Why was the therapeutic use of serum from COVID-19 patients not approved by the FDA?

Source; the Mayo Clinic.

Convalescent serum (blood plasma) from recovered COVID-19 patients has been touted as a treatment for others with the disease. This week, however, the FDA delayed a decision about authorizing emergency use of convalescent serum as a therapy. The data just wasn’t there to prove that it had any benefit for treating COVID-19 patients.

One of the first ideas for the treatment of COVID-19 was to use the blood of recovered individuals to treat newly diagnosed patients. The concept is that people who have recovered from COVID-19 will have antibodies (proteins) in their blood that helped them resolve the infection. The antibodies in the liquid component of recovered patients’ blood (convalescent serum or plasma) should help acutely ill patients neutralize the COVID-19 virus and recover. It’s an approach to treating infections that has been around for over 100 years. 

This approach has enthusiastic supporters, including prominent survivors of COVID-19 (Tom Hanks!) who have donated their blood to the cause. The Mayo Clinic and the American Red Cross were also supportive. In addition, an effort by a consortium of 50 hospitals and universities called the National COVID-19 Convalescent Plasma Project even provides a website for patients, healthcare providers, and potential blood donors. An article by prominent physicians Arturo Casadevall of the Johns Hopkins School of Public Health and Liise-anne Pirofski of Albert Einstein Medical College championed the approach as a treatment for COVID-19. 

Despite the widespread enthusiasm, there is still no definitive data showing that plasma treatments are effective for people with COVID-19. A recent non-peer-reviewed study posted online reported on more than 30,000 patients receiving convalescent plasma; it showed that the more antibodies there were in a particular batch of convalescent plasma, the more effective the plasma was in preventing death. 

Unfortunately, the study did not have a control group receiving an injection of non-COVID-19 plasma, so that it’s difficult to make firm conclusions about the results. Other studies have failed to show a definitive benefit. This is eerily similar to what happened with hydroxychloroquine–great enthusiasm followed by no real evidence of efficacy.

Despite this, there were reports that the FDA , which is responsible for approving COVID-19 therapies, was close to granting emergency use authorization for convalescent plasma, when several senior officials at the National Institutes of Health raised objections. The NIH scientists argued that the evidence for the treatment’s efficacy was too minimal to warrant approval. Their objection won the day.

To show how difficult it might be to use antibodies like the ones found in the blood of recovered patients to prevent COVID-19 infection, an article in this week’s Science Magazine used a monoclonal antibody designed from recovered patients’ serum to prevent COVID-19 infection in hamsters. In this situation, all the antibodies are the same and bind to a single spot on the binding (spike) protein of COVID-19. The best antibody they could make required a 16.5 mg/Kg dose given right before challenge to protect a hamster. That would equal a ONE GRAM of pure, monoclonal antibody to protect a human, an amount that could never be achieved by serum transfer in humans. Also, even 1/10th of that dose did not blunt an infection.

Results of Guinea pig challenge required very high amounts of antibody given just one day before virus challenge to prevent COVID-19 in hamsters. Dropping the dose 30 or 50 fold totally removed the protection. (Science Magazine)

Emergency use authorization would have created a situation similar to hydroxychloroquine, where an approach would be approved and widely used as a therapy without proof. Doctors and patients who want plasma therapy can still access it under a program that allows for compassionate use as a last resort. But not being approved by the FDA is significant: It will encourage a definitive study to prove the value of convalescent serum therapy for Covid-19. 

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

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