When COVID-19 spread around the world in the spring, only one experimental therapy seemed like a sure bet: blood plasma from people who had recovered from the disease.

After all, convalescent plasma had been used for a century to battle other infections, recovered COVID-19 patients were eager to donate their blood, and the scientific rationale for the treatment was solid. Plasma contains the antibodies that the body produces to fight a new infection.

Instead, convalescent plasma has become yet another political and regulatory controversy, and the evidence that it helps COVID-19 patients is inconclusive and conflicting.

The latest letdown, a randomized trial of 464 moderately ill patients conducted in hospitals across India, was published last week in the journal BMJ. Even though patients who were given plasma cleared the virus more quickly than a comparison group, there was no difference in terms of progression to severe disease or death.

An editorial accompanying the study was bluntly titled, “Convalescent plasma is ineffective for COVID-19.”

That conclusion is premature, said Mohamed S. Alsammak, a clinical pathologist and director of transfusion medicine at Temple University Hospital.

Alsammak led Temple’s participation in a study that gave plasma to tens of thousands of hospitalized COVID-19 patients across the country. The results, published in August, suggested plasma modestly reduced deaths, but only if it contained high levels of antibodies and was used early in the infection. The study, overseen by the Mayo Clinic, was limited by not having a comparison group that did not get plasma.

Why is earlier better than later? Alsammak explained that as COVID-19 progresses and becomes severe, it often triggers abnormal immune responses, including damaging inflammation and proteins that attack healthy cells. At that point, he said, neutralizing the virus with antibodies will not reverse or stop the disease.

» READ MORE: COVID-19 patients can be overwhelmed with inflammation. Doctors are learning to calm that ‘storm.’

“I still don’t think this [latest study] is conclusive,” Alsammak said on Thursday. “By the time the patients presented to the hospitals, they had moderate to severe symptoms.”

That sentiment was echoed by John Zurlo, chief of infectious disease and chair of the COVID-19 clinical task force at Jefferson University Hospital, where plasma is one of numerous treatments being studied.

“Our best data at this moment suggests that if plasma is going to work, it needs to be given very early in the course of infection, before they develop serious dysfunction," Zurlo said.

The dilemma, he acknowledged, is that most patients don’t go to the hospital until they are really sick.

More than 150 clinical studies of convalescent plasma for COVID-19 are continuing around the world, according to clinicaltrials.gov, the U.S. government’s catalog of human research studies. Among these is a randomized trial at the University of Pennsylvania designed to see if plasma helps pneumonia due to COVID-19.

Even so, enthusiasm for the therapy may have waned, partly because of controversy surrounding it. In August, top government scientists, including White House coronavirus advisor Anthony Fauci, reportedly urged the U.S. Food and Drug Administration to hold off giving emergency authorization to plasma because the evidence was still too weak. But President Trump, eager to claim progress against the pandemic, announced on Aug 23 that the FDA was authorizing what he called "a powerful therapy” made possible “by marshaling the full power of the federal government.”

“We transfuse less than before,” said Alsammak at Temple. “Clinicians are very selective.”