On September 1, 2020, shortly after the U.S. Food and Drug’s Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP), the U.S. National Institutes of Health (NIH) issued a statement urging for more randomized controlled trials for CCP. The NIH Panel’s statement on CCP stressed the current lack of efficacy data based on “prospective, well-controlled, adequately powered randomized trials.” The FDA granted EUA for CCP based on data from the Expanded Access Program, which suggested limited efficacy for CCP in non-intubated patients—though the program lacked untreated controls. Data from at least four RCTs on the safety and efficacy of CCP are available, but several were stopped prematurely. The first RCT suggests CCP may be beneficial for non-critical patients but found no difference in most patients. The second RCT found no statistical difference between treatment groups, possibly because most patients already had high neutralizing antibody titers at the time of randomization. The third RCT included 81 patients at 14 hospitals in Spain and targeted patients within 12 days from symptom onset not on mechanical ventilation or high flow oxygen. None of the 38 patients transfused with CCP died or required ventilation; of the 43 patients receiving standard care, 4 (9.3%) died within 29 days and 2 (4.7%) required mechanical ventilation. However, a fourth RCT in India enrolled and randomized individuals to receive standard of care (n=229) or standard of care plus CCP (n=235) and found no difference between the two groups in mortality or progression to severe COVID-19. The results of CCP studies are heterogeneous and additional data are needed to determine which patient populations may benefit from CCP, the optimal time to administer CCP, and to identify the minimum neutralizing titers required.
- NIH Statement on Convalescent Plasma EUA. The COVID-19 Treatment Guidelines Panel’s Statement on the Emergency Use Authorization of Convalescent Plasma for the Treatment of COVID-19. September 1, 2020.
- Avendaño-Solà C, Ramos-Martinex A, Muñez-Rubio E, Ruiz-Antorán B, et al. Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial. MedRxIv September 1, 2020.
- Agarwal A, Mukherjee A, Kumar G, Chatterjee P, et al. Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel arms phase II multicenter randomized controlled trial (PLACID Trial). MedRxIv September 8, 2020.
- Li L, Zhang W, Hu Y, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA Published online June 3, 2020.
- Gharbharan A, Jordans C, GeurtsvanKessel C, den Hollander J, et al. Convalescent plasma for COVID-19. A randomized clinical trial. MedRxIv July 3, 2020.
