My presumption that today’s “major therapeutic breakthrough” announcement with President Trump and Secretary Azar will be about blood plasma as a #COVID19 treatment. It is a refrain that is still echoing from our Hydroxychloroquine experience and one, apparently, that this Administration is willing to sing again. Like Hydroxychloroquine in March, convalescent plasma has promise but has not been rigorously studied and, therefore, is not ready for this (literal) primetime announcement.
But, backing up, I was a bit surprised this week when the U.S. Food and Drug Administration halted its imminent Emergency Use Authorization of convalescent plasma in the treatment of hospitalized COVID-19 patients. This decision occurred after infectious disease experts, including Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), H. Clifford Lane, Clinical Director of NIAID, and Francis S. Collins, MD, director of the National Institutes of Health, warned the agency that data on its efficacy were lacking.
The use of convalescent plasma dates back to the 1890’s when antibodies were first used to protect against bacterial toxins before the introduction of antibiotics. Modern formulations of intravenous immunoglobulin (IVIG), pooled from thousands of healthy donors, is still used today to prevent viral infections in certain patient populations. As a physician treating COVID-19 patients, I have been reasonably enthusiastic about the potential of convalescent serum in the treatment of severe cases. In fact, I have encouraged patients of mine that have recovered clinically from COVID-19 and have negative follow-up testing to reach out to the Red Cross and donate to this effort.
To date in the US, more than 66,000 individuals have received convalescent plasma, most under a “compassionate use” basis for those with severe illness. The difficulty in this effort is that no control groups have been run – in other words, those receiving convalescent plasma were not matched with another of similar age, gender and underlying conditions who did not receive this treatment. But, unlike Hydroxychloroquine, it does appear that this treatment is generally safe (Reference: Joyner, M. J. et al. J. Clin. Invest. https://doi.org/10.1172/JCI140200 (2020).
Given that large, randomized, placebo controlled clinical trials do not exist, we are left trying to piece together evidence from smaller tests. One recent study combined data from more than 800 participants across a dozen studies – the treatment decreasedCOVID-19 mortality from 26% to 13% among those with severe illness (Reference: Joyner, M. J. et al. Preprint at medRxiv. https://doi.org/10.1101/2020.07.29.20162917 (2020).
So what we are left with is a fuzzy picture just now starting to come into focus. So (going out on a limb), today’s announcement of a “major breakthrough” is unsupported. Further, convalescent serum only functions as a placeholder until a more specific treatment modality (antiviral for example) or vaccine is developed.
So we will wait for additional data – and once again the United Kingdom’s National Health Service may ride to the Epidemiologic rescue. The large RECOVERY trial, which is testing several therapies, including convalescent plasma, in people hospitalized with COVID-19. But the first surge of the pandemic in the UK has largely passed, so researchers do not expect to have results until later in 2020.
“There is good science behind convalescent plasma and a good reason for thinking that it may turn out to be an effective treatment,” Dr. Martin Landray, a UK Epidemiologist, has said. “But the bottom line is that we don’t have enough data to know.”