Can convalescent plasma treat coronavirus?


It is the latest development in the effort to use a 19th century treatment to help 21st century patients.

The contract with the DoD’s Joint Acquisition Task Force is to develop a new convalescent blood plasma process that makes more serum-derived products, and faster.

President Donald Trump and U.S. health leaders have filed a full court press to encourage people who have survived Covid-19 to donate plasma to help those who are ill.

Two weeks ago, on a tour of the Red Cross, Trump called on people to donate volunteer plasma “as soon as you can.”

“We have a lot of people who would heal, get better. As soon as you can, please,” Trump said.

While nearly 67,000 people are infused with the treatment and nearly 14,000 doctors use it, according to UScovidplasma.org, it is not yet clear if it works. Several studies are underway.

A Victorian solution to a modern problem?

Convalescent plasma is a treatment made from the blood of people who have recovered from an infection such as Covid-19. Plasma is the liquid part of the blood that contains immune cells and antibodies – proteins that the body makes to fight infection. The plasma can be infused into a sick person to help recovery.

Since the Victorian era, doctors have been using this treatment to combat severe cases of the flu. The treatment has also shown success with two other deadly coronaviruses – MERS and SARS. However, it will take studies to prove that it works to treat Covid-19. Other treatments absent, doctors have chosen to use the treatment because it was still being studied.

Doctors are trying the old treatment

When the Covid-19 pandemic hit New York City hard in March, doctors desperately wanted to save patients, not sure what could help. Plasma of recovered Covid-19 patients showed some early promise. For professionals accustomed to relying on scientific evidence and established facts, there was – and still is – not much to work with.

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“It was kind of learning to fly the plane when we were in the midair,” said Drs. Nicole Bouvier, a Mount Sinai infectious disease specialist. “There are basic things you know about human physiology, but you do not necessarily know how this particular virus will behave and what the best treatments are,” she said.

“We’ve probably changed what we did on a daily basis.”

To see what worked, Bouvier and team conducted a retrospective analysis on data collected from 39 patients.

Even in that small group, the convalescent plasma stood out.

Bouvier published the results in a small pre-print study, which means it has not been peer reviewed in May. Patients treated with plasma recovery improved more than those who were not transferred, and more patients survived.
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“We do not yet have definitive answers, but we are on track to get definitive answers and, I would say, the evidence, although incomplete, is promising,” Bouvier said.

Dr. Janet Woodcock, who is training therapeutic efforts under Operation Warp Speed ​​as director of the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, recently called vaccines the “permanent hope,” but said faxes are not the only approach. are that this country will recover from the Covid-19 pandemic.

Convalescent plasma, Woodcock said, is an option that “can be quite quickly possible.” Woodcock, said it is a treatment that the government is trying to speed up, even before the government knows if it is working.

First results in China

Somewhere, a handful of small studies in China looked promising.

A small study published in JAMA in March showed that four out of five patients received improved plasma. A second small study of 10 Chinese patients published in May in the journal PNAS saw improvement in patients treated with plasma recovery, without safety concerns. Two other small pre-print studies from China showed similar results.
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One additional observational study by Chinese researchers published in June saw no improvement in mortality among six critically ill patients, but the authors did not completely remove the convalescent plasma. Instead, they suggested that it might work if patients were treated earlier.

Try the treatment in the US

The U.S. Food and Drug Administration has not yet approved its use for the treatment of Covid-19, but in late March, the FDA paved the way for scientists to restore plasma with patients to try and study its effects.
Doctors at Houston Methodist immediately carried out what it says were the nation’s first plasma transfusions. They published their May issue in the American Journal of Pathology.

Among 25 patients hospitalized with Covid-19, seven days after the restorative plasma treatment, nine showed some improvement and seven were discharged from the hospital. By day 14, 19 had improved and 11 had been dismissed. There were no security issues.

However, it is not clear if the treatment was the reason these patients improved; the research results should be reproduced in a larger group of patients.

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When evidence emerged that it had shown some success, the FDA issued a call in April to restore patients to donate plasma. The government launched a website instructing Americans on how they could donate, such as the American Red Cross.

First ‘maybe’, then ‘possible’, ‘now’ likely ‘

In June, a larger study of 5,000 hospital patients published in the Journal of Clinical Investigation showed that treatment was safe.

Dr Arturo Casadevall, one of the researchers, called the recovery of plasma the “good news story” of the pandemic.

The head of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Casadevall thought the practice held promise and helped spearhead the national push to understand if this therapy works in March, when he and a colleague wrote about his capabilities in the Journal of Clinical Research and created the National Covid-19 Convalescent Plasma Project. It is a national network of providers at 57 institutions in 46 states. More than 100 people attended the group’s first conference meeting.
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The organization quickly published a manual with best practice for convalescent plasma for physicians. It created a website that collects the latest science. The doctors began clinical trials. One who is on the move is looking at the impact of treatment on health care workers. Another looks at the effect of convalescent plasma on patients who are not in the hospital.

“When we first started this attempt when you asked ‘do you think it will work?’ I would have said ‘maybe’, ” Casadevall said. “Since then I have gone to ‘possible’, and now I am at ‘likely’.”

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Casadevall wants more research to prove it works.

“To be really sure, you have to complete the randomized clinical trials,” Casadevall said. “But the good thing has been that there have been multiple reports that have been stimulating, including my clinical trials of Wuhan that had to stop prematurely.”

That trial was stopped when the flood of patients trembled after a trickle and there were not enough patients to test the therapy.

The challenges

The number of cases can also affect how much of the therapy is available. Unlike with a monoclonal antibody therapies that can be made in the lab, this treatment is dependent on volunteers.

“It’s a limited resource,” Woodcock said Monday. Therefore, there has been a compelling pressure to get more donors. Even Dwayne “The Rock” Johnson is signed up to urge people to donate.

Normally, one donor’s plasma can treat two or three people and the original donor can come back and donate within a few weeks.

But there are only so many donors, Woodcock said, and scientists are beginning to think that there is only a month-long window in which people have enough antibodies in their blood to help someone else fight the disease. But again, they need more research to know for sure.

An August study of 35,000 patients that has not yet been peer-reviewed found that people taking plasma treatment early allowed the deaths to decrease further. People who received the transfusions within three days of diagnosis had a seven-day mortality rate of 8.7%, while patients treated four or more days in the course of illness had a mortality rate of 11.9%.

But there was no placebo group. Without that comparison, it is hard to know if the treatment made the difference.

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The treatment can be difficult to get right. In contrast, monoclonal antibody treatments are performed by scientists in the lab. They choose the antibody that works best in the lab to neutralize the virus and reproduce in the lab. Such Covid-19 antibody therapies are now also in clinical trials.

With convalescent plasma, patients receive all the antibodies in that plasma, not just those carefully made to fight the virus. Each donor’s plasma is slightly different and some may have more antibodies that better protect against the virus than others.

“Convalescent plasma, I think we need to be more careful about that,” said Dr. Anthony Fauci recently. “You want to make sure you do it right.”

The pressure

Even before scientists are sure, the U.S. Department of Defense said it wants to collect 8,000 units by the end of September. Casadevall said the government also has 200,000 units, which he says is a sign that the experimental treatment is here to stay. Plasma can be stored frozen for about a year.

Woodcock, who said the U.S. government is trying to speed up these plasma drivers, thinks there could be an added benefit to convalescent plasma that is about treating someone’s symptoms.

“I think people feel very helpless in this face,” Woodcock said. “This is something that anyone who can be infected can contribute.”

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