Blood plasma looked like a promising covid-19 treatment. Then Trump got involved.

But when President Trump politicized and overhyped his administration’s authorization last month of convalescent plasma to treat covid-19, he spawned confusion about the treatment and triggered a political backlash that specialists say has stifled an expected spike in demand.

Now leaders of the effort to expand use of convalescent plasma are scrambling to reassure the public that the treatment does have merit, while fending off unfavorable comparisons to Trump’s previous pet coronavirus treatment, hydroxychloroquine. Under similar pressure from Trump, the Food and Drug Administration authorized emergency use of hydroxychloroquine early in the pandemic only to withdraw the order in June when rigorous clinical trials proved the drug was ineffective.

Doctors and proponents of convalescent plasma treatment say the comparisons to hydroxychloroquine are both unfair and inappropriate. They say plasma with high levels of coronavirus-fighting antibodies holds promise and is safe, unlike hydroxychloroquine, which poses a risk of fatal cardiac events.

“It’s a real shame that it has gotten politicized the way it has. The comparisons to hydroxychloroquine are unjustified because they are very different products and the safety data is very different,” said Kate Fry, chief executive of America’s Blood Centers, a coalition of nonprofit blood donor banks that has the largest government contract to gather plasma from recovered coronavirus patients.

Advocates are attempting to keep on track randomized clinical trials that should prove definitively whether the treatment carries benefit, although making the drug more widely available has made it harder to recruit trial subjects who might receive a placebo.

“We know there needs to be more randomized clinical trials and we need that for further efficacy data,” Fry said. “In the meantime, this is something that can help people, and we are making sure they have access to it.”

Physicians also have expressed frustration with the highly charged atmosphere that has engulfed the research, in which they say people make medical decisions based on their feelings about Trump and his handling of the pandemic.

“There’s been a level of confusion that has been injected into it and a level of emotional response,” said Shmuel Shoham, an infectious-disease clinician and researcher at Johns Hopkins University School of Medicine who is leading clinical trials of plasma. “People have different ideas what the data means that have nothing to do with data, because of allegiances to tribes.”

Convalescent plasma has been used for more than a century to treat people stricken with infectious diseases. People who have already recovered from the virus build up antibodies in their blood plasma that can be beneficial to people who still have the illness. The Trump administration identified plasma as a potential therapy early in the pandemic, and the FDA selected Mayo Clinic to make it available on a compassionate-use basis across the country, called an “expanded access program,” that was closely coordinated with the agency.

In the days before the FDA issued its emergency use authorization, Trump accused the agency in a media briefing of dragging its feet on convalescent plasma, and on Twitter he blamed the “deep state” for slowing down drug and vaccine approvals. Then, on Aug. 23, the eve of his Republican nominating convention, Trump unveiled the FDA authorization for plasma. Although it was based on inconclusive patient data from Mayo’s program, not a randomized clinical trial that would be a stronger test of its effectiveness, he declared convalescent plasma a major “breakthrough’” in the fight against coronavirus and said it “had an incredible rate of success.”

FDA Commissioner Stephen Hahn compounded the confusion and raised further questions about the FDA’s independence by exaggerating the benefits of the treatment at Trump’s press briefing, then backtracking the next day.

The absence of a jump in transfusions since the emergency use authorization reflects public and physician uncertainty over the administration’s shifting response, as well as a lack of sound data about which patients might benefit the most, they said.

“Surprisingly, we haven’t seen a spike in demand,” said Pampee Young, chief medical officer of the American Red Cross. “I think it could be in part some of the negative press that came out.”

The government-sponsored drive to collect hundreds of thousands of units of plasma from coronavirus survivors is called the Fight Is in Us. Using celebrities to help deliver the message — including Helen Mirren and Johnson, who recorded videos using the campaign’s catchphrase that donors “can literally save lives” — the drive has persuaded tens of thousands of recovered coronavirus patients to contribute their plasma so it could be transfused into someone else fighting the disease.

It is led by Microsoft, Mayo, the American Red Cross and other nonprofit blood banks, as well as for-profit plasma collection centers that are gathering plasma to produce another, potentially better treatment from concentrated plasma called immune globulin. The Bill and Melinda Gates Foundation also participated in the effort. The Fight Is in Us website uses a “plasmabot” program to provide potential donors with a list of collection centers nearest to them.

Mayo Clinic has received $49 million from the government to run the plasma program, according to public records. America’s Blood Centers has received $201 million and the American Red Cross has received $69 million. Mitre, a federally funded research and development center based in Massachusetts that is also leading the initiative, has received more than $20 million. Microsoft, which provided leadership of the donor drive, said its participation was philanthropic and it was not paid.

Department of Health and Human Services officials, including Hahn and Anthony S. Fauci, were part of a parallel, $8 million public relations initiative appearing in TV, radio and billboard advertising. Each of those officials used variations of the catchphrase that coronavirus survivors “can literally save lives.”

“The Fight Is In Us coalition came together because we collectively believe that the antibodies of covid-19 survivors can play a critical role in turning the tide against this pandemic,” Peter Lee, Microsoft’s corporate vice president for research and incubation, in an emailed statement.

“We’re committed to evidence-based decision-making, and building trust with donors, doctors, and potential recipients,” Lee said. “We’re eagerly awaiting the results of randomized controlled trials for convalescent plasma and hyperimmune globulin, and in the meantime will continue to do our part to attract enough plasma donors to support these scientific efforts.”

The initiative led to treatment in more than 105,000 coronavirus patients and produced the data the FDA used to issue its Aug. 23 emergency use authorization for the treatment. The data showed that, among patients who were not intubated, 11 percent of those who received plasma with high levels of coronavirus antibodies died within seven days of transfusion, compared with 14 percent of those who received plasma with low antibody levels.

FDA used that information to say plasma “may be effective,” the minimum threshold for an emergency use authorization. A National Institutes of Health clinical guidelines panel struck a more skeptical tone after the FDA’s action.

“There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of covid-19,” the panel said.

Mayo said its job for the government was to make convalescent plasma available through a compassionate use program and to test its safety. That evolved into an analysis of efficacy, it said.

“The FDA has asked for additional data for review by their teams, and Mayo Clinic is providing those data. The discussion and simultaneous analyses continue,” Mayo spokesman Robert J. Nellis said in an email. “We’re confident in the data we’ve provided to the FDA and the scientific community and look forward to continuing to contribute to a medical solution to this pandemic.”

Arthur Caplan, a medical ethics specialist at New York University’s Langone Medical Center who has closely studied compassionate use of unapproved treatments, said the government and Mayo clinic should have launched a controlled clinical trial to determine whether the treatment worked better than a placebo or some other treatment. Without that, the question marks loom large, he said.

Mayo’s expanded access effort started as “panic prescribing,” he said. Then Hahn’s misstatement that the treatment improved coronavirus survival by 35 percent fueled the political fires, Caplan said.

“There’s an increasing worrying concern on the part of the public that things are getting rushed and overly hyped,” he said. “Some people say, ‘I trust the president, and it’s good,’ and other people say, ‘If he says it works, I’m not touching it.’ “

Still, plasma treatment has been supported by many physicians and scientists in the mainstream, while hydroxychloroquine gained traction largely through the promotion by Fox News commentators and Internet posts by little-known doctors.

Trump meanwhile has also made repeated promises that a vaccine will be made available before Election Day, even though top officials overseeing vaccine development say that is highly unlikely. Amid Trump’s bid to rush a vaccine, drug company CEOs responded with an extraordinary joint pledge to not seek approval before safety and efficacy has been established in Phase 3 clinical trials.

A group called Survivor Corps has more than 100,000 followers on Facebook where plasma donors post selfies while they are hooked up with tubes to machines drawing their blood, straining off the yellow fluid, and putting the rest back in their bodies. Survivor Corps founder Diana Berrent, who has attracted corporate support to the cause, said donating plasma gave coronavirus survivors a strong sense of purpose during the pandemic lockdowns and social distancing.

“We were being told as a country, the best you can do is literally do nothing,” she said. “It goes against the human spirit, and we want to help.”

The political fights that have erupted over plasma anger Scott Cohen, a Long Island coronavirus patient who received an infusion of convalescent plasma, subsequently recovered, and has now begun donating his own antibody-rich plasma to help others. Cohen does not place all the blame on Trump.

“I find that politicizing any portion of this is so incredibly wrong,” Cohen said, “and it’s happening on both sides.”