Convalescent plasma isn’t quite the coronavirus miracle treatment it was supposed to be. What happened?

Back in the spring, the pleas for donated plasma from coronavirus survivors were desperate. Doctors hoped then that the antibodies from survivors’ blood could save the sickest patients from succumbing to the virus. 

Now, 10 months into the pandemic, there is no evidence that convalescent plasma — the liquid part of blood collected from patients who have recovered from an infection — prevents hospitalized COVID-19 patients from getting worse. 

The blood bank at Children’s Hospital Colorado, the first in the state to begin taking convalescent plasma in late March, has suspended its collection. And Denver Health decided after a December review of nationwide data that the hospital will no longer transfuse its patients with the plasma to treat the coronavirus.

It was the miracle treatment that didn’t materialize.

Demand for convalescent plasma is low in Colorado, in part because of declining cases of coronavirus, but also because of its lackluster performance in a handful of research studies across the globe that focused on hospitalized patients. Several blood banks are still collecting it, but much of the plasma is shipped to other states where cases are spiking and doctors are still turning to it to help hospitalized patients.

“The hope was that it would help patients recover faster … it would help them get better faster or prevent their disease from progressing,” said Dr. Tim Jenkins, an infectious disease doctor at Denver Health whose job is to evaluate potential therapies for COVID-19 patients. “None of these recent studies have shown that.” 

None of the nearly 40 patients who have received convalescent plasma at Denver Health since April had a dramatic turnaround because of it, Jenkins said. And no real benefits were found in an observational study of hospitalized patients who were given convalescent plasma at Denver Health and UCHealth University of Colorado Hospital in Aurora beginning last spring.

Similarly, a study published in the New England Journal of Medicine in November found “no significant differences” in mortality rates between more than 200 patients in Argentina who were given either convalescent plasma or a placebo. 

Still, a handful of large-scale studies are ongoing and researchers are trying to pinpoint whether the plasma helps a specific subset of patients — most likely patients who are at the beginning of their illness and not already hospitalized. 

A study published this week, for example, found that older adults who received a plasma transfusion within three days of getting coronavirus symptoms were less likely to get as severely ill as those who did not. Half of the 160 patients involved in the study received plasma with a high concentration of coronavirus antibodies. 

Another national study in the works is looking at whether convalescent plasma will benefit patients who show up in emergency rooms. The study involves 50 emergency departments across the country, including University of Colorado Hospital in Aurora.  

Hospitals revise protocol on convalescent plasma

Denver Health physicians still could use the plasma in “extenuating circumstances” but will no longer use it routinely, Jenkins said. 

Any blood transfusion comes with risks, such as an allergic reaction, and there is no known benefit to using convalescent plasma on hospitalized coronavirus patients, he said. Instead, the hospital is finding success with two drugs that have become part of the protocol for coronavirus treatment as medical practices have evolved during the past 10 months — the antiviral remdesivir and the steroid dexamethasone. 

Convalescent plasma was cast as the hero in a few stories of dramatic recovery from COVID-19 in the early days of the pandemic, including that of Dr. Michael Leonard, an anesthesiologist from Evergreen who was the first patient in Colorado to receive the treatment. After his family pleaded in the media for a plasma donor, Leonard received a transfusion and, after 34 days on a ventilator, recovered from the virus. 

“There are certainly anecdotal reports out there” about surprise recoveries, Jenkins said. “It’s also possible that it was simply timing. Most people recover from COVID-19 anyway.”

At University Hospital, doctors are advised to use convalescent plasma only as part of two clinical trials the hospital has joined. The national trials focus on patients not yet admitted to the hospital or within three days of admission. 

Still, patients hospitalized with the coronavirus are sometimes “very passionate” about receiving the plasma because they’ve heard about it in the news, said Dr. David Beckham, a University physician and researcher who is studying the neurological effects of COVID-19.  

He understands why people insist on plasma, even after their physician has explained there are better outcomes with two other treatments, remdesivir and dexamethasone. 

“The standard of practice rapidly changed based on just how quickly we were able to perform these studies and learn,” Beckham said. “That’s confusing for people, because early on they get one message that this is how we are approaching it and now, six, eight months later, we have this different message.” 

Beckham is hopeful that ongoing studies will find convalescent plasma helps some portion of COVID-19 patients, noting that evidence so far points toward highly concentrated transfusions that happen early on. Just like the plasma taken from coronavirus survivors, lab-engineered antibodies — called monoclonal antibodies — seem to work best in highly concentrated doses, soon after the onset of symptoms, according to the first research studies. 

“In sick, hospitalized patients, those antibodies don’t work either,” he said. “But they do actually seem to work and improve outcomes in patients that are very early in their course of disease.”

Vaccine adds layer of complication to plasma collection

The blood bank at Children’s Hospital in Aurora made national news when it became just the third site in the nation to collect convalescent plasma that was transfused into a COVID-19 patient. 

Then in late August, after the FDA released guidelines for use of convalescent plasma that required the bank to switch to a new antibody test, it paused operations. The blood bank hasn’t started up again, and has no plans to do so, because requests for the plasma in Colorado have slumped, said Dr. Kyle Annen, medical director of transfusion services and patient blood management at Children’s.

When she hit pause, the bank had 50 units of plasma stockpiled. 

And by then, Annen and her team were learning that it was difficult to find patients with a high enough concentration of antibodies in their plasma to meet the threshold most likely to help a sick patient. 

A study by the Children’s blood bank, coming out in April in the medical journal Transfusion, will say that only about 20% of coronavirus survivors who donated plasma at Children’s had a high enough concentration of antibodies to make the cut as “high titer,” Annen said. 

The antibody levels in survivors’ blood waned so quickly that by the time the bank got the patients in to give plasma, it was often too late, Annen said. The window was short; most people’s antibodies were in high enough concentration for only a couple of weeks. “The antibody levels from people who have recovered from COVID are kind of all over the place,” she said.

And now another factor — the coronavirus vaccine — will add to the complication of collecting convalescent plasma. 

The FDA requires that people who donate convalescent plasma have antibodies because they had a COVID-19 infection, not because they received a vaccination. Sorting that out adds another hitch in finding donors, Annen said. 

Colorado is sharing plasma with California, mountain region

But other blood banks in Colorado are still collecting convalescent plasma, including Vitalant, a nationwide nonprofit with nine collection sites in Colorado and mobile blood banks that stop around the state. 

For now, the blood bank is sending much of the plasma collected in Colorado to other states where coronavirus cases are spiking or where there are more hospitals asking for the plasma. 

While the national research on hospitalized patients so far has been discouraging, Vitalant’s director for research and scientific programs, Larry Dumont, said he still hears of so-called “Lazarus patients” who have a dramatic recovery after receiving a transfusion. “They were really bad and they gave them a transfusion and they walked out of the hospital in two days,” he said, acknowledging that “that’s not scientific proof.” 

Whether to use it on COVID-19 patients varies widely across hospitals and among physicians across the country, Dumont said. Nationally, Vitalant last week had its highest level of collections so far since the pandemic began, responding to calls from the federal Biomedical Advanced Research and Development Authority this summer to build up a national stockpile. 

Vitalant’s mountain division, which includes Colorado, North Dakota, South Dakota, Wyoming and Montana, has made 3,820 collections since April, producing 14,000 units for patient use. The nonprofit can track where the COVID-19 hotspots are by the percentage of people who have antibodies when they donate blood. 

“There are a number of people that are healthy and walking around and they come in to donate blood and have the antibodies,” he said. In Colorado, 9.7% of donors have antibodies. In North Dakota, it’s 21%, he said. 

In some parts of the country, including the Midwest, blood banks are unable to keep up with hospital requests for convalescent plasma, Dumont said. “If you go to Los Angeles right now, it’s crazy, of course,” he said. 

At the blood bank at St. Mary’s Medical Center in Grand Junction, collection has slowed based on demand, said director Jennifer Rhamy. The bank, which supplies fellow SCL Health hospitals in Colorado plus more than a dozen other hospitals in western Colorado and eastern Utah, is filling orders for 20-30 units of convalescent plasma per month. 

This week, the hospital shipped 20 units to a hospital system in Los Angeles, where hospitals have reached capacity for coronavirus patients. 

Most of the plasma is low concentration, or “low titer,” Rhamy said, which means a patient would require more doses than if they were getting plasma with a high concentration of antibodies. “We are not seeing as many high-titer donors as we would like,” she said. 

The greater concern, though, is low blood supply in general, as the pandemic has cut down on the center’s ability to hold blood drives at local workplaces. 

“That keeps me up at night much more than trying to keep up with the convalescent plasma,” Rhamy said. “We’re critical. We’ve got to get more blood donations in.”