Since the first patients began to recover from COVID-19, there have been tests in the use of blood plasma from those recovering patients as a means of treating those still fighting through the disease. However, even as some classes of steroids, anti-viral drugs, and simple procedural changes have demonstrated effectiveness in reducing the severity of COVID-19 in hospitalized patients, there has been relatively little news about convalescent plasma. Despite this, the practice has become widespread and multiple studies around the globe have enrolled tens of thousands of patients.
Now the first results from the largest study in the United States have become available, and they’re decidedly … confusing. Even though the study seems to suggest that there was some benefit from administering plasma to patients already positive for COVID-19, the data from the tests is so confusing that even statistical experts are having trouble digging out information of value. Health officials, including Dr. Anthony Fauci, are calling the data “weak” and suggesting that the FDA put any emergency approval for convalescent plasma on hold.
The use of convalescent plasma has been supported by Donald Trump, but unlike the other hearsay and nonsense remedies that Trump has supported, there’s some sound science behind the use of plasma. It’s been used both for treatment and providing temporary immunity in several diseases, including proving valuable in the fight against Ebola. Multiple papers have suggested exactly this form of “passive immunization” as a means of fighting emerging diseases in advance of any available vaccine.
Despite widespread use of convalescent plasma in fighting COVID-19, there have not been the kind of published, peer-reviewed results that support the idea that it can play a significant role, particularly as a treatment of patients who are already ill. And what’s particularly frustrating is that it may well turn out that plasma from recovered patients is extremely helpful; it’s just that this trial, conducted by the Mayo Clinic, was not.
The pre-print of the study results shows what appears to be a statistically significant improvement in mortality rates for patients with severe COVID-19 who received plasma early in their treatment. But it’s the ability to compare how these patients fared against patients who did not receive plasma that’s really concerning—because there’s no control group. Researchers involved seemed to have continuously expanded the rolls of those drafted into receiving plasma until they covered all patients, with no one receiving a placebo and no group of patients treated as controls for the study.
It’s an understandable response in a situation where doctors are frustrated by the lack of effective treatments and dealing with a disease where mortality is very high, but it means that coming out of the study it’s very hard to claim a better understanding than going in. And the result appears to be that, despite the claim of improved outcomes, the FDA will not move ahead with an Emergency Use Authorization (EUA) that could make convalescent plasma more widely available.
As The New York Times reports, the hold on moving forward is supported by a number of health officials, including Fauci. Without the control group, all the study really provides is a difference in survival rates between those who got plasma early (8.7% mortality) and late (11.9% mortality). This difference is just broad enough to be statistically significant, but it doesn’t really show a difference versus patients who didn’t receive plasma, or compare plasma against what has become an increasingly effective standard of care. Even during the period of the study, survival rates have risen significantly, in part because of the use of steroids for intubated patients, in part because of increased use of high oxygen treatment over intubation, and in part because of a number of changes made to how patients with severe COVID-19 are treated. These changes make it even more difficult to pull out the effect of plasma without an effective control group.
Even though the EUA has been placed on hold pending a better look at available data, it appears that the “expanded access program” at sites already enrolled in the study of convalescent plasma will continue.
