalescent plasma is effective -- it's still being studied -- it has two shortcomings.
First, one person can only give so much blood. Second, the donor might not have enough strong antibodies for the blood donation to be effective.
To develop a monoclonal antibody treatment, researchers cull through thousands of antibodies to find the best ones, and then clone them potentially in unlimited amounts.
Many other illnesses are treated with monoclonal antibodies, such as various forms of cancer, HIV, asthma, lupus, multiple sclerosis and various forms of cancer, but of course there's no guarantee it could work for Covid-19.

"One of the things about the search is it's a little bit like finding a needle in a haystack. We're all searching for the magical antibody that's a silver bullet," said Dr. James Crowe, who's leading the Covid-19 monoclonal antibody effort at Vanderbilt University Medical Center.
Regeneron is hoping to start clinical trials for an antibody treatment for coronavirus in humans as soon as next month, and if everything goes right, perhaps have a treatment ready for widespread distribution by the end of the summer.

"We generated thousands of [antibodies] and then selected the most powerful and potent ones to grow up into an antibody cocktail," said company president Dr. George Yancopoulos.

Like any treatment under development, it might not pan out. But if it does, it could treat coronavirus and possibly also prevent infection for a period of time.

A vaccine would likely offer longer lasting immunity, but that would likely take longer to develop, with the earliest estimates set at January.

"I think antibodies will be finished first, and will be the bridge toward longer immunity, which will be conferred by vaccines," said Crowe, director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center.

'A guided nuclear warhead'

In mid-January, researchers at the Rockefeller University in New York City heard from the National Institutes of Health: Get to work because we hope to have coronavirus antibodies cloned by the spring.

About two months later, Rockefeller researcher Jill Horowitz found herself handing out fliers outside a supermarket in New Rochelle, New York, inviting people who'd recovered from coronavirus to learn more about the Rockefeller study.

The city -- and in particular one synagogue -- had been hit hard by a coronavirus outbreak.

"I'm Jewish, and I'm Orthodox, and I know people at Young Israel. I have friends in New Rochelle. Our kids went to school together, so I could go into the community and make my case," said Horowitz, executive director of strategic operations in the immunology laboratory at Rockefeller.

In all, more than 100 people donated blood for the study, many of them from the New Rochelle community. Some of their stories will be told in an upcoming documentary, "Rebel Blood The Race to Cure Covid-19."
The lead scientist in Rockefeller's monoclonal antibody effort compares it to battle, noting that convalescent plasma has been used for more than a century.

"If you're thinking about a war, and you're fighting a war with a drug that came out of the early part of the 20thcentury, the monoclonal antibody is like a guided nuclear warhead in comparison," said Dr. Michel Nussenzweig, a professor at Rockefeller.

Research by several US teams

Several other US teams also say they've cloned antibodies, including Vanderbilt, Regeneron, Lilly Pharmaceuticals and Distributed Bio.

Regeneron anticipates starting clinical trials next month and hopes to provide "hundreds of thousands of doses" to patients by the end of the summer, Yancopoulos said.

The company already makes monoclonal antibodies for several illnesses, including cancer, arthritis and asthma.

"We're using the same exact technology now to come up with a specific tailored approach against Covid-19," Yancopoulos said.

Other companies gave a longer timeline. For example, Crowe, the doctor at Vanderbilt, said he anticipates it will be around the first quarter of next year before his team might have a Covid monoclonal antibody treatment ready to distribute.

He said it's a good sign that several teams are working on monoclonal antibodies.

"I think the more groups we have working on it, all the better, and the more shots on goal we have for getting an effective prevention or treatment," he said.

 

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Just one way that treatments can affect mortality rates and outcomes, more study is required obviously, but it is being used right now by doctors. Blood clotting is a cause of mortality among covid -19 patients, particularly the younger ones and is one of the effects of the illness and an effective treatment for this can help to whittle down the mortality rate a bit more. This work indicates those on ventilators who were given blood thinners were over twice as likely to survive, it more than cut the mortality rate in half! 63% of those given anticoagulants survived versus 29% who did not get anticoagulants. These medications are already approved for this use too and there should be no problem using them for this purpose.
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Giving blood thinners to severely ill Covid-19 patients is gaining ground

Among sicker #coronavirus patients who were on ventilators in ICUs, 63% of those given anticoagulants survived versus 29% who did not get anticoagulants.

www.statnews.com

Giving blood thinners to severely ill Covid-19 patients is gaining ground


Treating Covid-19 patients with medicines to prevent blood clots might help reduce deaths in patients on ventilators, based on new observational data.

A team from Mount Sinai Health System in New York on Wednesday reported better results for hospitalized Covid-19 patients who received anticoagulant drugs compared to patients who didn’t. The data are preliminary and require confirmation in larger studies with a more robust design, the authors say about their study published in the Journal of the American College of Cardiology, but their findings add weight to medical guidelines.

While there are no firm data on the frequency of clotting problems in Covid-19 patients, there have been troubling anecdotal reports of patients whose lungs are peppered with tiny clots or who have suffered strokes. Last month, other Mount Sinai doctors detailed strokes in five Covid-19 patients in their 30s and 40s, an unusually young age for such a damaging cardiovascular event. Other reports of strokes have bubbled up elsewhere, including 88 patients in the original epicenter of the coronavirus in Wuhan, China, six in London, and three in Strasbourg, France.

Autopsies of 12 Covid-19 patients showed strong evidence for blood clotting problems, including clots in the lungs and in the legs, a group in Hamburg, Germany, reported Wednesday. In all 12 cases, the cause of death was found within the lungs or the pulmonary vascular system.

Together they add to accumulating evidence that Covid-19 leads to abnormal blood clotting and that anticoagulant medications might help.

The most recent Mount Sinai study analyzed data from more than 2,700 patients hospitalized for Covid-19. The percentage of patients who died while not on a ventilator to help them breathe was about the same, whether or not they received some form of anticoagulant. Time to death was a week longer for those who were given anticoagulants: a median of 21 days compared to 14 days for those who did not receive anticoagulants.

There was a mortality difference among sicker patients who were on ventilators in intensive care units: 63% of those given anticoagulants survived versus 29% who did not get anticoagulants. The patients were not randomly assigned to treatment or no treatment, however, meaning the study could not rule out other explanations for the apparent survival benefit.

Bleeding is a risk for patients who take anticoagulants, but the study found no significant difference between patients who did or did not receive anticoagulants.

“They interrogated their database of Covid-19 patients and came up with an interesting, thought-provoking finding that patients [on ventilators] who received full-dose, systemic anticoagulants had a lower mortality than those who did not, particularly patients in the intensive care unit,” said Jeffrey Weitz, president-elect of the International Society on Thrombosis and Haemostasis and a physician-scientist at McMaster University in Canada who was not involved in the study. “What it suggests to me is that anticoagulation alone might attenuate the disease, but it may not be the answer. We need more data and longer follow-up. Remember, this is just observational data. We don’t have a full picture on all of those patients.”

Based on the data in hand, Mount Sinai has changed its guidance on anticoagulants, said Valentin Fuster, a co-author of the study and physician-in-chief at Mount Sinai Hospital. Doctors had been giving patients anticoagulants before, using their clinical judgment. “We developed a new policy once we got these results,” Fuster said. “And that is to increase the dose of anticoagulants to the patients with Covid-19.”

Current guidelines from the American College of Cardiology for managing abnormal blood clotting in Covid-19 patients note that while most of its expert panel members recommend preventive doses of anticoagulants, a minority say they use the higher doses typically prescribed for patients with established blood-clotting problems. McMaster’s Weitz is a co-author of those guidelines. “What we’re really trying to find out is who should get it and how much,” he said about anticoagulant medication.

Anu Lala, another co-author and a cardiologist at Mount Sinai, said while the data reflect what she’s been seeing in the hospital, they demand more study.

“The very fact that there is a signal there is in line with what we seem to be observing clinically, having been on the wards for four weeks,” she said. “It opens the gate for us to do a deeper dive. There’s a lot more work to be done to prove or even really determine causality

One unknown: Did patients have an underlying cause for blood clots, such as the abnormal heart rhythm atrial fibrillation? Patients had their blood drawn when they were admitted to one of the five hospitals in the Mount Sinai system, and if they had inflammatory markers, they were put on oral, injected, or infused anticoagulants. Higher doses were given in the ICU.

In the earlier case reports on young Covid-19 patients who had strokes, there were no signs of blood-clotting disorders. J Mocco, a neurosurgeon at Mount Sinai, said that right when New York was seeing a surge in hospital admissions for Covid-19, he and colleagues in cardiology and pulmonology noticed a much higher than expected number of patients with stroke, amounting to a sevenfold increase over normal numbers. These patients were 15 years younger than typical stroke patients and they didn’t have risk factors for stroke such as irregular heartbeats or heart failure.

“I don’t want every person out there being petrified they’re going to have a stroke because of the coronavirus being out there,” he said. “But within this group of individuals, it does strongly suggest that the virus is contributory to their strokes.”

That argues for starting blood thinners sooner and looking at other measures, he said. “In some patients, we’re even trying clot-busting drugs to try to undo some of the clotting.”

Why Covid-19 patients have abnormal blood clotting isn’t known, but doctors suspect it’s related to inflammation and the ACE2 receptors the coronavirus latches onto, not only in the lungs and other organs but also on the lining of blood vessels. Inflammation and blood clotting normally go together, with a blood clot forming around the site of an infection. How this goes wrong in Covid-19 and whether it’s just one factor is still not understood.

At Mount Sinai, the next step is another observational study of 5,000 Covid-19 patients taking blood thinners to home in on why they were started on anticoagulants, followed by a randomized clinical trial based on what is learned.

“The more we learn, I think, the more we’re humbled, quite frankly,” Lala said. “We’ve got to keep going.”

 

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I don't know about this source, I never heard of them, but they seem legitimate, STAT is reliable though.
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Thetimesofus.com

Doctors lambaste federal process for distributing Covid-19 drug remdesivir

Hospitals and physicians across the nation are sharply criticizing the federal authorities for the uneven and opaque manner it’s distributing its provide of the Covid-19 drug remdesivir.

The experimental drug obtained an emergency use authorization from the Meals and Drug Administration final week, after preliminary data from a scientific trial confirmed that it diminished how lengthy it took hospitalized Covid-19 sufferers to recuperate. Now, because the drug’s producer, Gilead Sciences, tries to ramp up manufacturing, the U.S. authorities is beginning to distribute the restricted variety of vials that are not wanted for ongoing analysis, in order that sufferers can begin to see the profit outdoors of scientific trials.

About two dozen hospitals are believed to have been chosen to obtain the drug thus far, however clinicians advised STAT it’s unclear why some medical facilities had been chosen to obtain coveted doses whereas others weren’t — and who’s making these selections within the first place.

Extra from STAT Information:

“In my opinion, and I think in the opinion of many of my colleagues, there is a complete lack of transparency about how this decision is being made and who is making it,” stated Daniel Kaul, an infectious illness doctor on the College of Michigan. His hospital’s pharmacy division knowledgeable him that their middle would not be getting any doses of remdesivir after being involved with the drug’s non-public distributor, AmerisourceBergen, earlier on Wednesday.

“Those of us on the front lines treating people with Covid-19 need to know what the criteria are and where this drug is going to be available and why those places were selected,” he went on.”All of us want to make sure limited resources are used in the most efficient fashion … The government entity making this decision should reveal itself and it should state its criteria.”

Even medical facilities chosen to obtain the drug had been at the hours of darkness. “I legitimately do not have any insight into how hospitals were selected,” stated Paul Biddinger, director of Massachusetts Basic Hospital’s Middle for Catastrophe Medication and one of many chief’s of the hospital’s pandemic response.

On Tuesday night, he stated, the hospital’s pharmacy obtained affirmation that it will obtain sufficient remdesivir for about 170 sufferers. He had heard that three different medical facilities within the state additionally obtained allocations. Most different Massachusetts hospitals — together with some that had been among the many hardest hit by Covid-19 — would obtain none. Biddinger stated that on Wednesday, his crew was in contact with the Massachusetts Division of Public Well being about giving the company the hospital’s allotment, if federal rules allowed that form of switch.

“What we want is to make sure that everyone has fair access to the medication,” stated Biddinger. “We recognize that there are people from around the state that meet the criteria, and we certainly don’t want to be the only hospital [in metro Boston] with access to the medication.”

Earlier situations of unapproved medication being approved for emergency use have been very totally different, stated Michael Ison, an infectious illness doctor at Northwestern Medication. Throughout the H1N1 flu outbreak in 2009, he defined, the Facilities for Illness Management and Prevention created a web site as quickly because the FDA authotized emergency use for peramivir, in order that hospitals may apply for the medication.

Not so for remdesivir. “Currently there is no way anywhere I’ve seen to figure out how this is being distributed or how they’re making decisions about this,” Ison stated.

He came upon by way of his hospital’s head of pharmacy that Northwestern wouldn’t obtain any doses below the emergency use authorization. “This led me to reach out to leaders around the country who are focused on the care of these patients, and found that a huge number of large academic medical centers … didn’t have access to this drug,” he stated. Ison heard that about 25 hospitals have been authorised however that the College of Washington, College of California, San Francisco, Emory, Duke, Tufts, and Boston Medical Middle had all been advised they would not get any of the federal government’s provide of the drug.

The truth that a number of the hardest hit hospitals weren’t amongst these chosen was regarding, he stated. “It raises significant questions about how this was done. It’s not clear to anyone. There is no place this information can be found,” he stated.

Within the meantime, he stated, UCSF has change into one thing of a clearinghouse for info on which hospitals are gaining access to the drug. One infectious illness physician there posted a of the hospitals that obtained phrase of an approval or rejection.

“They (UCSF) is doing what the government should be transparent about,” Ison stated.

“I’m scared and nervous,” stated Peter Chin-Hong, a UCSF infectious illness physician. “There are places that are having a lot more cases than California. But what I’m worried about is, are we ever going to get it [remdesivir]? What is the speed at which we’re going to get it? And which hospitals in the area are going to get it if we’re going to get it at all.”

Chin-Hong stated a colleague in UCSF’s pharmacy division started gathering info from different hospitals to create a map of which facilities had been authorised to obtain the drug and which had been denied. At the same time as the knowledge began to change into public Wednesday, it was unclear which a part of the federal authorities was making the selections about which amenities will get entry to the drug, and why.

“We know who the vendor is — AmerisourceBergen — but we don’t actually know who is making the decision. Is it Trump? Is it FEMA? Is it science-informed?”

The Federal Emergency Administration Company advised STAT that the Division of Well being and Human Companies is dealing with remdesivir distribution; a HHS spokesperson stated they might look into the matter. Gilead declined to remark.

He stated sufferers and docs within the system are actively in search of entry to the drug. “This morning I got a call from one of the hospitals in our system in a different county. They didn’t have the drug and they just wanted to know what the options were for their patients.”

A part of the problem is that the information on the drug’s efficacy remains to be preliminary. “We don’t think, for the short term, there will be enough remdesivir to treat everyone,” stated Biddinger, “and so we would like to prioritize those who are most likely to benefit from the drug.”

Whereas many clinicians suspect treating a affected person earlier of their sickness might present extra profit, the proof is not printed but. That leaves hospital programs within the unenviable place of selecting who will obtain treatment with out all of the related info.

“The feeling at the end of the day is that it’s probably going to have to be a lottery,” stated Chuck Morris, the incident commander of Brigham and Girls’s Hospital, the place sufferers are receiving remdesivir as a part of a scientific trial, and which is a part of the identical system as Mass. Basic. Whereas there had additionally been discussions of getting to invoke disaster requirements of care, which can assist hospitals ration restricted medical assets in an effort to save lots of the best variety of lives, however there have been issues that that would introduce inequities, as a result of those that’ve had much less entry to the medical system might have extra underlying well being situations.

The Infectious Illness Society of America, on Wednesday afternoon posted a letter addressed to Vice President Mike Pence urging the administration to create a good and open process for distributing the drug.

“The plan for distributing remdesivir should be transparent and should be based on state and regional COVID-19 case data and hospitalization rates,” the letter states. “Supplies of remdesivir should be distributed on a regional basis with equitable distribution within the region to states and within states to hospitals.”

The group, which represents the nation’s infectious illness specialists, emphasised that creating such a process is especially necessary to remove bias and assist counteract well being disparities that are inclined to fall alongside racial traces. “Data on the distribution of remdesivir under the EUA should be publicly available,” it wrote. It added that knowledge from the finished scientific trial, the Adaptive COVID-19 Therapy Trial, ought to be publicly launched in order that hospitals with a restricted provide have the absolute best knowledge to tell the way to distribute remdesivir amongst sufferer

 

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Scientists say a now-dominant strain of the coronavirus could be more contagious than original

A mutation in the novel coronavirus has led to a new strain viewed as more contagious than the virus that emerged from China, according to a new study.

www.latimes.com

Here is some professional opinion on the mutation story, it was a computational analysis study, pure theory.
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Study on coronavirus mutation doesn't prove new strain is more infectious: Dr. Scott Gottlieb

A new, early study by researchers at the Los Alamos National Laboratory shows the coronavirus may be mutating and the new, dominant strain appears to be even more contagious. Dr. Scott Gottlieb, member of the boards of Pfizer and biotech company Illumina and former FDA commissioner, joins "Squawk Box" to discuss.

Dr. Scott Gottlieb on Wednesday urged caution about a new study that suggests the coronavirus has mutated, with the new, dominant strain appearing to be even more contagious.

“It doesn’t prove that this new strain is in fact more infectious,” Gottlieb said on CNBC’s “Squawk Box.”

According to researchers at the Los Alamos National Laboratory, the new strain of the coronavirus started to spread in Europe in early February and then migrated to other parts of the world, including the U.S. By the end of March, this new strain became the dominant form of the virus in the U.S. and Canada.

“The analysis could be confounded by the fact that this just became the dominant strain in Europe because it got into Europe early and then got into the United States from Europe,” argued Gottlieb, the former head of the U.S. Food and Drug Administration. “It really doesn’t prove anything.”

Gottlieb said the study, which has not yet been peer reviewed, is only based on computational analysis and therefore more work needs to be done. “We don’t have any other data to support it, including cell culture data.”

“We saw a change like this with Ebola and we initially thought that it also made Ebola more contagious and we actually had cell culture data to support it at that time,” said Gottlieb, a CNBC contributor who sits on the boards of Pfizer and biotech company Illumina. “We found that when we put it into animal studies, in fact the change in the virus didn’t change its contours at all, didn’t make it more infectious.”

Pfizer is developing a vaccine. If the study were to be proven correct, it may complicate vaccine development.

The Los Alamos researchers said the mutation was of “urgent concern” because of the more than 100 vaccines in the process of being developed to prevent Covid-19. Some vaccine researchers have been using the virus’s genetic sequences isolated by health authorities early in the outbreak, which began late last year in China.

 

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The Problem With Stories About Dangerous Coronavirus Mutations

There’s no clear evidence that the pandemic virus has evolved into significantly different forms—and there probably won’t be for months.

www.theatlantic.com

The Problem With Stories About Dangerous Coronavirus Mutations
There’s no clear evidence that the pandemic virus has evolved into significantly different forms—and there probably won’t be for months.

As if the pandemic weren’t bad enough, on April 30, a team led by scientists at Los Alamos National Laboratory released a paper that purportedly described “the emergence of a more transmissible form” of the new coronavirus, SARS-CoV-2. This new form, the team wrote, “began spreading in Europe in early February.” Whenever it appeared in a new place, including the U.S., it rapidly rose to dominance. Its success, the team suggested, is likely due to a single mutation, which is now “of urgent concern.

The paper has not yet been formally published or reviewed by other scientists. But on May 5, the Los Angeles Times wrote about it, claiming that “a now-dominant strain of the coronavirus could be more contagious than [the] original.” That story quickly went … well … viral.

But “the conclusions are overblown,” says Lisa Gralinski of the University of North Carolina, who is one of the few scientists in the world who specializes in coronaviruses. “To say that you’ve revealed the emergence of a more transmissible form of SARS-CoV-2 without ever actually testing it isn’t the type of thing that makes me feel comfortable as a scientist.” She and other virologists I’ve spoken with who were not involved in the Los Alamos research agree that the paper’s claims are plausible, but not justified by the evidence it presents. More important, they’re not convinced different strains of the coronavirus exist at all.

“We have evidence for one strain,” says Brian Wasik at Cornell University.

“I would say there’s just one,” says Nathan Grubaugh at Yale School of Medicine.

“I think the majority of people studying [coronavirus genetics] wouldn’t recognize more than one strain right now,” says Charlotte Houldcroft at the University of Cambridge.

Everyone else might be reasonably puzzled, given that news stories have repeatedly claimed there are two, or three, or even eight strains. This is yet another case of confusion in a crisis that seems riddled with them. Here’s how to make sense of it.

Whenever a virus infects a host, it makes new copies of itself, and it starts by duplicating its genes. But this process is sloppy, and the duplicates end up with errors. These are called mutations—they’re the genetic equivalent of typos. In comic books and other science fiction, mutations are always dramatic and consequential. In the real world, they’re a normal and usually mundane part of virology. Viruses naturally and gradually accumulate mutations as they spread.

Read: The best hopes for a coronavirus drug

As an epidemic progresses, the virus family tree grows new branches and twigs—new lineages that are characterized by differing sets of mutations. But a new lineage doesn’t automatically count as a new strain. That term is usually reserved for a lineage that differs from its fellow viruses in significant ways. It might vary in how easily it spreads (transmissibility), its ability to cause disease (virulence), whether it is recognized by the immune system in the same way (antigenicity), or how vulnerable it is to medications (resistance). Some mutations affect these properties. Most do not, and are either silent or cosmetic. “Not every mutation creates a different strain,” says Grubaugh. (Think about dog breeds as equivalents of strains: A corgi is clearly different from a Great Dane, but a black-haired corgi is functionally the same as a brown-haired one, and wouldn’t count as a separate breed.)

There’s no clear, fixed threshold for when a lineage suddenly counts as a strain. But the term has the same connotation in virology as it does colloquially—it implies importance. Viruses change all the time; strains arise when they change in meaningful ways.

New strains of influenza arise every year. These viruses quickly acquire mutations that change the shape of the proteins on their surface, making them invisible to the same immune cells that would have recognized and attacked their ancestors. These are clearly meaningful changes—and they're partly why the flu vaccine must be updated every year.

Read: Why some people get sicker than others

But influenza is notable for mutating quickly. Coronaviruses—which, to be clear, belong to a completely separate family from influenza viruses—change at a tenth of the speed. The new one, SARS-CoV-2, is no exception. “There’s nothing out of the ordinary here,” says Grubaugh. Yes, the virus has picked up several mutations since it first jumped into humans in late 2019, but no more than scientists would have predicted. Yes, its family tree has branched into different lineages, but none seems materially different from the others. “This is still such a young epidemic that, given the slow mutation rate, it would be a surprise if we saw anything this soon,” Houldcroft says.
more...

 

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https://www.washingtonpost.com/science/2020/05/06/urgent-quest-coronavirus-treatment-involves-door-to-door-blood-collection-llama-named-winter/

The urgent quest for a coronavirus treatment involves door-to-door blood collection and a llama named Winter
Antibody treatments could be a ‘bridge’ to a vaccine

The global search for a treatment targeting the novel coronavirus has led to an unlikely potential savior: a cocoa-colored llama named Winter, whose blood could hold a weapon to blunt the virus.
She lives at a research farm in Belgium with about 130 other llamas and alpacas. And like all of them, she produces a special class of disease-fighting antibodies — tiny, even by antibody standards — that show early promise in laboratory tests in blocking the novel coronavirus from entering and infecting cells.
In a paper published Tuesday in the journal Cell, an international team of scientists reports that these petite antibodies, harvested from Winter’s blood, were used to engineer a new antibody that binds to the spiky proteins that stud the surface of the novel coronavirus, “neutralizing” its insidious effect. The study, though preliminary, points to a possible treatment for covid-19, the disease caused by the coronavirus, if the results hold up in animal and human studies.

Winter the llama is the cuddly face of a broader — and urgent — scientific quest to create coronavirus drugs inspired by the targeted responses mustered by the immune system. Winter’s antibodies are a niche kind that are called nanobodies and are prized by researchers because of their ability to get into nooks and crannies and because they are slow to degrade in the body.
Other scientists are exposing laboratory mice to the coronavirus spike protein and studying the blood of people who have recovered from covid-19 to identify traditional antibody drugs. While work continues in the lab, U.S. hospitals are already harnessing naturally occurring antibodies to treat patients by providing experimental transfusions of blood plasma from covid-19 survivors, hoping the plasma, rich with virus-fighting antibodies, can save lives.

With a widely available vaccine probably at least a year away, antibody therapies have become, in the eyes of some experts, one of the most promising weapons against covid-19, which has killed more than 250,000 people worldwide.

Wayne Marasco, an infectious disease specialist at Dana-Farber Cancer Institute who developed experimental antibody therapies against close cousins of the current coronavirus, said he thinks the approach could be a “game changer.” A single dose could potentially act to treat the disease or to prevent it for months. Former Food and Drug Administration commissioner Scott Gottlieb wrote in the Wall Street Journal last month that such drugs “may be the best chance for a meaningful near-term success.”
The antibodies inspired by Winter are still far from being tested in people. Belgian researchers are only now starting preclinical trials on hamsters.
But other efforts to create more-traditional antibody drugs are moving forward fast, with the hope they could provide a bridge until there is a vaccine.

Regeneron Pharmaceuticals exposed a special strain of mice, genetically tweaked to have a human immune system, to the characteristic spike protein on the surface of the coronavirus to identify thousands of antibodies that show promise. The company also studied the blood of people who recovered. The company will start several human trials in June, testing antibody cocktails both as a treatment and a prevention measure for people who are at high-risk of developing covid-19. The company hopes to make the treatment available by the end of summer or early fall, with the ability to manufacture hundreds of thousands of doses.
“It’s never been done before,” George Yancopoulos, chief scientific officer of Regeneron, told investors Tuesday. “On the other hand, I don’t think we ever had quite a pandemic like this before... And so the hope is yes, it might be possible by the end of the summer or the fall that our antibody treatment could be available. A lot of risks, a lot of concerns, but we are working as hard as we can with so many collaborators to try to turn that into a reality.”
Vir Biotechnology, which also plans to start human tests this summer, hired a nationwide network of phlebotomists to go door-to-door collecting blood from people who recovered from covid-19 to aid the search for an antibody-based treatment. The company that did the blood draws, Sanguine Biosciences, sent phlebotomists to people at home to reduce the risk of infection, saving recently recovered people a trip to a crowded clinic or laboratory.

A research team from Utrecht University in the Netherlands reported Monday in the journal Nature Communications that it had created a monoclonal antibody called 47D11 that is capable of neutralizing the coronavirus in laboratory tests.
Such drugs are manufactured not by chemists but by living cells growing in bioreactor vats and tend to be expensive; they must be given by injection. Even now, with little idea of whether their drugs will be shown safe and effective, researchers are thinking about how to increase production.
“It takes time to scale, and we’re already scaling,” said George Scangos, chief executive of Vir. “The problem with this whole approach is you have to scale before you know if your drug works. Because if you don’t [scale], and your drug works — now it’s a year before you can provide any reasonable number of doses, and that’s not a situation that anyone wants to be in.”
The fastest way to a coronavirus treatment would be to repurpose an existing drug with a long safety record. To that end, scientists are pulling many time-tested drugs off the shelf to see whether they show promise in laboratory experiments and are moving some into the clinic. But antibody treatments could provide a powerful and targeted way to quickly develop a new drug that not only treats the disease but also could prevent people from becoming ill.

Much of this research already has a head start based on experience with severe acute respiratory syndrome (SARS). Marasco developed a library of 27 billion human antibodies from blood samples taken from hospital staffers in the late 1990s, which he then used to develop experimental therapies for SARS and Middle East respiratory syndrome (MERS). Those therapies were licensed to companies, but government and commercial interest evaporated when those viral outbreaks petered out. Marasco is working now on antibody therapies for the novel coronavirus, confident that this time things will be different.

Winter’s part in the battle against coronavirus disease began in 2016, when researchers immunized her with spike proteins from MERS and SARS. Then they drew her blood and isolated antibodies, one of which showed potential for neutralizing MERS, and another of which neutralized SARS, said Daniel Wrapp, a co-author of the study and graduate student at the University of Texas at Austin.
The Texas team, working with colleagues at the U.S. National Institutes of Health and Ghent University in Belgium, was trying to develop a universal vaccine for human coronaviruses, four of which are common and cause cold-like symptoms. While the researchers were hoping to find a single antibody that could target all the coronaviruses, the “consolation prize” was finding two that showed promise against MERS and SARS, Wrapp said.
They were writing up what they’d learned from Winter when the novel coronavirus emerged. They quickly got to work. Soon, they’d found that a new antibody — which they created by linking two copies of the llama antibody that had hindered the original SARS — was able to bind to and neutralize the novel coronavirus, known as SARS-CoV-2, Wrapp said.
“It’s interesting to have a renewed sense of urgency toward your work, because it could have such dramatic implications for vaccine development and therapeutic” treatments, Wrapp said.

If the small antibodies work in humans, their stability means they possibly could be delivered as treatment via an inhaler, Wrapp said. Larger monoclonal antibodies must be administered by injection.

Winter was randomly selected from her herd to participate in this research, noted Wrapp, who has never met the 4-year-old llama. Now, he said, “she’s kind of the superstar of this.”

 

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I wonder if Donald involved himself in this too, he fucks up everything he touches. Maybe he has a VIP list of friends he's hoarding it for and the red states will need lots soon too... Donald craves to hold the power of life and death in his tiny hands, so I figure he's getting some for himself and friends at least, we 've seen how he did it with ventilators and PPE. He's a wartime president alright, he's just at war with the blue states, the truth, the media, the congress, the constitution, the rule of law and the courts.
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Hospitals criticizing government over distribution of remdesivir

Eric Boodman, Stat News, reports that hospitals are already complaining about the federal government's distribution of the drug remdesivir. With Dr. Scott Gottlieb.

 

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News stories like this will drive demand up and more will come complete with recovered patient interviews.
-------------------------------------------------------------------------------------------------------------------------------
Local Hospitals Seeing Positive Results With Remdesivir

Some COVID-19 patients on the verge of death recovered after taking Remdesivir.

 

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Convalescent plasma therapy reduced the SARS mortality rate of 15%* by 20% and Covid -19 has a much lower mortality rate of around .5%** so it might be even more effective with this disease. It's being widely used and studied at the same time and the rate of transfusions will increase greatly if a study data of efficacy is released. This treatment is cheap and can be quickly deployed using existing blood bank infrastructures that are available in most countries. America could easily transfuse tens of thousands of severely ill people a day if required and it was proven to be effective. Even if only 20% effective like in SARS in reducing mortality rates, that's still 200 thousand people saved out of a million possible deaths in the USA over the next year. I believe it can do much better than 20% with this disease, more so when the treatment and protocols are developed.

*SARS Global deaths: 774; 15 percent mortality rate; no U.S. deaths

** Covid-19 Global deaths to date: Over 4,700; the global death rate is estimated at 3.4 percentTrusted Source, but certain areas are seeing a death rate of just 0.4 percent
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Patients in UK hospitals given plasma from people who've already recovered | 5 News

Trials to find a possible treatment for Covid-19 took a big step forward today, as patients in UK hospitals were given plasma from people who've already recovered.

It's hoped that the transfusions will both improve their chances of survival and speed up their recovery.

 

[captainmorgan]

I keep bringing this up but never hear about it in the media, there are a lot of people surviving this virus that are permanently damaged and disabled.

Science | AAAS

www.sciencemag.org

 

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I keep bringing this up but never hear about it in the media, there are a lot of people surviving this virus that are permanently damaged and disabled.

Science | AAAS

www.sciencemag.org

A lot of this damage appears to be caused by two related things, an immune overreaction and blood clotting issues, particularly the lung damage seems to be from by micro clotting caused by the virus. They can now test for those vulnerable to this condition and blood thinners and drugs can help a lot with this part of the illness. Blood thinners alone appear to have more than doubled the survival of those on ventilators and other drugs deal with the immune response. Ventilators are the end of the line and if you double the survival rate for those on them with blood thinners alone, you take a bite out of the overall mortality rate.

 

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Triple drug therapy helps coronavirus patients recover more quickly, study finds | CNN

Coronavirus patients given a three-drug cocktail got better more quickly, Hong Kong researchers reported.

www.cnn.com

Triple drug therapy helps coronavirus patients recover more quickly, study finds

(CNN)A combination of three antiviral drugs plus an immune system booster seemed to help patients recover more quickly from coronavirus infections, doctors in Hong Kong reported Friday.
They said the approach needs more testing but it could offer another treatment possibility for Covid-19 patients. Currently the only authorized treatment is the experimental antiviral drug remdesivir, which also shortens the duration of illness but is limited in supply.
Dr. Kwok-Yung Yuen at Hong Kong University and colleagues tested the HIV drug combination of ritonavir and lopanivir along with the general antiviral drug ribavirin and a multiple sclerosis drug called beta interferon.

US government will decide where remdesivir goes amid coronavirus pandemic, drugmaker says

Patients in the study all had mild to moderate symptoms and were treated within seven days of testing positive. Some doctors think treating patients earlier in the course of the infection might be better.


Yuen's team gave some patients only the HIV drug combination, often sold under the brand name Kaletra. Other were randomly assigned to get the lopinavir-ritonavir combination plus the antiviral drug ribavirin and injections of beta interferon.
The patients who got the cocktail tested negative for coronavirus after seven days on average. Those who just got the HIV drugs were positive on average for 12 days, the team reported in the Lancet medical journal.

Few side effects, study says
The patients given the cocktail also felt better quicker -- within four days.
"Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19," the researchers wrote.
There were few side effects, they added.

FDA issues emergency-use authorization for remdesivir to treat hospitalized patients with severe Covid-19

Dr. Peter Chin-Hong, who is treating coronavirus patients at the University of California San Francisco, said the study offers new hope in the pandemic.
"This study is really refreshing because it tells us remdesivir isn't the only game in town and maybe there are other options around," he told CNN.
"These drugs have a track record of safety," he said, adding they are also easily available.
Doctors and pharmacists have complained that they don't know which hospitals and clinics will get remdesivir, which was given US Food and Drug Administration emergency use authorization after it was shown to reduce the duration of illness in Covid-19 patients.
Chin-Hong said the Lancet study showed the possibility of other treatments.
"Maybe we can get this when we can't get the alleged magic bullet," he said.

Many groups are testing various combinations of drugs against coronavirus. Nothing is likely to be a cure, doctors agree.
"In Covid-19 we don't have the luxury of time," Chin-Hong said. "This is one of the treatment options where we are teaching old drugs new tricks. We don't have the time to take a drug rationally from beginning to end because we have a crisis right now. We have to make do with what we have."

 

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SSRN Electronic Library

Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19)

9 Pages Posted: 9 Apr 2020 Last revised: 7 May 2020


Mark Alipio
Davao Doctors College; University of Southeastern Philippines
Date Written: April 9, 2020

Abstract
The rapid spread of COVID-19 in many areas of the world calls for preventive health measures. Although basic guidelines on infection control are suggested, treatment has remained the best choice to avert mortality. However, for the time being, there are no known vaccines for the disease. In this paper, a multinomial logistic regression was used to predict clinical outcomes of patients infected with COVID-19 based on 25-hydroxyvitamin D [25(OH)D] levels, the barometer for Vitamin D status. A retrospective multicentre study of 212 cases with laboratory-confirmed infection of SARS-CoV-2 was conducted. Data pertaining to clinical features and serum 25(OH)D levels were extracted from the medical records. For statistical analysis, Mann-Whitney U and χ² tests were used to compare differences in the clinical outcomes. Multinomial logistic regression was used to explore the association between serum 25(OH)D level and clinical outcomes of the cases. Frequency and percentage were used for categorical variables. Mean was used for continuous variables. A p-value below 0.01 was considered statistically significant. Of the 212 cases of COVID-19, majority had ordinary clinical outcome. Mean serum 25(OH)D level was 23.8 ng/ml. Serum 25(OH)D level was lowest in critical cases, but highest in mild cases. Serum 25(OH)D levels were statistically significant among clinical outcomes. Majority had insufficient Vitamin D status, most of them were not severe. Vitamin D status is significantly associated with clinical outcomes. A multinomial logistic regression analysis reported that for each standard deviation increase in serum 25(OH)D, the odds of having a mild clinical outcome rather than a severe outcome were approximately 7.94 times (OR=0.126, p<0.001) while interestingly, the odds of having a mild clinical outcome rather than a critical outcome were approximately 19.61 times (OR=0.051, p<0.001). The results suggest that an increase in serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while a decrease in serum 25(OH)D level in the body could worsen clinical outcomes of COVID-2019 patients. In conclusion, this study provides substantial information to clinicians and health policy-makers. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with COVID-19. Further research should conduct randomized controlled trials and large population studies to evaluate this recommendation.

 

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Vitamin D insufficiency is prevalent in severe COVID-19

Background COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes...

www.medrxiv.org

Vitamin D Insufficiency is Prevalent in Severe COVID-19

Abstract
Background: COVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. Methods: In an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. Results: Twenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. Conclusions: VDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.

 

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https://www.medrxiv.org/content/medrxiv/early/2020/04/10/2020.04.08.20058578.full.pdf?mod=article_inline

The Role of Vitamin D in Suppressing
Cytokine Storm in COVID-19 Patients and
Associated Mortality
Ali Daneshkhah1
, Adam Eshein1
, Hariharan Subramanian1
, Hemant K.
Roy 2
, and Vadim Backman1
1 Department of Biomedical Engineering, Northwestern University
2 Boston Medical Center
Abstract
Background
Statistical analysis of data obtained from hospitals and clinics across the world has been
analyzed to illuminate new insights into characteristics of COVID-19 and to discern
whether a link exists between severe cases of COVID-19 that feature cytokine storm and
vitamin D (Vit D) deficiency.
Method
Daily admission, recovery and deceased rate data for patients with COVID-19 from
countries with over 5,000 confirmed cases through March 21, 2020, were selected. A
potential association between severe Vit D deficiency and age-specific case fatality (CFR)
was investigated. Reported medical characteristics of 793 COVID-19 patients were used
to evaluate the intensity of cytokine storm in severe COVID-19 using C-reactive protein
(CRP) levels. Medical data reported from a national study of 3,848 participants in 2007-
2008 was used to investigate the association between Vit D status and CRP. Odds ratio
and risk factors from these conditions were used to predict the potential impact of Vit D
on the reduction of cytokine storm and severe COVID-19.

Findings
Age-specific CFR in Italy, Spain, and France (70 yo ≤ age < 80 yo) was substantially
higher (>1.9 times) than other countries (Germany, South Korea, China); for the elderly
(age ≥70 yo), Italy and Spain present the highest CFR (>1.7 times that of other countries).
The age-specific ratio of confirmed cases in Italy, Spain, and France has also been
substantially higher than in other countries. A more severe deficiency of Vit D (mean 25-
hydroxyvitamin D (25OHD) concentration <0.25 ng/L) is reported in Italy and Spain
compared to other countries. Our analysis of the reported clinical data (25OHD, CRP)
from multiple studies suggests that elimination of severe Vit D deficiency reduces the risk
of high CRP levels (odds ratio of 2) which may be used as a surrogate marker of cytokine
storm which was estimated to a potential reduction in severe COVID-19 cases of up to
15%.

 

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Study shows Covid-19 patients who took heartburn drug were less likely to die, but researchers caution more research is needed | CNN

Patients who took a common heartburn medicine while hospitalized for Covid-19 were more than twice as likely to survive the infection, according to a paper posted Friday on a pre-publication website. But it's unclear whether the patients fared better because of the famotidine or if it was a...

www.cnn.com

Study shows Covid-19 patients who took heartburn drug were less likely to die, but researchers caution more research is needed

(CNN)Patients who took a common heartburn medicine while hospitalized for Covid-19 were more than twice as likely to survive the infection, according to a paper posted Friday on a pre-publication website. But it's unclear whether the patients fared better because of the famotidine or if it was a coincidence.

"Based on what we've learned in this study, it's encouraging," said Dr. Joseph Conigliaro, a coauthor of the paper and a physician at Northwell Health. "This association is actually really compelling."
The drug, famotidine, has been on the market for nearly 40 years and is an active ingredient in the popular over-the-counter heartburn treatment Pepcid.
Among the 1,536 patients in the study who were not taking famotidine, 332, or 22%, either died or were intubated and put on a ventilator. Among the 84 patients who were taking famotidine, 8, or 10%, died or were put on a ventilator.
"Compared to the rest of the patients, those who received famotidine had a greater than 2-fold decreased risk of either dying or being intubated," according to a statement by authors of the study at Columbia University Irving Medical Center.

The patients who were taking famotidine started the drug within 24 hours of being admitted to the hospital. Some took it orally and some intravenously, at varying dosages. About 15% of them were already taking it at home.
The study doesn't prove the drug caused the lower death rate -- it's possible that it's just a coincidence.
"It is not clear why those patients who received famotidine had improved outcomes," the authors wrote in their statement. "This is merely an association, and these findings should not be interpreted to mean that famotidine improves outcomes in patients hospitalized with COVID-19."
Doctor cautions against starting famotidine
The study was published on medrxiv.org, a preprint server founded by Yale University, the medical journal BMJ and Cold Spring Harbor Laboratory in New York. Articles on this server have not been reviewed by authors' scientific peers.
Based on these results, Conigliaro said he knows that doctors might start prescribing famotidine to their coronavirus patients now, before the results of the clinical trial are known, but he doesn't recommend it.
"I think doctors should wait for more data from the prospective trial," he said.

He added that there's no evidence famotidine prevents infection, and he's concerned that people who don't have Covid-19 will start taking it.
"I would really caution against this. Taking famotidine might give them a false sense of security," he said.
Only a clinical trial, where patients are randomly assigned to get either famotidine or a placebo and then studied, can determine if the drug really works against Covid-19.
Northwell and Columbia are now doing a clinical trial where some patients are receiving intravenous famotidine at a dosage nine times higher than what is given for heartburn. Others are receiving a placebo, or a drug that does nothing. Conigliaro, who's heading up that trial, said preliminary results would likely be announced in a few months.
He said 233 patients have been enrolled in the study, and Northwell had planned to announce preliminary results when they enrolled 390 patients. However, since the number of patients with coronavirus in New York has declined, they might decide to announce the preliminary results with fewer patients.
'We don't know if it has any benefit'
It has a bit of a mystery why a heartburn medicine might help someone with a viral infection.
"A month ago when we were approached with the idea to start up the trial, I really did a double take," Conigliaro said.
The Northwell doctors decided to study famotidine for two reasons.
One, a computer modeling study showed that the famotidine's mechanism of action -- the way it fights heartburn and reflux -- might also help against Covid-19.
Two, Dr. Michael Callahan, an infectious disease specialist at Massachusetts General Hospital who worked with coronavirus patients in China, observed that lower income patients with heartburn were surviving longer than their wealthier counterparts who also had heartburn.
When Callahan and the Chinese doctors looked closer, they found that many of the people with lower incomes were taking famotidine, whereas the wealthier patients tended to take a different, more expensive drug.
more...