John P. Moore, PhD, has studied antiviral antibodies and how vaccines can trigger their production for more than 30 years. He is a professor of microbiology and immunology at Weill Cornell Medicine in New York City. Melissa Cushing, MD, is the medical director of transfusion medicine and vice chair of laboratory medicine at New York-Presbyterian Hospital, Weill Cornell Campus. She is the principal investigator for the New York Coordinating Center of CONCOR-1, one of the largest Covid-19 convalescent plasma randomized clinical trials in the world. The opinions expressed in this commentary are the authors'. View more opinion on CNN.
(CNN)The Food and Drug Administration's shocking decision this week to allow the use of Covid-19 convalescent plasma to treat sick patients was by all appearances motivated by a desire to appease President Donald Trump rather than on any serious consideration of the science.
FDA Commissioner Stephen Hahn left the medical community aghast when he said, at a news conference on Sunday, that 35 of 100 people sick with Covid-19 "would have been saved because of the administration of plasma."
Researchers and doctors were confused by Hahn's comments. We were, even after combing through the preliminary manuscripts from the Mayo Clinic on the efficacy of using plasma from Covid-19 patients, from which this claim was reportedly drawn.
The manuscripts, by the way, have not been peer-reviewed and do not describe a randomized clinical trial that proves Covid-19 convalescent plasma, or CCP, is effective. One of them presents pooled data drawn from CCP studies in multiple countries including China, Iran, Iraq and Mexico. In short, we need much more information than we now have.
Hahn later walked back his comment about how many lives are saved by CCP (he said on Twitter that criticism of his remarks was "entirely justified") but there's still considerable confusion in the medical world that needs clearing up as it further complicates communications between physicians and their patients.
The FDA's decision has real consequences for understanding how CCP should be used to treat the disease, and when it will most likely not be useful. Normally, such questions would be resolved by randomized clinical trials, but completing such trials may now be difficult or even impossible.
With CCP now generally available under an Emergency Use Authorization, will patients still volunteer to join a randomized trial, knowing that they might actually receive a placebo? Will physicians refer their patients to a randomized trial, or simply go ahead and use convalescent plasma anyway? CCP is already in short supply, so will there be enough to meet increased demands?
All the more reason, then, to understand the strengths and weaknesses of CCP therapy. If it turns out to be impossible to prove that CCP therapy is effective via randomized clinical trials, all we can do is apply common sense and the limited data already available in the scientific literature and via academic networks. This is far from ideal, but may now be the scenario we face, unfortunately.
The scientific basis of CCP therapy is giving an outside boost to a patient battling the virus. The plasma contains virus-neutralizing antibodies -- proteins that recognize the invading virus, bind to it at specific locations and prevent it from infecting human cells. They "neutralize" the virus.
CCP therapy is very soundly based on decades of experience with other infections. It's generally considered quite safe, but all blood products carry some risk, including rare but fatal transfusion reactions and transfusion-transmitted infections. Safety assessments in large randomized clinical trials are important for good reasons!
But CCP therapy can only work well when the patient receives enough antibodies to make a difference. And all too often that's simply not the case.
The amount of antibodies in the blood of Covid-19 patients depends on the severity of the infection and when the measurement is made. The sickest patients have the most antibodies, even those who go on to die. People with mild symptoms who recover at home usually have only very low levels of these antibodies.
The best donors are seriously ill hospital patients who recover, are discharged and then give their plasma within the next month or two. Plasma donations from people who recover from mild infections are all too often not useful. Because this point is not widely understood by the general public and perhaps not even by all physicians, it can lead to a significant waste of resources.
The FDA has recommended using only CCP with a minimum strength of antibodies, although physicians are allowed to use any CCP they can get their hands on. Experience in our and colleagues' laboratories tells us that nearly half the plasma samples from prospective CCP donors don't reach the FDA's standard, while others only barely make it.
This suggests that much of the significant effort of screening donors and collecting CCP is wasted, and if the screening is not done, then patients have a good chance of receiving a useless infusion.
Another key point is that hospitalized Covid-19 patients rapidly produce virus-neutralizing antibodies in their own plasma -- so much, in fact, that adding donor plasma to the mix often leads to only a negligible increase in useful antibodies .
CCP therapy is not a simple procedure. Considerable efforts are being made to obtain suitable plasma units and then use them. It's not helpful, and indeed very wasteful and potentially harmful, if the wrong CCP units are used at the wrong time in the wrong patients. There's enough knowledge already around, including preliminary information from randomized clinical trials, and the hints in the Mayo Clinic manuscripts, to know that it's best "to hit early, hit hard".
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But to use CCP therapy effectively, only the most antibody-rich plasma should be used. And it should be given early, within the first week after the patient enters hospital, preferably the first three days. If CCP infusions are delayed much longer than a week, the amount of extra antibodies provided will probably be the proverbial drop in the bucket.
But again, only randomized control trials will tell us the real answers--and the safest and actually effective way to use CCP therapy for Covid patients.
President Trump was never going to tell the public that. But the FDA should have—and now it must.
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