A panel of the National Institutes of Health (NIH) concluded that “there are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.” The review by the COVID-19 Treatment Guidelines Panel comes shortly after the FDA issued an emergency-use authoriation (EUA) for convalescent plasma for the treatment of hospitalized patients with COVID-19.
The panel reviewed all available evidence from published and unpublished data on convalescent plasma for the treatment for COVID-19, including the FDA analyses that supported the EUA. Based on the review, the panel determined that convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19, echoing comments made by FDA chief scientist Denise Hinton when the EUA was announced.
No survival benefit
According to the NIH panel, the analysis on which the EUA was based found no difference in 7-day survival overall between patients who received convalescent plasma with high titers of SARS-CoV-2 neutralizing antibodies and those who received plasma with low titers. Results from a subset of hospitalized patients from the Mayo Clinic’s Expanded Access Program (EAP) showed that among patients who were not intubated, 11% of those who received convalescent plasma with high antibody titers died within seven days of transfusion compared with 14% of those who received convalescent plasma with low antibody titers. Meanwhile, among those who were intubated, there was no difference in 7-day survival.
The NIH panel noted that “although these data suggest that convalescent plasma with high antibody titers may be beneficial in non-intubated patients, uncertainty remains about the efficacy and safety of convalescent plasma due to the lack of a randomised control group and possible confounding in the Mayo Clinic’s EAP.” The panel added that antibody levels in currently available COVID-19 convalescent plasma are “highly variable,” while assays to determine the levels “remain limited.”
Agencies at odds
Commenting on the NIH panel’s review, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, denied that the new guidelines were a response to the FDA move. “The guidelines panel did not come out and criticize anyone or anything,” he said, adding that “they were neutral” on the use of convalescent plasma for COVID-19.
However, Eric Topol, executive vice president of Scripps Research Translational Institute, called it an “extraordinary moment,” adding “here you have different governmental agencies that are at odds.” Topol said “when you give pooled plasma, the chance that you will make a difference is very low. We don’t know if this is going to work.”
Topol also called on FDA Commissioner Stephen Hahn to explain why he misrepresented the data on convalescent plasma at the time the agency announced the EUA. At the time, Hahn said the treatment resulted in a 35% improvement in survival, although he later clarified “what I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”