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https://s3.us-west-1.wasabisys.com/virusreports/2020/05/cropped-virus-favicon-32x32.png Treatment Archives - Virus Reports http://virusreports.net/tag/treatment/ 32 32 Hair loss treatment http://virusreports.net/hair-loss-treatment/ http://virusreports.net/hair-loss-treatment/#respond Sat, 19 Sep 2020 09:21:08 +0000 https://virusreports.net/hair-loss-treatment/ Hair loss can be a natural part of the ageing process, and most of the time, it's nothing to worry about. We can even lose up to 100 hairs on our bodies every day, without even noticing. But you could prolong the life of your locks by regularly eating avocados, it's been revealed. Losing your…

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Hair loss can be a natural part of the ageing process, and most of the time, it’s nothing to worry about. We can even lose up to 100 hairs on our bodies every day, without even noticing. But you could prolong the life of your locks by regularly eating avocados, it’s been revealed.

Losing your hair could be caused by a number of different conditions, said the NHS.

Stress, weight loss, or even an iron deficiency can lead to some form of hair loss.

But, there are some home treatments you can use that might help to prevent some types of hair loss, including alopecia.

One of the easiest ways to stimulate hair growth at home is to add more avocado to your diet, it’s been claimed.

READ MORE: Hair loss treatment – the supplements proven to prevent hair thinning

Hair loss treatment: Prevent alopecia symptoms and

Hair loss treatment: Prevent alopecia symptoms and stimulate hair growth with avocado in your diet (Image: GETTY Images)

Avocado could protect against hair loss as its rich in vitamin E, according to dietitian Ryan Raman.

Vitamin E protects the skin against damage and oxidative stress, he said.

If the skin on top of the head becomes damaged, it increases the risk of poorer hair quality and reduced hair follicles.

A single avocado provides around 20 percent of your daily vitamin E requirements.

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“Although you can’t change factors like age and genetics, diet is one thing you have control over,” Raman wrote for medical website Healthline.

“Eating a balanced diet with the right nutrients can help promote hair growth, especially if you’re experiencing hair loss due to poor nutrition.

“Avocados are delicious, nutritious and a great source of healthy fats. They are also an excellent source of vitamin E, which may promote hair growth.

“Vitamin E also protects areas of the skin, like the scalp, from oxidative stress and damage. Damaged skin on the scalp can result in poor hair quality and fewer hair follicles.”

Hair loss treatment: Speak to a doctor if your

Hair loss treatment: Speak to a doctor if your hair suddenly starts falling out (Image: GETTY Images)

Meanwhile, you could also protect against hair loss by eating more sweet potato, he added.

Sweet potatoes are a great source of beta-carotene, which is subsequently converted into vitamin A.

Vitamin A promotes the production of sebum, which is crucial to keeping your hair healthy.

It has also been claimed to speed up the rate of hair growth, while encouraging thicker hair.

Losing your hair isn’t necessarily something to be worried about.

But, on rare occasions, it could be a tell-tale sign of another medical condition.

You should speak to a doctor if you suddenly start losing your hair, or if you develop bald patches.

There are other treatments for hair loss – including transplants – but they aren’t available on the NHS, and you’ll need to pay for them.

Read More

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New plasma treatment under development in Georgia http://virusreports.net/new-plasma-treatment-under-development-in-georgia/ http://virusreports.net/new-plasma-treatment-under-development-in-georgia/#respond Wed, 22 Jul 2020 05:20:55 +0000 https://virusreports.net/new-plasma-treatment-under-development-in-georgia/ The idea is the antibodies in Weinrich’s plasma can help a sick patient fend off the infection. The 58-year-old computer programmer has donated his plasma, the antibody-rich liquid portion of his blood, four times over the past three months.“I’m sort of squeamish about needles, but I thought if I could turn my negative into a…

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The idea is the antibodies in Weinrich’s plasma can help a sick patient fend off the infection. The 58-year-old computer programmer has donated his plasma, the antibody-rich liquid portion of his blood, four times over the past three months.

“I’m sort of squeamish about needles, but I thought if I could turn my negative into a positive, if I could help someone who is presumably a lot worse than me because they are in the hospital, I had to do it,” said Weinrich, who lives in Watkinsville.

Kevin Weinrich has donated plasma multiple times. He said he was thankful his employer, Vision Technologies, allowed him to take time off from work to donate plasma.

In the absence of a vaccine or proven treatments, doctors are increasingly looking to this century-old approach to a new and raging public health emergency. Hospitals have been transfusing what’s called convalescent plasma directly to sick patients. But this experimental treatment is limited not only by supply shortages but also because each person’s plasma has varying levels of antibodies and the transfusions require matching blood types.

Now, researchers are working on another approach that could overcome those limits. This therapy may be available this year, even well before a vaccine.

And a major hub for the research is in Georgia.

Takeda Pharmaceuticals, one of the largest biopharmaceutical firms in the world, has a $2 billion state-of-the-art facility stretching more than 1 million square feet just east of Covington. That facility, which employs about 1,000 people, now has a dedicated space and team of researchers focusing on the potential COVID-19 treatment called hyperimmune globulin, a type of plasma-derived therapy that could provide a reliable, consistent, and more potent level of antibodies. The treatment would also have a longer shelf life of 24 to 36 months compared to 12 months for convalescent plasma transfusions.

ExploreAJC COMPLETE COVERAGE/CORONAVIRUS

Bottles of frozen convalescent plasma are prepped prior to the start of the fractionation process. Fractionation is the process of extracting proteins, including antibodies, from plasma.
PROVIDED BY TAKEDA

Several other pharmaceutical companies, including competitors, such as CSL Behring, teamed up with Takeda to form an alliance to accelerate the development of the therapy. The alliance hopes to start clinical trials at several hospitals in the U.S. during the coming weeks. The facility in Georgia will manufacture the potential therapy for the U.S. trials.

Both methods of plasma therapy rely on willing and able donors. But plasma supplies are desperately short, as hospitalizations surge again. A national coalition which includes the Mayo Clinic has launched a push for plasma donations in a campaign called, “The Fight is In Us.”

To aid collection for its proposed therapy as well as other plasma-derived therapies, Takeda, a Japanese company headquartered in Tokyo, has invested in eight BioLife Plasma Services collection centers in Georgia.

ExploreIn the race to treat COVID-19, Georgia companies stake a claim

A Takeda scientist sets up a chromatography system (a step in the process of separating antibodies from plasma) to use for the manufacturing process of a hyperimmune globulin for COVID-19.

Efficacy still being evaluated

Convalescent therapy is generally considered safe, according to Mayo Clinic, which is overseeing a national expanded access program for convalescent therapy and leading a large study on the effectiveness of the therapy, gathering data from hospitals across the country, including hospitals in Georgia.

Still, doctors stress that there are questions about how well plasma therapy will work for people sick with COVID-19.

Chinese researchers treating COVID-19 patients have reported limited success using convalescent therapy, albeit not in randomized, controlled studies — the gold standard in clinical research.

Dr. Kent Holland, medical director of Northside Hospital’s blood and marrow transplant program, said the death rate of critically ill patients receiving convalescent plasma at Northside Hospital is much lower than the death rates reported in New York City during earlier months of the pandemic. He said this suggests plasma therapy, along with other treatment interventions that include the antiviral drug remdesivir, is making a difference and helping patients recover, though he said more research and studies are needed to determine plasma therapy’s therapeutic efficacy. About 400 patients at Northside Hospital have received convalescent plasma.

ExploreExperts hopeful but cautious about new coronavirus treatment report

Dr. Sean Stowell, medical director for the Center for Apheresis (blood donation) at Emory University Hospital, said they’ve seen anecdotally encouraging results from convalescent therapy. A newborn baby testing positive for COVID-19 was recently given convalescent therapy and, a few days later, the virus “was not detectable.”

Stowell said plasma therapy is actually “old school” and with it generally considered safe, he believes “might as well give it a try.”

Doctors also expressed concern the therapy is not as effective as it might be because many patients receive it too late in the course of the disease.

It sometimes also takes days for the plasma to arrive, especially now. Most hospitals get it from blood banking centers, but even with those that have centers on-site, it can take several days to receive the plasma, which may be too late. The development of plasma-derived therapy is also dependent on donations from people, and whether or not it could keep up with demand remains to be seen.

Stowell said another issue is the varying degrees of antibodies in survivors’ blood. After Emory started independently testing antibody levels in donated blood from blood banks, he said about 20% were found to have “very, very low antibodies.”

It’s unclear what the ideal threshold for antibodies would be. Another lingering question is how long a person with antibodies would be immune to the coronavirus and whether a person can get infected more than once.

“We try not to practice by anecdotes, but by data and science,” said Dr. Amy Hajari Case, medical director of pulmonary/critical care research at Piedmont Hospital. “Now that said, our options are seriously limited. There are limited tools in our toolbox, and this is something that possibly can help, and we are glad we can provide this.”

Aerial photo of Takeda’s massive facility in Georgia.

Giving people hope

Plasma therapy works differently than a vaccine. When a person gets a vaccine, their own immune system actively produces antibodies to attack a pathogen. That’s called active immunity. Convalescent therapy offers what’s called “passive” immunity. It “borrows” the antibodies from someone who has successfully fought off the disease.

Before the development of antibiotics and vaccines, plasma therapy was used for a range of infectious diseases, including the Spanish flu in 1918, as well as meningitis and measles. During the 1918 flu pandemic, the rate of mortality decreased by as much as 50 percent among patients who received convalescent plasma, according to a meta-analysis of medical records available at that time and published in the Annals of Internal Medicine in 2006.

Plasma-derived therapies are used today for a wide variety of diseases and conditions, including autoimmune conditions and blood disorders, including hemophilia, an inherited bleeding disorder.

And when other treatments are unavailable, convalescent therapy has continued to be used, including for treating Severe Acute Respiratory Syndrome (SARS) and Ebola.

Studies of convalescent plasma therapies for SARS in 2003 and the 2009 H1N1 influenza showed measurable reductions of mortality, but efforts to treat Ebola virus infections during the 2014-16 outbreak in West Africa were inconclusive.

Carlos Soto, vice president of manufacturing for Takeda and site head of the Covington facility, said he remembers starting the conversation in February about working on a potential COVID-19 therapy.

“There is nothing novel about this, this is what we do every day, the only difference is the plasma comes from those who recovered from COVID-19,” Soto said.

If early data is strong, the treatment could be fast-tracked through clinical studies and regulatory review.

Meanwhile, Sidney Smith, a 29-year-old Georgia State police officer, and COVID-19 survivor, recently donated blood and plans to donate again. He said the process took about an hour. He said he realizes the benefits are still being evaluated, but even the possibility he could be helping is good enough.

“Even if it’s not an absolute lifesaver, if it is giving people hope, that’s good enough,” he said.

Donating Plasma

If you have had COVID-19 and want to donate plasma, you must be fully recovered to be eligible. You must be symptom-free for at least 14 days.

You must also meet standard requirements for all blood donors such as feeling well and minimum age and weight requirements. High school students who are at least 16 years of age require one-time parental consent. Other donors must be at least 17 years old. Your local blood donation site will ensure you meet the necessary criteria before donating.

Plasma donations compensation can vary based on weight and other factors, but donors can receive an average of about $75 per donation.

Survivor Corps, (www.survivorcorps.com/) an advocacy group, founded to mobilize COVID-19 survivors and encourages survivors to donate plasma, provides information about donating plasma and information about plasma donation sites.

About Plasma

Plasma is the often-forgotten part of blood. White blood cells, red blood cells, and platelets are all important for body function. But plasma also plays a critical role. This yellow fluid carries the blood components throughout the body. Along with water, salt, and enzymes, plasma also contains important components which include antibodies. It’s often called “liquid gold.”

Read More

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‘Breakthrough’ treatment slashes coronavirus death risk: UK study http://virusreports.net/breakthrough-treatment-slashes-coronavirus-death-risk-uk-study/ http://virusreports.net/breakthrough-treatment-slashes-coronavirus-death-risk-uk-study/#respond Mon, 20 Jul 2020 13:21:05 +0000 https://virusreports.net/breakthrough-treatment-slashes-coronavirus-death-risk-uk-study/ There are currently a number of treatments available for patients hospitalised with COVID-19 [File: Tolga Akmen/AFP] An aerosol-based drug treatment could drastically reduce the number of new coronavirus patients dying from the disease or requiring intensive care, according to preliminary results released by a British biotech firm. In a randomised trial of 100 patients admitted…

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There are currently a number of treatments available for patients hospitalised with COVID-19 [File: Tolga Akmen/AFP]

There are currently a number of treatments available for patients hospitalised with COVID-19 [File: Tolga Akmen/AFP]

An aerosol-based drug treatment could drastically reduce the number of new coronavirus patients dying from the disease or requiring intensive care, according to preliminary results released by a British biotech firm.

In a randomised trial of 100 patients admitted to hospital with COVID-19, those who received an inhaled formula of the protein interferon beta were at 79 percent lower risk of developing the severe disease compared with those who received a placebo.

They were also more than twice as likely to make a full recovery compared with the control group.

The firm behind the treatment, known as SNG001, said the preliminary results suggested “a major breakthrough” in the pandemic.

“We are all delighted with the trial results announced today, which showed that SNG001 greatly reduced the number of hospitalised COVID-19 patients who progressed from requiring oxygen to requiring ventilation,” said Richard Marsden, CEO of Synairgen.

The results published on Monday have not yet been peer-reviewed and the sample size is relatively small. But if confirmed the treatment could revolutionise the way COVID-19 is dealt with in hospitals.

Interferon beta

Interferon beta is a naturally occurring protein, commonly used to treat multiple sclerosis.

It forms part of the body’s natural fight against infection, and the novel coronavirus suppresses its production in an attempt to evade an immune response.

Delivering the protein directly into the lungs of patients is designed to trigger a robust immune response to the virus, even in patients whose immune system is already weakened by infection.

“The results confirm our belief that interferon beta … has huge potential as an inhaled drug to be able to restore the lung’s immune response,” said Tom Wilkinson, professor of respiratory medicine at the University of Southampton.

He said the trial showed SNG001 was effective in “enhancing protection, accelerating recovery and countering the impact of SARS-CoV-2 virus”.

There are currently a number of treatments available for patients hospitalised with COVID-19.

Last month, a UK-based team of researchers led by the University of Oxford announced they had successfully reduced the risk of death among seriously ill patients by administering the commonly available steroid dexamethasone.

Several countries have also issued the emergency authorisation for treatment with anti-viral remdesivir.

SOURCE:
News agencies

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Coronavirus Drug and Treatment Tracker http://virusreports.net/coronavirus-drug-and-treatment-tracker/ http://virusreports.net/coronavirus-drug-and-treatment-tracker/#respond Thu, 16 Jul 2020 15:21:03 +0000 https://virusreports.net/coronavirus-drug-and-treatment-tracker/ We rated 20 coronavirus treatments for effectiveness and safety: 5 3 7 2 3 We rated 20 coronavirus treatments for effectiveness and safety: 5 3 7 2 3 We rated 20 coronavirus treatments for effectiveness and safety: 5 3 7 2 3 The Covid-19 pandemic is one of the greatest challenges modern medicine has ever…

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We rated 20 coronavirus treatments for effectiveness and safety:

5

3

7

2

3

We rated 20 coronavirus treatments

for effectiveness and safety:

5

3

7

2

3

We rated 20 coronavirus treatments

for effectiveness and safety:

5

3

7

2

3

The Covid-19 pandemic is one of the greatest challenges modern medicine has ever faced. Doctors and scientists are scrambling to find treatments and drugs that can save the lives of infected people and perhaps even prevent infection.

Below is an updated list of 20 of the most-talked-about treatments for the coronavirus, including some of the most promising, interesting and potentially harmful. We also included a warning about a few that are just bunk.

The F.D.A. has not fully licensed any treatment specifically for the coronavirus, but it has granted emergency use authorization to a few.

For the current status of vaccine development, see our Coronavirus Vaccine Tracker.

What the Ratings Mean

We rate each treatment based on the scientific evidence for its effectiveness and safety. We’ll update and expand the list as more evidence emerges.

STRONG EVIDENCE: The treatment has been demonstrated to be effective and safe, either through a robust clinical trial or widespread use by doctors. The strongest trials are randomized controlled trials, in which some people get a treatment and others get a placebo.

PROMISING EVIDENCE: Early evidence from studies on patients suggests effectiveness, but more research is needed. This category includes treatments that have shown improvements in morbidity, mortality and recovery in retrospective studies, which look at existing datasets rather than starting a new trial.

TENTATIVE OR MIXED EVIDENCE: Some treatments show promising results in cells or animals, which need to be confirmed in people. Other treatments have produced different results in different experiments, raising the need for larger, more rigorously designed studies to clear up the confusion.

NOT PROMISING: These treatments show mixed evidence that suggests that they do not work.

INEFFECTIVE AND POSSIBLY HARMFUL: These treatments were once seriously considered for Covid-19 but have not held up under scientific scrutiny, proving to be ineffective or even harmful.

PSEUDOSCIENCE OR FRAUD: These are not treatments that researchers have ever considered using for Covid-19. Experts have warned against trying them, because they do not help against the disease and can instead be dangerous. Some people have even been arrested for their false promises of a Covid-19 cure.

No results at this time. Future updates may use this category.

Blocking the Virus

Antivirals can stop viruses such as H.I.V. and hepatitis C from hijacking our cells. Scientists are searching for antivirals that work against the new coronavirus.

STRONG EVIDENCE

EMERGENCY USE AUTHORIZATION


Remdesivir

Remdesivir, made by Gilead Science, was the first drug to get emergency authorization from the F.D.A. for use on Covid-19. It stops viruses from replicating by inserting itself into new viral genes. Remdesivir was originally tested as an antiviral against Ebola and Hepatitis C, only to deliver lackluster results. But preliminary data from trials that began this spring suggested the drug can reduce the hospital stays of people with severe cases of Covid-19 from 15 to 11 days. These early results did not show any effect on mortality, though retrospective data released in July hints that the drug might reduce death rates among those who are very ill.

TENTATIVE OR MIXED EVIDENCE


Favipiravir

Originally designed to beat back influenza, favipiravir blocks a virus’s ability to copy its genetic material. A small study in March indicated the drug might help purge the coronavirus from the airway, but results from larger, well-designed clinical trials are still pending.

TENTATIVE OR MIXED EVIDENCE


EIDD-2801

Another antiviral originally designed to fight the flu, EIDD-2801 has had promising results against the new coronavirus in studies in cells and on animals. It is still being tested in humans.

TENTATIVE OR MIXED EVIDENCE


Recombinant ACE-2

To enter cells, the coronavirus must first unlock them — a feat it accomplishes by latching onto a human protein called ACE-2. Scientists have created artificial ACE-2 proteins which might be able to act as decoys, luring the coronavirus away from vulnerable cells. Recombinant ACE-2 proteins have shown promising results in experiments on cells, but not yet in animals or people.

NOT PROMISING


Lopinavir and ritonavir

Twenty years ago, the F.D.A. approved this combination of drugs to treat H.I.V. Recently, researchers tried them out on the new coronavirus and found that they stopped the virus from replicating. But clinical trials in patients proved disappointing. In early July, the World Health Organization suspended trials on patients hospitalized for Covid-19. But they didn’t rule out studies to see if the drugs could help patients not sick enough to be hospitalized, or to prevent people exposed to the new coronavirus from falling ill. The drug could also still have a role to play in certain combination treatments.

NOT PROMISING


Hydroxychloroquine and chloroquine

German chemists synthesized chloroquine in the 1930s as a drug against malaria. A less toxic version, called hydroxychloroquine, was invented in 1946, and later was approved for other diseases such as lupus and rheumatoid arthritis. At the start of the Covid-19 pandemic, researchers discovered that both drugs could stop the coronavirus from replicating in cells. Since then, they’ve had a tumultuous ride through the first few months of the pandemic. A few small studies on patients offered some hope that hydroxychloroquine could treat Covid-19. The World Health Organization launched a randomized clinical trial in March to see if it was indeed safe and effective for Covid-19, as did Novartis and a number of universities.

Meanwhile, President Trump repeatedly promoted hydroxychloroquine at press conferences, touting it as a “game changer,” and even took it himself. The F.D.A. temporarily granted hydroxychloroquine emergency authorization for use in Covid-19 patients — which a whistleblower later claimed was the result of political pressure. In the wake of the drug’s newfound publicity, demand spiked, resulting in shortages for people who rely on hydroxychloroquine as a treatment for other diseases.

When data emerged from the randomized clinical trials, the message was clear: hydroxychloroquine didn’t help people with Covid-19 get better or prevent healthy people from contracting the coronavirus. (One large-scale study that concluded the drug was harmful as well was later retracted.) The World Health Organization, the National Institutes of Health and Novartis have since halted trials investigating hydroxychloroquine as a treatment for Covid-19, and the F.D.A. revoked its emergency approval. The F.D.A. now warns that the drug can cause a host of serious side effects to the heart and other organs when used to treat Covid-19.

In July, researchers at Henry Ford hospital in Detroit published a study finding that hydroxychloroquine reduced mortality in Covid-19 patients. President Trump praised the study on Twitter, but experts raised doubts about it because it was not a randomized controlled trial. Still, the White House has initiated a push for the F.D.A. to reauthorize hydroxychloroquine as an emergency Covid-19 treatment.

Despite negative results, a number of hydroxychloroquine trials have continued. A recent analysis by STAT and Applied XL found more than 180 ongoing clinical trials testing hydroxychloroquine or chloroquine, for treating or preventing Covid-19. Although it’s clear the drugs are no panacea, it’s possible they could work in combination with other treatments, or when given in early stages of the disease.

Mimicking the Immune System

Most people who get Covid-19 successfully fight off the virus with a strong immune response. Drugs might help people who can’t mount an adequate defense.

PROMISING EVIDENCE

EMERGENCY USE AUTHORIZATION


Convalescent plasma

A century ago, doctors filtered plasma from the blood of recovered flu patients. So-called convalescent plasma, rich with antibodies, helped people sick with flu fight their illness. Now researchers are trying out this strategy on Covid-19. Early trials with convalescent plasma have yielded promising, if preliminary, results, and the F.D.A. has authorized its use on very sick patients infected by the coronavirus.

TENTATIVE OR MIXED EVIDENCE


REGN-COV2 and other monoclonal antibodies

Convalescent plasma contains a mix of different antibodies, some of which can attack the coronavirus, and some of which can’t. Researchers have been sifting through the slurry for the most potent antibodies against Covid-19. Synthetic copies of these molecules, known as monoclonal antibodies, can be manufactured in bulk and then injected into patients. Safety trials for this treatment have only just begun, with several more on the way.

TENTATIVE OR MIXED EVIDENCE


Interferons

Interferons are molecules our cells naturally produce in response to viruses, rousing the immune system to attack. Injecting synthetic interferons is now a standard treatment for a number of immune disorders. Rebif, for example, is prescribed for multiple sclerosis. Early studies, including experiments in mice and cells, hint that injecting interferons may help against Covid-19. There’s even some evidence that the molecules could help prevent healthy people from getting infected.

Putting Out Friendly Fire

The most severe symptoms of Covid-19 are the result of the immune system’s overreaction to the virus. Scientists are testing drugs that can rein in its attack.

STRONG EVIDENCE


Dexamethasone

This cheap and widely available steroid blunts many types of immune responses. Doctors have long used it to treat allergies, asthma and inflammation. In June, it became the first drug shown to reduce Covid-19 deaths. That study of more than 6,000 people, which has not yet been published in a scientific journal, found that dexamethasone reduced deaths by one-third in patients on ventilators, and by one-fifth in patients on oxygen. It may be less likely to help — and may even harm — patients who are at an earlier stage of Covid-19 infections, however. In its Covid-19 treatment guidelines, the National Institutes of Health recommends only using dexamethasone in patients with COVID-19 who are on a ventilator or are receiving supplemental oxygen.

PROMISING EVIDENCE

EMERGENCY USE AUTHORIZATION


Cytosorb

Cytosorb is a cartridge that filters immune-signalling molecules called cytokines from the blood. Although cytokines are essential for fighting off diseases, they can sometimes trigger a runaway response. The body produces so much inflammation that it damages itself. By removing excess cytokines, Cytosorb may be able to cool this so-called cytokine storm. The machine can purify a patient’s entire blood supply about 70 times in a 24-hour period. It was granted emergency use authorization by the F.D.A. for Covid-19 after reports in March suggested that it had helped dozens of severely ill Covid-19 patients in Europe and China. Many clinical trials evaluating the device’s effectiveness against Covid-19 are now underway.

TENTATIVE OR MIXED EVIDENCE


Cytokine Inhibitors

Researchers have created a number of drugs that can potentially halt cytokine storms, and have proven effective against arthritis and other inflammatory disorders. Some turn off the supply of molecules that launch the production of the cytokines themselves. Others block the receptors on immune cells to which cytokines would normally bind. A few block the cellular messages they send. Against the coronavirus, several of these drugs, including tocilizumab, sarilumab and anakinra, have offered modest help in some trials, but faltered in others. The drug company Regeneron recently announced that a branded version of sarilumab, Kevzara, failed Phase 3 clinical trials.

TENTATIVE OR MIXED EVIDENCE


Stem cells

Certain kinds of stem cells can secrete anti-inflammatory molecules. Over the years, researchers have tried to use them as a treatment for cytokine storms, and now dozens of clinical trials are under way to see if they can help patients with Covid-19. But these stem cell treatments haven’t worked well in the past, and it’s not clear yet if they’ll work against the coronavirus.

Assisting Our Bodies

Caregivers can physically adjust a patient’s body to help weather Covid-19.

STRONG EVIDENCE


Prone positioning

The simple act of flipping Covid-19 patients onto their bellies opens up the lungs. The maneuver has become commonplace in hospitals around the world since the start of the pandemic. It might help some individuals avoid the need for ventilators entirely. The treatment’s benefits continue to be tested in a range of clinical trials.

STRONG EVIDENCE

EMERGENCY USE AUTHORIZATION


Ventilators and other respiratory support devices

Devices that help people breathe are an essential tool in the fight against deadly respiratory illnesses. Some patients do well if they get an extra supply of oxygen through the nose or via a mask connected to an oxygen machine. Patients in severe respiratory distress may need to have a ventilator breathe for them until their lungs heal. Doctors are divided about how long to treat patients with noninvasive oxygen before deciding whether or not they need a ventilator. Not all Covid-19 patients who go on ventilators survive, but the devices are thought to be lifesaving in many cases.

Undoing the Damage

Covid-19 can harm not just the lungs, but other parts of the body. Researchers are searching for ways to block or reverse this devastation.

STRONG EVIDENCE


Enoxaparin and other anticoagulants

The coronavirus can invade cells in the lining of blood vessels, leading to tiny clots that can cause strokes and other serious harm. Breaking up these clots with anticoagulants, which have long been used on patients with various heart conditions, improves the prospects of seriously ill patients. Early data has linked the use of anticoagulants to survival among Covid-19 patients, and many clinical trials teasing out this relationship are now underway.

PROMISING EVIDENCE


Renal replacement therapy

About one in five people with Covid-19 who are admitted to the ICU suffer from acute kidney injury. It’s not clear yet why — possibilities include the coronavirus infecting kidney cells or the immune system attacking the kidneys with a cytokine storm. In its guidelines for treating Covid-19, the National Institutes recommends filtering toxins from the blood with dialysis or other forms of renal replacement therapy. But they warn that few studies have yet been carried out to determine the best treatment for damaged kidneys.

Pseudoscience and Fraud

False claims about Covid-19 cures abound. The F.D.A. maintains a list of more than 80 fraudulent Covid-19 products, and the W.H.O. debunks many myths about the disease.

WARNING: DO NOT DO THIS


Drinking or injecting bleach and disinfectants

In April, President Trump suggested that disinfectants such as alcohol or bleach might be effective against the coronavirus if directly injected into the body. His comments were immediately refuted by health professionals and researchers around the world — as well as the makers of Lysol and Clorox. Ingesting disinfectant would not only be ineffective against the virus, but also hazardous — possibly even deadly. In July, Federal prosecutors charged four Florida men with marketing bleach as a cure for COVID-19.

WARNING: NO EVIDENCE


UV light

President Trump also speculated about hitting the body with “ultraviolet or just very powerful light.” Researchers have used UV light to sterilize surfaces, including killing viruses, in carefully managed laboratories. But UV light would not be able to purge the virus from within a sick persons’ body. This kind of radiation can also damage the skin. Most skin cancers are a result of exposure to the UV rays naturally present in sunlight.

WARNING: NO EVIDENCE


Silver

The F.D.A. has threatened legal action against a host of people claiming silver-based products are safe and effective against Covid-19 — including televangelist Jim Bakker and InfoWars host Alex Jones. Several metals do have natural antimicrobial properties. But products made from them have not been shown to prevent or treat the coronavirus.

Treatment ratings will be updated as new evidence emerges. We cannot list every possible treatment. For more details on evaluating treatments, see the N.I.H. Covid-19 Treatment Guidelines.

Tracking the Coronavirus

Note: The tracker rates individual treatments, but doctors are also testing a number of combination treatments.

Sources: National Library of Medicine; National Institutes of Health; Paul Knoepfler, University of California, Davis; Phyllis Tien, University of California, San Francisco; John Moore and Douglas Nixon, Weill Cornell Medical College.

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HIV treatment found to have no benefit for hospitalised … http://virusreports.net/hiv-treatment-found-to-have-no-benefit-for-hospitalised/ http://virusreports.net/hiv-treatment-found-to-have-no-benefit-for-hospitalised/#respond Mon, 29 Jun 2020 21:20:57 +0000 https://virusreports.net/hiv-treatment-found-to-have-no-benefit-for-hospitalised/ (Adds quote, detail, background) LONDON, June 29 (Reuters) - A combination of antiviral drugs used to treat HIV had no beneficial effect in patients hospitalised with COVID-19 in a large-scale randomised trial, British scientists said on Monday. Scientists running the RECOVERY trial at the University of Oxford said that the results "convincingly rule out any…

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(Adds quote, detail, background)

LONDON, June 29 (Reuters) – A combination of antiviral drugs used to treat HIV had no beneficial effect in patients hospitalised with COVID-19 in a large-scale randomised trial, British scientists said on Monday.

Scientists running the RECOVERY trial at the University of Oxford said that the results “convincingly rule out any meaningful mortality benefit of lopinavir-ritonavir in the hospitalised COVID-19 patients we studied.”

The scientists found no difference in mortality, length of hospital stay or the risk of being put on a ventilator, when they compared 1,596 patients given lopinavir-ritonavir with 3,376 patients in a control group.

AbbVie Inc’s Kaletra is a combination of the drugs lopinavir and ritonavir, used together to fight HIV. The company had increased its supplies while it was determining whether it can be used to treat COVID-19.

“These preliminary results show that for patients hospitalised with COVID-19 and not on a ventilator, lopinavir-ritonavir is not an effective treatment,” Peter Horby, chief investigator for the trial, said.

The scientists were unable to draw conclusions about the effectiveness of the drug combination in patients on ventilators because of the difficulty of administering it.

Lopinavir-ritonavir is also being studied in a trial by the World Health Organization.

The Oxford-based RECOVERY trial has been examining the effectiveness of six possible COVID-19 treatments, enrolling 11,800 patients in all.

The arm of the trial studying dexamethasone, a steroid, found it reduced the death rate of patients that required oxygen. Another arm found the malaria drug hydroxychloroquine, touted by U.S. President Donald Trump, had no benefit. (Reporting by Alistair Smout Editing by Franklin Paul and Peter Graff)

Our Standards: The Thomson Reuters Trust Principles.

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What is the treatment for COVID-19 patients? Montgomery doctor explains http://virusreports.net/what-is-the-treatment-for-covid-19-patients-montgomery-doctor-explains/ http://virusreports.net/what-is-the-treatment-for-covid-19-patients-montgomery-doctor-explains/#respond Sat, 27 Jun 2020 09:21:00 +0000 https://virusreports.net/what-is-the-treatment-for-covid-19-patients-montgomery-doctor-explains/ By Ashley Bowerman | June 26, 2020 at 9:09 PM CDT - Updated June 26 at 10:26 PM MONTGOMERY, Ala. (WSFA) - Most people who get diagnosed with COVID-19 will be able to recover at home. But what is it like for those that end up in the hospital? Montgomery-area pulmonologist Dr. William Saliski said…

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By Ashley Bowerman | June 26, 2020 at 9:09 PM CDT – Updated June 26 at 10:26 PM

MONTGOMERY, Ala. (WSFA) – Most people who get diagnosed with COVID-19 will be able to recover at home. But what is it like for those that end up in the hospital?

Montgomery-area pulmonologist Dr. William Saliski said treatment for COVID-19 in the United States, and across the world, is anecdotal. He says they rely on constant information from credible sources like the American Thoracic Society and the American College of Chest Physicians for continuous treatment information.

“Anyone that we feel is credible we read,” said Saliski. “Then we try to make our own decisions based on what they say. However, there is a huge amount of information that comes across daily that changes. So, we really have to make our own decisions locally.”

Without a specific treatment or vaccine existent for COVID-19, doctors and nurses are doing everything they can to help patients heal.

Saliski said this is how he is treating his COVID-19 patients. Some of his partners might do things differently.

Oxygen therapy and Prone Positioning

“Patients that are not critically ill, that are in a regular room, who have low-grade COVID pneumonitis, they are coughing and somewhat short of breath. Of course, oxygen therapy is paramount,” Saliski said.

There are various forms of oxygenation being used.

“If someone does go into Adult Respiratory Distress Syndrome, then we have parameters that we follow for Adult Respiratory Distress Syndrome on how we ventilate patients,” Saliski said.

He said they try to refrain from using a BiPAP machine because that machine aerosolizes the virus in rooms and it puts healthcare workers at risk.

Along with oxygen therapy, a process called “prone positioning” is also used. Prone positioning involves frequently turning a patient over on their stomach to increase airflow to different areas of a patient’s lungs, hopefully preventing the need for ventilation.

“It is one of the bedrock treatments for this disease,” Saliski said. “What happens is by proning somebody, you flip them over on their stomach, this disease process then, it’s called ‘atelectasis’ or collapse of the lung, then will settle out from one side of the lung to the other side and as it does that your oxygenation improves.”

He said proning is used on patients that are intubated, on a mechanical ventilator, and for patients receiving oxygen therapy at home.

The cytokine storm – treatment before it’s too late

More severely symptomatic COVID-19 patients are experiencing what Dr. Saliski called a “cytokine storm.”

This is where a patient’s blood is teeming with high levels of immune system proteins called “cytokines.” Scientists believe these cytokines are evidence that the body is beginning to attack its own cells and tissues instead of fighting the virus.

“Basically what happens is the virus turns the immune system on and the body is in a storm state where organs are attacked. Primarily lung, but it can be kidney, heart, any part of the body,” Saliski said. “What we are trying to do is prevent that storm from occurring.”

This is why Saliski said, “timing of this disease for treatment is extremely important. A lot of the medications that we’re giving, we’re timing so that that storm does not occur.”

The storm causes inflammation that he says is being treated with steroids.

“A recent study came out with the use of what’s called ‘Dexamethasone,’ which is a steroid, and we’re using that early on in the disease process to try to prevent further inflammatory storm,” Saliski said.

Another drug called “Actemra,” an IL-6 inhibitor, is also being used to help prevent the cytokine storm.

“We feel that this disease process causes one to be what’s called ‘hypercoagulable,’ where the blood thickens, creating a clot in the venous system breaking off from the leg to the lungs causing a pulmonary embolism,” Salsiki said.

A pulmonary embolism, or sudden blockage in the lung artery, is life-threatening. That is why they are giving some patients blood thinners to prevent the blood clots from happening.

“Early anticoagulation will prevent blood from clotting, said Saliski. “What degree of anticoagulation depends on how sick the patient is.”

Convalescent plasma, or the blood from those who have already fought and recovered from COVID-19, is being given to sick patients in an effort to help build the immune system.

“That’s plasma that has been taken from patients who have already had COVID-19, and they have developed antibodies and what we’re doing is taking that plasma and giving it to other patients who have similar blood types, and it’s basically boosting their immune system with antibodies that have been made by someone else,” said Saliski. “That has been given across the board early to late with variable response.”

“When we give someone convalescent plasma, it’s like giving them a vaccine in a respect that we are revving their immune system to protect them from getting this virus,” Saliski said.

Salsiki said they are also continuing to use the FDA approved antiviral drug Remdesivir when needed.

“I feel it has been effective, but again it’s the timing of when you give it,” said Saliski. “I feel like if somebody is already on the ventilator with severe disease and multisystem organ failure it’s less effective.”

“We don’t know the exact time frame of a vaccine. I don’t think anyone does,” Saliski said. “But I do know multiple companies are working super overtime to get this vaccine out.”

Saliski said he believes a vaccine will be developed in the next six to eight months.

“I am a huge advocate of vaccines for all viruses. I believe that we were able to eradicate some horrific diseases in the past like polio, measles, etc,” said Saiski. “This is no different.”

“I think everyone, everyone, should get this vaccine,” Saliski said.

Copyright 2020 WSFA 12 News. All rights reserved.

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Potential treatment for COVID-19 patients’ respiratory distress identified in new study http://virusreports.net/potential-treatment-for-covid-19-patients-respiratory-distress-identified-in-new-study/ http://virusreports.net/potential-treatment-for-covid-19-patients-respiratory-distress-identified-in-new-study/#respond Tue, 09 Jun 2020 01:21:34 +0000 https://virusreports.net/potential-treatment-for-covid-19-patients-respiratory-distress-identified-in-new-study/ Early data from a clinical study suggest that an off-label cancer drug provided clinical benefit to a small group of patients with severe COVID-19.The cancer drug acalabrutinib, which blocks the Bruton tyrosine kinase (BTK) protein and is approved to treat some blood cancers, was associated with reduced respiratory distress and a reduction in the overactive…

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Early data from a clinical study suggest that an off-label cancer drug provided clinical benefit to a small group of patients with severe COVID-19.

The cancer drug acalabrutinib, which blocks the Bruton tyrosine kinase (BTK) protein and is approved to treat some blood cancers, was associated with reduced respiratory distress and a reduction in the overactive immune response in most of the treated patients, according to the study published Friday in Science Immunology.

Researchers caution that the findings should not be considered clinical advice but that they are being shared to assist with the public health response to the coronavirus pandemic.

BTK inhibitors are not approved for treatment of COVID-19; their potential must be tested in a randomized, controlled clinical trial, scientists said.

KAWASAKI-LIKE SYNDROME LINKED TO COVID-19 IN CHILDREN IS NEW CONDITION, STUDY REVEALS

A new study reveals an off-label cancer drug could provide benefits to people with severe COVID-19 symptoms.

A new study reveals an off-label cancer drug could provide benefits to people with severe COVID-19 symptoms.
(iStock)

The BTK protein is involved with macrophages, a type of innate immune cell that can cause inflammation by producing proteins known as cytokines, which help to stiumulate the body’s immune response.

“In some patients with severe COVID-19, a large amount of cytokines are released in the body all at once, causing the immune system to damage the function of organs such as the lungs, in addition to attacking the infection,” according to a summary of the study’s findings.

COVID-19 APPS POSE PRIVACY RISKS TO USERS WORLDWIDE, INVESTIGATION FINDS

This study included 19 patients with a confirmed COVID-19 diagnosis that required hospitalization, as well as with imflammation and low blood-oxygen levels.

Researchers in the Center for Cancer Research at the National Cancer Institute (NCI), in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), as well as the U.S. Department of Defense’s Walter Reed National Military Medical Center, and four other hospitals nationally, were involved in the study.

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Remdesivir for the Treatment of Covid-19 — Preliminary Report http://virusreports.net/remdesivir-for-the-treatment-of-covid-19-preliminary-report/ http://virusreports.net/remdesivir-for-the-treatment-of-covid-19-preliminary-report/#respond Fri, 22 May 2020 23:21:27 +0000 https://virusreports.net/remdesivir-for-the-treatment-of-covid-19-preliminary-report/ 14 ReferencesRelated ArticlesAbstract BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either…

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Abstract

Background

Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.

Methods

We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.

Results

A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).

Conclusions

Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.)

Introduction

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in December 2019 as the cause of a respiratory illness designated coronavirus disease 2019, or Covid-19.1 Several therapeutic agents have been evaluated for the treatment of Covid-19, but none have yet been shown to be efficacious.2,3 Remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase with inhibitory activity against SARS-CoV and the Middle East respiratory syndrome (MERS-CoV),4-7 was identified early as a promising therapeutic candidate for Covid-19 because of its ability to inhibit SARS-CoV-2 in vitro.8 In addition, in nonhuman primate studies, remdesivir initiated 12 hours after inoculation with MERS-CoV9,10 reduced lung virus levels and lung damage.

To evaluate the clinical efficacy and safety of putative investigational therapeutic agents among hospitalized adults with laboratory-confirmed Covid-19, we designed an adaptive platform to rapidly conduct a series of phase 3, randomized, double-blind, placebo-controlled trials. Here, we describe the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACTT-1), in which we evaluated treatment with remdesivir as compared with placebo.

Methods

Design

Enrollment for ACTT-1 began on February 21, 2020, and ended on April 19, 2020. There were 60 trial sites and 13 subsites in the United States (45 sites), Denmark (8), the United Kingdom (5), Greece (4), Germany (3), Korea (2), Mexico (2), Spain (2), Japan (1), and Singapore (1). Eligible patients were randomly assigned in a 1:1 ratio to receive either remdesivir or placebo. Randomization was stratified by study site and disease severity at enrollment (see the Supplementary Appendix, available with the full text of this article at NEJM.org, for details about stratification criteria). Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 through 10 or until hospital discharge or death. A matching placebo was administered according to the same schedule and in the same volume as the active drug. A normal saline placebo was used at the European sites and at some non-European sites owing to a shortage of matching placebo; the infusions were masked with an opaque bag and tubing covers to maintain blinding. All patients received supportive care according to the standard of care for the trial site hospital. If a hospital had a written policy or guideline for use of other treatments for Covid-19, patients could receive those treatments. In the absence of a written policy or guideline, other experimental treatment or off-label use of marketed medications intended as specific treatment for Covid-19 were prohibited from day 1 through day 29 (though such medications could have been used before enrollment in this trial).

The trial protocol was approved by the institutional review board at each site (or by a centralized institutional review board as applicable) and was overseen by an independent data and safety monitoring board. Informed consent was obtained from each patient or from the patient’s legally authorized representative if the patient was unable to provide consent. Full details of the trial design, conduct, oversight, and analyses can be found in the protocol and statistical analysis plan (available at NEJM.org).

Procedures

Patients were assessed daily during their hospitalization, from day 1 through day 29. The patient’s clinical status on an eight-category ordinal scale (defined below) and the National Early Warning Score was recorded each day.11,12 All serious adverse events and grade 3 or 4 adverse events that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions were recorded. (See the full description of trial procedures in the Supplementary Appendix.)

Statistical Analysis

The primary analysis was a stratified log-rank test of the time to recovery with remdesivir as compared with placebo, with stratification by disease severity. (See the Supplementary Appendix for more information about the planned statistical analysis.)

The primary outcome measure was the time to recovery, defined as the first day, during the 28 days after enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category ordinal scale. The categories are as follows: 1, not hospitalized, no limitations of activities; 2, not hospitalized, limitation of activities, home oxygen requirement, or both; 3, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control reasons); 4, hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (Covid-19–related or other medical conditions); 5, hospitalized, requiring any supplemental oxygen; 6, hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7, hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8, death. Other outcomes included mortality at 14 and 28 days after enrollment and grade 3 and 4 adverse events and serious adverse events that occurred during the trial. Prespecified subgroups in these analyses were defined according to sex, disease severity (as defined for stratification and by ordinal scale at enrollment), age (18 to 39 years, 40 to 64 years, or 65 years of age or older), and duration of symptoms before randomization (≤10 days or >10 days). (See the protocol for more information about the trial methods.)

The primary outcome was initially defined as the difference in clinical status, defined by the eight-category ordinal scale, among patients treated with remdesivir as compared with placebo at day 15. This initial primary outcome became the key secondary outcome after the change in primary outcome. The change was proposed on March 22, 2020, by trial statisticians who were unaware of treatment assignments and had no knowledge of outcome data. When this change was proposed, 72 patients had been enrolled and no interim data were available. The amendment was finalized on April 2, 2020, without any knowledge of outcome data from the trial and before any interim data were available. This change in primary outcome was made in response to evolving information, external to the trial, indicating that Covid-19 may have a more protracted course than previously appreciated.

On April 27, 2020, the data and safety monitoring board reviewed results. Although this review was originally planned as an interim analysis, because of the rapid pace of enrollment, the review occurred after completion of enrollment while follow-up was still ongoing. At the time of the data and safety monitoring board report, which was based on data cutoff date of April 22, 2020, a total of 482 recoveries (exceeding the estimated number of recoveries needed for the trial) and 81 deaths had been entered in the database. At that time, the data and safety monitoring board recommended that the preliminary primary analysis report and mortality data from the closed safety report be provided to trial team members from the National Institute of Allergy and Infectious Diseases (NIAID). These results were subsequently made public; the treating physician could request to be made aware of the treatment assignment of patients who had not completed day 29 if clinically indicated (e.g., because of worsening clinical status), and patients originally in the placebo group could be given remdesivir. This report summarizes the preliminary results from this ongoing trial.

Results

Patients

Figure 1. Figure 1. Enrollment and Randomization.

Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization; 541 were assigned to the remdesivir group and 522 to the placebo group (Figure 1). Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Forty-nine patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death (36 patients) or because the patient withdrew consent (13). Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2).

As of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had completed the trial through day 29, recovered, or died. Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were 132 patients in the remdesivir group and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit. The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available at the time of the database freeze.

Table 1. Table 1. Demographic and Clinical Characteristics at Baseline.

The mean age of patients was 58.9 years, and 64.3% were male (Table 1). On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported; 249 (23.4%) were Hispanic or Latino. Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%).

The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix; 272 (25.6%) patients met category 7 criteria on the ordinal scale, 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4. There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group.

Primary Outcome

Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries.

Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen; Panel B), in those with a baseline score of 5 (receiving oxygen; Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation; Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation or ECMO; Panel E).

Table 2. Table 2. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3. Figure 3. Time to Recovery According to Subgroup.

The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.

Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days; rate ratio for recovery, 1.32; 95% confidence interval [CI], 1.12 to 1.55; P<0.001; 1059 patients (Figure 2 and Table 2). Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84); among patients with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7; 272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.31; 95% CI, 1.12 to 1.54; 1017 patients). Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 to 1.57; 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81; 380 patients) (Figure 3).

Key Secondary Outcome

The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50; 95% CI, 1.18 to 1.91; P=0.001; 844 patients) (Table 2 and Fig. S5). Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04; 1059 patients). The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2). The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10).

Safety Outcomes

Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3); 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients). Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators.

Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4). The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group); acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]); pyrexia (27 events [5.0%], as compared with 17 [3.3%]); hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]); and increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.

Discussion

Preliminary results of this trial suggest that a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with Covid-19. This benefit was seen in the number of days to recovery (median, 11 days, as compared with 15; rate ratio for recovery, 1.32 [95% CI, 1.12 to 1.55]) and in recovery according to the ordinal scale score at day 15 (odds ratio, 1.50; 95% CI, 1.18 to 1.91). Even though the trial was ongoing, the data and safety monitoring board made the recommendation to unblind the results to the trial team members from the NIAID, who subsequently decided to make the results public. Given the strength of the results about remdesivir, these findings were deemed to be of immediate importance for the care of patients still participating in the trial as well as for those outside the trial who might benefit from treatment with remdesivir.

The benefit was most apparent in patients with a baseline ordinal score of 5 (requiring oxygen), a finding most likely due to the larger sample size in this category (since the interaction test of treatment by baseline score on the ordinal scale was not significant). Confidence intervals for baseline ordinal scores of 4 (not receiving oxygen), 6 (receiving high-flow oxygen), and 7 (receiving ECMO or mechanical ventilation) are wide. We note that the median recovery time for patients in category 7 could not be estimated, which suggests that the follow-up time may have been too short to evaluate this subgroup. Additional analyses of outcomes such as the time to a one- or two-point improvement on the ordinal scale score will be conducted after the full cohort has completed 28 days of follow-up and may provide additional insight into the treatment of this critical subgroup. Our findings highlight the need to identify Covid-19 cases and start antiviral treatment before the pulmonary disease progresses to require mechanical ventilation.

The findings in our trial should be compared with those observed in a randomized trial from China in which 237 patients were enrolled (158 assigned to remdesivir and 79 to placebo).13 The time to clinical improvement, defined as the time to a two-point improvement in the score on the ordinal scale, was 21.0 days (95% CI, 13.0 to 28.0) in the remdesivir group and 23.0 days (95% CI, 15.0 to 28.0) in the control group, with a hazard ratio (for clinical improvement) of 1.23 (95% CI, 0.87 to 1.75). The six-category ordinal scale used in that trial yielded a common odds ratio for improvement in the ordinal score scale of 1.25 (95% CI, 0.76 to 2.04) at day 14. That trial failed to complete full enrollment (owing to the end of the outbreak), had lower power than the present trial (owing to the smaller sample size and a 2:1 randomization), and was unable to demonstrate any statistically significant clinical benefits of remdesivir.

The primary outcome of the current trial was changed with protocol version 3 on April 2, 2020, from a comparison of the eight-category ordinal scale scores on day 15 to a comparison of time to recovery up to day 29. Little was known about the natural clinical course of Covid-19 when the trial was designed in February 2020. Emerging data suggested that Covid-19 had a more protracted course than was previously known, which aroused concern that a difference in outcome after day 15 would have been missed by a single assessment at day 15. The amendment was proposed on March 22, 2020, by trial statisticians who were unaware of treatment assignment and had no knowledge of outcome data; when this change was proposed 72 patients had been enrolled. Although changes in the primary outcome are not common for diseases that are well understood, it is recognized that in some trials, such as those involving poorly understood diseases, circumstances may require a change in the way an outcome is assessed or may necessitate a different outcome.14 The original primary outcome became the key secondary end point. In the end, findings for both primary and key secondary end points were significantly different between the remdesivir and placebo groups.

Numerous challenges were encountered during this trial. The trial was implemented during a time of restricted travel, and hospitals restricted the entrance of nonessential personnel. Training, site initiation visits, and monitoring visits often were performed remotely. Research staff were often assigned other clinical duties, and staff illnesses strained research resources. Many sites did not have adequate supplies of personal protective equipment and trial-related supplies, such as swabs. However, research teams were motivated to find creative solutions to overcome these challenges.

The Food and Drug Administration has made remdesivir available under an emergency-use authorization for the treatment of adults and children with severe Covid-19 disease. Our preliminary report is intended to help inform clinicians considering the use of remdesivir. We are awaiting final visits, data entry, monitoring, and data lock for the last of the 1063 patients enrolled, after which an update of the results will be provided. To ensure the accuracy of the reported findings, we evaluated the primary outcome, key secondary outcomes, and mortality results on current data from May 18, 2020. The results were similar to those reported in the Results section of this article. The full statistical analysis of the entire trial population must occur, in order to fully understand the efficacy of remdesivir in this trial.

These preliminary findings support the use of remdesivir for patients who are hospitalized with Covid-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.

Funding and Disclosures

The trial was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. This trial has been funded in part with federal funds from the NIAID and the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program. This trial has been supported in part by the NIAID of the NIH under award numbers UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689. The trial has also been funded in part by the governments of Japan, Mexico, Denmark, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC_UU_12023/23).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, the Departments of the Army, Navy, or Air Force, the Department of Defense, or the Department of Veterans Affairs, nor does any mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Gilead Sciences provided remdesivir for use in this trial but did not provide any financial support. Employees of Gilead Sciences participated in discussions about protocol development and in weekly protocol team calls. The NIAID ultimately made all decisions regarding trial design and implementation.

This article was published on May 22, 2020, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank the members of the ACTT-1 Study Group (see the Supplementary Appendix) for their many contributions in conducting the trial, the members of the Data and Safety Monitoring Board (Michael G. Ison, M.D. [Chair], Northwestern University Feinberg School of Medicine; Nina Singh, M.D., University of Pittsburgh; Bernd Salzberger, M.D., Ph.D., University of Regensburg; Wendy Leisenring, Sc.D., Fred Hutchinson Cancer Research Center; and Peter Sasieni, Ph.D., King’s College London) for their oversight, and the patients themselves for their altruism in participating in this trial.

Author Affiliations

From the National Institute of Allergy and Infectious Diseases, National Institutes of Health (J.H.B., K.M.T., L.E.D., S.N., H.C.L.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick (T. Bonnett), and Emmes, Rockville (M.G., M.M.) — all in Maryland; Emory University, Atlanta (A.K.M.); Montefiore Medical Center–Albert Einstein College of Medicine (B.S.Z.) and NYU Langone Health and NYC Health + Hospitals– Bellevue (K.D.), New York; University of Nebraska Medical Center, Omaha (A.C.K., M.G.K.); Massachusetts General Hospital, Boston (E.H.), and University of Massachusetts Medical School, Worcester (R.W.F.); University of Washington, Seattle (H.Y.C.), and Evergreen Health Medical Center, Kirkland (D.L.C.) — both in Washington; University of California, San Francisco, San Francisco (A.L.), Cedars Sinai Medical Center, Los Angeles (V.T.), University of California, Irvine, Irvine (L.H.), University of California, San Diego, La Jolla (D.A.S.), and Gilead Sciences, Foster City (A.O.) — all in California; University of Minnesota (S.K.) and University of Minnesota, School of Public Health and INSIGHT (J.D.N.), Minneapolis; University of Texas Health San Antonio, University Health System, and the South Texas Veterans Health Care System, San Antonio (T.F.P.), and Baylor College of Medicine, Houston (R.L.A.); Hospital Germans Trias i Pujol & irsiCaixa AIDS Research Institute, Badalona, Spain (R.P.); University of Pennsylvania, Philadelphia (W.R.S.); Medical School, National and Kapodistrian University of Athens, Athens (G.T.); National Center for Infectious Diseases–Tan Tock Seng Hospital–Lee Kong Chian School of Medicine–Yong Loo Lin School of Medicine, Singapore, Singapore (D.C.L.); the National Center for Global Health and Medicine Hospital, Tokyo (N.O.); Seoul National University Hospital, Seoul, South Korea (M.O.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City (G.M.R.-P.); the Department of Infectious Diseases, Amager Hvidovre Hospital–University of Copenhagen, Hvidovre (T. Benfield), and Rigshospitalet, Department of Infectious Diseases (CHIP) and INSIGHT, Copenhagen (J.L.) — both in Denmark; University Hospital of Cologne, Cologne, Germany (G.F.); Vanderbilt University Medical Center, Nashville (C.B.C.); and University College London, MRC Clinical Trials Unit at UCL and INSIGHT, London (A.G.B., S.P.).

Address reprint requests to Dr. Beigel at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fishers Ln., Rm. 7E60, MSC 9826, Rockville, MD 20892-9826, or at [email protected].

A complete list of members of the ACTT-1 Study Group is provided in the Supplementary Appendix, available at NEJM.org.

Supplementary Material

References (14)

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  2. 2. Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020;382:17871799.

  3. 3. Borba MGS, Val FFA, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open 2020;3(4):e208857e208857.

  4. 4. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020;11:222222.

  5. 5. Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio 2018;9(2):e00221-18e00221-18.

  6. 6. Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res 2019;169:104541104541.

  7. 7. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017;9:eaal3653eaal3653.

  8. 8. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269271.

  9. 9. de Wit E, Rasmussen AL, Falzarano D, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A 2013;110:1659816603.

  10. 10. de Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A 2020;117:67716776.

  11. 11. Royal College of Physicians. National Early Warning Score (NEWS) 2. 2017 (https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2).

  12. 12. King JC, Beigel JH, Ison MG, et al. Clinical development of therapeutic agents for hospitalized patients with influenza: challenges and innovations. Open Forum Infect Dis 2019;6:ofz137ofz137.

  13. 13. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:15691578.

  14. 14. The CONSORT Group. 3b. Changes to trial design (http://www.consort-statement.org/consort-2010).

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Man credits treatment method that’s almost 100 years old with saving his life from COVID-19 http://virusreports.net/man-credits-treatment-method-thats-almost-100-years-old-with-saving-his-life-from-covid-19/ http://virusreports.net/man-credits-treatment-method-thats-almost-100-years-old-with-saving-his-life-from-covid-19/#respond Wed, 20 May 2020 13:22:01 +0000 https://virusreports.net/man-credits-treatment-method-thats-almost-100-years-old-with-saving-his-life-from-covid-19/ FARGO — Gene Bad Hawk’s battle with the coronavirus began with headaches and fever. Over the ensuing 20 days since his diagnosis he would bounce between motel isolation rooms and hospital beds. Before he entered the hospital the fourth time, on May 5, he called his friends and relatives and asked them to pray for…

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FARGO — Gene Bad Hawk’s battle with the coronavirus began with headaches and fever. Over the ensuing 20 days since his diagnosis he would bounce between motel isolation rooms and hospital beds.

Before he entered the hospital the fourth time, on May 5, he called his friends and relatives and asked them to pray for him.

“I thought I was going to die,” he said Tuesday, May 19.

Bad Hawk’s high fever and headaches never abated. He was nauseous, suffered from diarrhea and lost his appetite.

He threw up so often it was difficult to keep even water down. He became dehydrated and, with “no desire to eat,” lost 26 pounds.

When he was admitted to the hospital for the fourth time, his symptoms had taken a turn for the worse. He had shortness of breath and low blood-oxygen levels.

“I couldn’t catch my breath,” he said. The 57-year-old was given oxygen, but not placed on a ventilator.

Given his deteriorating condition, Bad Hawk’s doctors at Essentia Health decided he was suitable for a research trial and he readily agreed to receive what’s called convalescent plasma — blood plasma containing neutralizing antibodies from a patient who recovered from COVID-19, the disease caused by the coronavirus.

The plasma was administered by intravenous drip, along with a bacteria to fight a secondary infection, Bad Hawk said.

“I felt miserable,” he said. But also hopeful.

The next morning, he felt a little better. By the end of the day, he felt good enough to eat his first meal in 10 days. The following day, “I felt really good.”

Good enough that he soon was discharged from the hospital, on May 8. Eleven days later, he considers himself fully recovered.

“I have no symptoms,” Bad Hawk said. On Monday, he felt good enough to go for a six-mile bicycle ride.

After 14 days of being symptom free, a person who was diagnosed with COVID-19 by a polymerase chain reaction, or PCR laboratory test, and is no longer infectious might be eligible to donate blood plasma, something Bad Hawk plans to do.

He credits the plasma with immune-boosting antibodies for saving his life, along with the prayers from family members and friends in North Dakota, Minnesota and his native Montana.

“I believe God directed the doctors to administer the plasma,” he said. “Not many people receive plasma.”

Dr. Karol Kremens, director of the intensive care unit at Essentia Health and a pulmonologist, said that convalescent plasma for COVID-19 patients is an experimental treatment, given only to hospital patients with low oxygen levels.

Essentia has access to the plasma through a trial conducted by the Mayo Clinic. Although early reports are encouraging, there still is no clear proof that convalescent plasma is effective.

“It’s still under active investigation,” he said. “Hopefully as the study progresses we will have the data” to prove whether plasma is an effective treatment. “At this point we work under the assumption that it works and helps our patients.”

RELATED:

North Dakota health officials and Vitalant, the nonprofit blood bank serving hospitals in the region, encourage those who have recovered from COVID-19 to consider donating their plasma.

“There have already been a few cases in North Dakota where convalescent plasma treatment has proven beneficial for patients infected with COVID-19,” said Dr. Joan Connell, field medical officer for the North Dakota Department of Health. “This is a unique opportunity for someone who has recovered from COVID-19 to potentially save a life.”

Vitalant’s criteria for donating convalescent plasma require complete resolution of symptoms for at least 14 days, followed by a negative COVID-19 test or complete resolution of symptoms for at least 28 days, with or without a negative test result.

Also, donors must meet all other donor eligibility requirements and must be at least 16 years old, weigh at least 110 pounds and be in good general health.

Kremens also encourages those who have recovered from COVID-19 to consider donating plasma so other patients can benefit.

“We have given it to six patients at Essentia Health in Fargo,” he said. “We have seen improvement in some,” but two patients died.

Even 10 days ago, it took 48 hours for the convalescent plasma to arrive from New York City, he said. Now, through Vitalant, the plasma is available within a few hours, thanks to donors in the area.

“The more we have locally the more we are able to get it right away,” Kremens said.

Convalescent plasma, also administered by Sanford Health, is viewed as an interim treatment until other therapies or a vaccine become available. The treatment isn’t without risks, but appears generally safe.

The idea of using plasma containing antibodies from people who have recovered from an illness is not new. The method has been used for almost 100 years, with some evidence of benefit for rabies, hepatitis B, polio, measles, influenza, Ebola and other pathogens, according to the American College of Hepatology.

Bad Hawk is grateful that he was able to receive the experimental treatment, which he credits with saving his life. Before he became ill he was living in Fargo, but lately has been living in homeless shelters. He’s looking forward to returning to work soon as a day laborer.

“I feel pretty normal,” he said.

And Bad Hawk has advice for those who don’t take the risk of becoming infected seriously enough, as he did. Wear a mask, wash your hands frequently, and avoid close contact with people.

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Plasma treatment gives hope to LI COVID-19 patients http://virusreports.net/plasma-treatment-gives-hope-to-li-covid-19-patients/ http://virusreports.net/plasma-treatment-gives-hope-to-li-covid-19-patients/#respond Sun, 26 Apr 2020 15:29:06 +0000 https://virusreports.net/plasma-treatment-gives-hope-to-li-covid-19-patients/ It appears that you are trying to access our website from a location in the European Union, which enforces the General Data Protection Regulation (GDPR). Unfortunately, because of this regulation we cannot provide access at this time. We appreciate your understanding.

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