Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern
Maggie Li, Evan J. Beck, Oliver Laeyendecker, Yolanda Eby, Aaron A.R. Tobian, Patrizio Caturegli, Camille Wouters, Gregory R. Chiklis, William Block, Robert O. McKie, Michael J. Joyner, Timothy D. Wiltshire, Allan B. Dietz, Thomas J. Gniadek, Arell Shapiro, Anusha Yarava, Karen Lane, Daniel F. Hanley, Evan M. Bloch, Shmuel Shoham, Edward R. Cachay, Barry Meisenberg, Moisés A. Huamán, Yuriko Fukuta, Bela Patel, Sonya L. Heath, Adam C. Levine, James H. Paxton, Shweta Anjan, Jonathan M. Gerber, Kelly A. Gebo, Arturo Casadevall, Andrew Pekosz, David Sullivan
Abstract
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.