The use of “convalescent plasma”—blood plasma from people who have recovered from an infectious disease—has been a common treatment going back for decades. From ZIKA and flu, to Ebola and SARS, direct administrations of the antibodies contained in the blood of disease survivors has been trialed as a potential means of conferring at least some immunity on others. For some diseases it works remarkably well, for others the effect of plasma therapy is less potent, but the trials are an obvious step toward finding a means of fighting a disease when neither conventional treatment nor vaccines are available.
Widespread trials of convalescent plasma are currently underway with COVID-19 patients, and early results of those trials have been hopeful. The primary focus of these trials has been, understandably, on the hope that plasma therapy might provide a tool to help those seriously ill when other treatments had been unsuccessful. But there’s another potential use of the antibodies provided by survivors—a prophylactic use. These antibodies might provide a temporary immunity to COVID-19 for those who have not yet been infected. It wouldn’t be a vaccine, because the protective effect would likely fade in a matter of weeks, but it might provide a safety net for those on the front line of fighting the disease and those most vulnerable, until a vaccine or better treatments are available. So … why isn’t this happening?
The University of California San Diego is about to launch a trial of exactly this ability to use plasma therapy as a means of transferring “temporary immunity.” The university is seeking donors who have tested positive for COVID-19, and have recovered from illness. Their plasma will be used in a trial targeted at reaching 487 participants, where the participants have a high risk factor ”such as age or an underlying condition” or are in a position, such as healthcare workers, where they’re are known to face probable exposure.
The UCSD study is part of a series of studies coordinated through Johns Hopkins looking at plasma as both a treatment and a preventative. Those trials began back in April, and recruitment for the first prophylactic trial began in May. Early results have indicated that plasma appears to be safe for patients, and with over 7,000 patients enrolled in therapy trials, the outcomes there appear to indicate that plasma treatment is helpful, though far from a silver bullet.
There do not appear to be any published results from prophylactic trials at this point—which is not surprising. As with vaccines, trials of any prophylactic tend to be time-consuming affairs that are based more on statistics than direct evidence. It’s easy to see failure: If a large number of those enrolled catch the disease, then the trial is unsuccessful. But if participants in the trial don’t come down with COVID-19, or the disease affects only a few participants; is that because the prophylactic is successful, or because the patients weren’t exposed? The ethics of deliberately exposing participants are more than a little shady.
However, there’s a major limiting factor in the trials now underway—all of them appear to be dependent on plasma introduced though IV treatment. This means participants must undergo a transfer of plasma in a healthcare center, which can take at least several minutes, and the number of treatments that each volunteer donor can produce is limited. Even if the trials turn out to be staggeringly effective, it’s hard to imagine that this technique could be used to protect more than a few thousand front-line workers. It certainly doesn’t seem like a treatment that could be applied to millions in advance of an available vaccine.
But there is another way.
Rather than a IV-based treatment, the antibodies in plasma can be further refined and concentrated to the point where they can be administered through an ordinary injection. As the Los Angeles Times reports, a pair of researchers—Dr. Michael Oxman and Dr. John Zaia—submitted a proposal to the government to being a trial of exactly this approach. But their request went unfunded. While $27 million was given to develop a pair of IV-based forms of COVID-19, none was provided for an injectable approach.
Oxman and Zaia made a second application for a clinical trial at UCSD, for an injection trial that would run side-by-side with the IV-based trial now underway. This trial would have used 5-millimeter vials of concentrated “immune globulin” (IG). This application was supported by other researchers, but it was also rejected.
The Times article collects a number of quotes showing the consternation of other medical experts, including Dr. Michael Joyner from the Mayo Clinic. “Beyond being a lost opportunity, this is a real head-scratcher,” said Joyner. “It seems obvious.” Those quoted included Dr. Anthony Fauci, who calls the idea of injectable IG “a very attractive concept.” However, Fauci does express concern that the efficacy of plasma treatments as a prophylactic treatment needs to be tested before an intramuscular shot is developed.
And that seems to be where things are stuck—no one wants to support the development of a shot until it’s clear that the IV-based plasma is effective. And prophylactic trials take months to demonstrate good results. That means that even the earliest of these trials are unlikely to produce definitive results before late August or September. Even if the intramuscular shots were given the go-ahead at that point, developing the treatment, determining the proper dose, and setting up large scale production could mean that the shots were not available until near the end of the year.
Which puts these shots squarely up against another obstacle: Vaccine developers. Most of the same companies that might potentially ramp up to produce of these shots in quantity, are already betting on development of a vaccine by early 2021. Putting resources toward development of something that is seen as a temporary patch seems like a distraction—or even competition—to the product they’re racing to market. Compounding that effect is the fact that “Operation Warp Speed” has already invested hundreds of millions to produce vaccines in advance of trials. They’re being produced right now. No money is available to produce the IG shots.
If effective, an IG shot could be made cheaply and administered by any nurse or assistant who can give an ordinary shot. If just 10% of those who have already recovered from COVID-19 in the United States could be persuaded to donate plasma, it would be enough for 13 million treatments. Those at potential risk, from doctors and nurses, to nursing home residents and workers, to teachers facing reopening schools, could all be protected in a matter of weeks. Only that solution is not being developed, and short of a deep-pocketed “angel” stepping in to make it happen, it’s unlikely this approach will be developed.
But there is another really good reason why it should be—the vaccine bet is far from a sure thing. The first vaccines off the line may prove ineffective, or may turn out to have unacceptable risks. Finding a final solution to COVID-19 may require months of additional trials, and societies around the world could find themselves mired in social distancing and reduced activity for an extended period … That is, unless they have a fallback; a preventative measure that’s easily made, easily administered, and capable of keeping critical workers safe while the bugs are worked out of a long term solution.
Early testing with plasma has found it to be safe. We don’t yet know if prophylactic use will be effective. But IG shots are easily made, easily scaled up, and represent the best known hope for immunity short of an effective vaccine. If someone has a few million dollars to invest in humanity, it’s hard to think of a better place to put it at the moment.