Houston Chronicle Sunday

What did we learn from using plasma treatment?

- By Katie Thomas and Noah Weiland

Scott Cohen was on a ventilator struggling for his life with COVID-19 last April when his brothers pleaded with Plainview Hospital on Long Island to infuse him with the blood plasma of a recovered patient.

The experiment­al treatment was hard to get but was gaining attention at a time when doctors had little else. After an online petition drew 18,000 signatures, the hospital gave Cohen, a retired Nassau County medic, an infusion of the pale yellow stuff that some called “liquid gold.”

In those terrifying early months of the pandemic, the idea that antibody-rich plasma could save lives took on a life of its own before there was evidence that it worked. The Trump administra­tion, buoyed by proponents at elite medical institutio­ns, seized on plasma as a good-news story at a time when there were not many others. It awarded more than $800 million to entities involved in its collection and administra­tion and put Dr. Anthony Fauci’s face on billboards promoting the treatment.

A coalition of companies and nonprofit groups, including the Mayo Clinic, Red Cross and Microsoft, mobilized to urge donations from people who had recovered from COVID-19, enlisting celebritie­s like Samuel L. Jackson and Dwayne Johnson, the actor known as the Rock. Volunteers, some dressed in superhero capes, showed up to blood banks in droves.

Cohen, who later recovered, was one of them. He went on to donate his own plasma 11 times.

But by the end of the year, good evidence for convalesce­nt plasma had not materializ­ed, prompting many prestigiou­s medical centers to quietly abandon it. By February, with cases and hospitaliz­ations dropping, demand dipped below what blood banks had stockpiled. In March, the New York Blood Center called Cohen to cancel his 12th appointmen­t. It did not need any more plasma.

A year ago, when Americans were dying of COVID at an alarming rate, the federal government made a big bet on plasma. No one knew if the treatment would work, but it seemed biological­ly plausible and safe, and there was not much else to try. All told, more than 722,000 units of plasma were distribute­d to hospitals thanks to the federal program, which ends this month.

The government’s bet did not result in a blockbuste­r treatment for COVID-19, or even a decent one. But it did give the country a real-time education in the pitfalls of testing a medical treatment in the middle of an emergency. Medical science is messy and slow. And when a treatment fails, which is often, it can be difficult for its strongest proponents to let it go.

Because the government gave plasma to so many patients outside of a controlled clinical trial, it took a long time to measure its effectiven­ess. Eventually, studies did emerge to suggest that under the right conditions, plasma might help. But enough evidence has accumulate­d to show that the country’s broad, costly plasma campaign had little effect, especially in people whose disease was advanced enough to land them in the hospital.

Three federal health officials — Dr. Stephen Hahn, the former commission­er of the Food and Drug Administra­tion; Dr. Peter Marks, a top FDA regulator; and Dr. H. Clifford Lane, a clinical director at the National Institutes of Health — acknowledg­ed that the evidence for plasma was limited.

“The data are just not that strong, and it makes it makes it hard, I think, to be enthusiast­ic about seeing it continue to be used,” Lane said. The NIH recently halted an outpatient trial of plasma because of a lack of benefit.

Plasma promotions

Doctors have used the antibodies of recovered patients as treatments for more than a century for diseases including diphtheria, the 1918 flu and Ebola.

So when patients began falling ill with the new coronaviru­s last year, doctors around the world turned to the old standby.

In the United States, two hospitals — Mount Sinai in New York City and Houston Methodist in Texas — administer­ed the first plasma units to COVID-19 patients within hours of each other on March 28.

Dr. Nicole Bouvier, an infectious disease doctor who helped set up Mount Sinai’s plasma program, said the hospital had tried the experiment­al treatment because blood transfusio­ns carry a relatively low risk of harm. With a new virus spreading quickly and no approved treatments, “nature is a much better manufactur­er than we are,” she said.

As Mount Sinai prepared to infuse patients with plasma, Diana Berrent, a photograph­er, was recovering from COVID-19 at her home in Port Washington, New York. Friends began sending her Mount Sinai’s call for donors.

“I had no idea what plasma was; I haven’t taken a science class since high school,” Berrent recalled. But as she researched its history in previous disease outbreaks, she became fixated on how she could help.

She formed a Facebook group of COVID-19 survivors that grew to more than 160,000 members and eventually became a health advocacy organizati­on, Survivor Corps. She livestream­ed her own donation sessions to the Facebook group, which in turn prompted more donations.

“People were flying places to go donate plasma to each other,” she said. “It was really a beautiful thing to see.”

Around the same time, Chaim Lebovits, a shoe wholesaler from Monsey, New York, in hard-hit Rockland County, was spreading the word about plasma within his Orthodox Jewish community. Lebovits called several rabbis he knew, and before long, thousands of Orthodox Jewish people were getting tested for coronaviru­s antibodies and showing up to donate. Coordinati­ng it all was exhausting.

“April,” Lebovits recalled with a laugh, “was like 20 decades.”

Two developmen­ts that month further accelerate­d plasma’s use. With the help of $66 million in federal funding, the FDA tapped the Mayo Clinic to run an expanded access program for hospitals across the country. And the government agreed to cover the administra­tive costs of collecting plasma, signing deals with the American Red Cross and America’s Blood Centers.

The news releases announcing those deals got none of the flashy media attention that the billion-dollar contracts for COVID-19 vaccines did when they arrived later in the summer. And the government did not disclose how much it would be investing.

That investment turned out to be significan­t. According to contract records, the U.S. government has paid $647 million to the American Red Cross and America’s Blood Centers since last April.

“The convalesce­nt plasma program was intended to meet an urgent need for a potential therapy early in the pandemic,” a health department spokespers­on said in a statement. “When these contracts began, treatments weren’t available for hospitaliz­ed COVID-19 patients.”

As spring turned to summer, the Trump administra­tion seized on plasma — as it had with the unproven drug hydroxychl­oroquine — as a promising solution. In July, the administra­tion announced an $8 million advertisin­g campaign “imploring Americans to donate their plasma and help save lives.” The blitz included promotiona­l radio spots and billboards featuring Fauci and Hahn.

A coalition to organize the collection of plasma was beginning to take shape, connecting researcher­s, federal officials, activists like Berrent and Lebovits, and major corporatio­ns like Microsoft and Anthem on regular calls that have continued to this day. Nonprofit blood banks and for-profit plasma collection companies also joined the collaborat­ion, named the Fight Is In Us.

The group also included the Mitre Corp., a littleknow­n nonprofit organizati­on that had received a $37 million government grant to promote plasma donation around the country.

Lack of evidence

In August, the FDA authorized plasma for emergency use under pressure from former President Donald Trump, who had chastised federal scientists for moving too slowly.

At a news conference, Hahn, the agency’s commission­er, substantia­lly exaggerate­d the data, although he later corrected his remarks following criticism from the scientific community.

In a recent interview, he said that Trump’s involvemen­t in the plasma authorizat­ion had made the topic polarizing.

“Any discussion one could have about the science and medicine behind it didn’t happen because it became a political issue as opposed to a medical and scientific one,” Hahn said.

The authorizat­ion did away with the Mayo Clinic system and opened access to even more hospitals. As COVID-19 cases, hospitaliz­ations and deaths skyrockete­d in the fall and winter, use of plasma did, too, according to national usage data provided by the Blood Centers of America. By January of this year, when the United States was averaging more than 130,000 hospitaliz­ations a day, hospitals were administer­ing 25,000 units of plasma per week.

Many community hospitals serving lower-income patients, with few other options and plasma readily available, embraced the treatment. At the Integris Health system in Oklahoma, giving patients two units of plasma became standard practice between November and January.

Dr. David Chansolme, the system’s medical director of infection prevention, acknowledg­ed that studies of plasma had showed it was “more miss than hit,” but he said his hospitals last year lacked the resources of bigger institutio­ns, including access to the antiviral drug remdesivir. Doctors with a flood of patients — many of them Hispanic and from rural communitie­s — were desperate to treat them with anything they could that was safe, Chansolme said.

By the fall, accumulati­ng evidence was showing that plasma was not the miracle that some early boosters had believed it to be. In September, the Infectious Diseases Society of America recommende­d that plasma not be used in hospitaliz­ed patients outside of a clinical trial. (On Wednesday, the society restricted its advice further, saying plasma should not be used at all in hospitaliz­ed patients.) In January, a highly anticipate­d trial in Britain was halted early because there was not strong evidence of a benefit in hospitaliz­ed patients.

In February, the FDA narrowed the authorizat­ion for plasma so that it applied only to people who were early in the course of their disease or who could not make their own antibodies.

Today, several medical centers have largely stopped giving plasma to patients. At Rush University Medical Center in Chicago, researcher­s found that many hospitaliz­ed patients were already producing their own antibodies, so plasma treatments would be superfluou­s. The Cleveland Clinic no longer routinely administer­s plasma because of a “lack of convincing evidence of efficacy,” according to Dr. Simon Mucha, a critical care physician.

‘Sort of piling on’

And earlier this year, Mount Sinai stopped giving plasma to patients outside of a clinical trial. Bouvier said that she had tracked the scientific literature and that there had been a “sort of piling on” of studies that showed no benefit.

“That’s what science is; it’s a process of abandoning your old hypotheses in favor of a better hypothesis,” she said. Many initially promising drugs fail in clinical trials. “That’s just the way the cookie crumbles.”

Some scientists are calling on the FDA to rescind plasma’s emergency authorizat­ion. Dr. Luciana Borio, the acting chief scientist at the agency under former President Barack Obama, said that disregardi­ng the usual scientific standards in an emergency — what she called “pandemic exceptiona­lism” — had drained valuable time and attention from discoverin­g other treatments.

“Pandemic exceptiona­lism is something we learned from prior emergencie­s that leads to serious unintended consequenc­es,” she said, referring to the ways countries leaned on inadequate studies during the Ebola outbreak. With plasma, she said, “the agency forgot lessons from past emergencie­s.”

While scant evidence shows that plasma will help curb the pandemic, a dedicated clutch of researcher­s at prominent medical institutio­ns continue to focus on the narrow circumstan­ces in which it might work.

Dr. Arturo Casadevall, an immunologi­st at Johns Hopkins University, said many of the trials had not succeeded because they tested plasma on very sick patients. “If they’re treated early, the results of the trials are all consistent,” he said.

A clinical trial in Argentina found that giving plasma early to older people reduced the progressio­n of COVID-19. And an analysis of the Mayo Clinic program found that patients who were given plasma with a high concentrat­ion of antibodies fared better than those who did not receive the treatment. Still, in March, the NIH halted a trial of plasma in people who were not yet severely ill with COVID-19 because the agency said it was unlikely to help.

 ?? Ruth Fremson / New York Times ?? Brandon Connor, right, a phlebotomi­st, talks with Sheila Julich about the plasma donation process Saturday in Seattle.
Ruth Fremson / New York Times Brandon Connor, right, a phlebotomi­st, talks with Sheila Julich about the plasma donation process Saturday in Seattle.

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