The Trump administration gave convalescent blood plasma the emergency go-ahead as a treatment for Americans battling COVID-19, but infectious disease experts said they fear this step could sabotage clinical studies aimed at determining the effectiveness of the treatment.
U.S. Health and Human Services Secretary Alex Azar hailed the FDA's emergency authorization for the use of convalescent plasma as a "milestone" in the fight against the coronavirus pandemic.
But Dr. Thomas M. File Jr., president of the Infectious Diseases Society of America, said while the therapies have shown promise, especially if administered early, researchers need more data from randomized, double-blind studies _ those in which neither the subjects nor those conducting the study know which subjects are in the test and control groups.
When it comes to plasma therapy, scientists lack data from controlled trials needed to answer crucial questions: Does it work better than a placebo? How long does it work? Which groups of patients _ the severely ill or early stage patients _ derive a benefit from getting plasma? Where does it make a difference? Where does it change outcomes?
Convalescent plasma is not likely to hurt anybody, but no one knows conclusively that it will help anyone either, said Dr. Stuart Cohen, chief of UC Davis Health's Division of Infectious Diseases. By expanding access to the plasma treatment, he and other researchers said, fewer people could opt to roll the dice on a randomized trial where they might get the placebo rather than antibody therapy.
That troubles Gina Warren, a Sacramento resident who worked as a pharmacist for 20 years at Health Net and then the county of Sacramento. This move could leave those questions forever unanswered for marginalized people desperate for an effective treatment, she said.
"If the experts are saying it's not time yet, we need to listen," she said. "We need to listen because what we don't want is more harm because we implemented it or by fast-tracking it and having it used inappropriately and we see an increase in morbidity and mortality."
Blood plasma already being used in Sacramento
What Sacramento-area residents should know is medical groups in the region have been treating patients with convalescent blood plasma for several months now _ as early as April for Dignity Health and UC Davis Health.
They gained access through an expanded access program that the U.S. Food and Drug Administration approved at the Mayo Clinic, Cohen said.
The FDA's emergency approval means doctors will have to fill out less paperwork to get doses of the drug for individual patients, Cohen said. Rather, "this would be just like what's going on now with (the antiviral drug) remdesivir. If you have a patient whom you think meets the criteria, they could be treated."
Convalescent plasma has been in use for more than a century to counter different diseases, and it was used to treat patients during the 1918 influenza pandemic, said Dr. Parimal Bharucha, an intensive care doctor at Dignity's Mercy San Juan Medical Center in Carmichael.
The idea is that patients who had COVID-19 but fought it off have built up a storehouse of antibodies in their blood plasma, Bharucha said. Doctors can then take those antibodies from the recovered patient's blood and give them to sick patients to help them fight off the infection.
"The way it helps would be that the patient's body is making its own antibodies, but it takes time to make those antibodies. You are just giving those antibodies from the outside to help fight the infection of patients in their own immune system manufacturing more antibodies," Bharucha said in a recent interview. "What this means is when somebody gets infected, they fight the infection.
"At the molecular level, you can see antigens from the infection. To fight them, the body makes antibodies. The antibodies are like soldiers. They fight for us. They go out and attack the antigens."
Once the antibodies have fought off the antigens, the patient is infection-free, he said, but the antibodies are still circulating in the body.
Dr. Namrita Gogia, who is leading Dignity's COVID-19 convalescent plasma effort, said results from the Mayo Clinic's expanded access program have shown that the plasma treatment has been most beneficial in treating COVID-19 patients with severe symptoms, especially when used early.
After observing COVID-19 patients, she said, providers believe the plasma treatment is shortening their stays in Dignity hospitals, helping them to beat symptoms such as shortness of breath and reducing the need for help with oxygen levels.
Dignity uses a variety of methods to treat patients with COVID-19, Gogia said, and two of those _ remdesivir and the steroid dexamethasone _ have resulted from randomized, double-blind trials with control groups and hundreds of participants.
That's the rub for Cohen, File and others. More study, more trials and more concrete data is needed to solve the mystery and open the door to wider use.
Current evidence of the effectiveness of the treatment come from only two small randomized trials and they indicate patients treated with convalescent plasma are seeing improved outcomes a little more than a third of the time.
"The only way that we will ever move anything forward is to do studies that really demonstrate that there's benefit," Cohen said. "If we're ever going to think of this as a long-term strategy, then I think we have to understand that the only way to prove anything is ever going to be of any benefit is to do a randomized trial where somebody gets plasma and somebody doesn't, and they're matched groups."
Warren echoed that sentiment: "We're all desperate to get a vaccine. We're desperate to get treatments, but what we want to make sure is that it's not politicized and we're not doing it for monetary reasons but to actually slow down the morbidity and mortality of this virus and the impact that it has had on Black and brown communities."
Warren's concerns, however, do not end at the still-unclear science and the perils of rushing out a remedy before it is ready.
She also sees the potential implications for skeptical groups hit disproportionately hard by the virus and by racial biases in accessing and receiving health care.
That mistrust runs especially deep in the Black community where memories of the infamous Tuskegee Experiments _ during which doctors from the U.S. Public Health Service injected healthy Black men with syphilis between 1932 and 1972 to track the effects of the disease if left untreated.
The men who participated in the study weren't told of what was being introduced into their bodies, but did so with the promise of free health care.
The experiments ruined hundreds of lives before the program was finally shut down and continues to cast long shadows over Black America, deeply damaging trust in the health care industry and its officials, Warren said.
"We already have challenges because there's a lack of trust in the health care industry, especially with the Tuskegee Experiments," said Warren, who is Black. "What my concern is for our community is that we will be the ones that they're testing on. When you don't have enough information, you have to have controlled trials. If there's not enough clinical trials, you have to have controls.
"You go to the most marginalized, most vulnerable populations because, a lot of the time, those patients don't have options, and providers are telling them this is an option. They just may not understand that there's a lot of questions that still need to be answered."
That long standing skepticism is well-deserved, Cohen said.
"There are a lot of barriers to getting African Americans in particular to participate in clinical trials. Even though we're all too young for this, those Tuskegee Experiments are still in people's minds, as to what was done, and so everyone is a little bit worried about being a guinea pig and whether people are being as unethical as they were in the past. So I get it," Cohen said. "What I would just say is that this is how you move things forward."
Cohen sees some parallels in the battle against COVID-19 as those he faced as he and other investigators tried to come up with treatments that would end the AIDS epidemic. Once patients and people in the community became more involved in the planning of drug trials, attitudes began to change.
"I think that's something that probably would make people a lot more comfortable, if members of their community were at the very least on community oversight committees that would look and see how these experiments are designed," he said. "So people are involved and you've got advocates."
