SARS-CoV-2 antibody signatures robustly predict diverse antiviral functions relevant for convalescent plasma therapy

Natarajan, Harini; Crowley, Andrew R.; Butler, Savannah E.; Xu, Shiwei; Weiner, Joshua A.; Bloch, Evan M.; Littlefield, Kirsten; Wieland-Alter, Wendy; Connor, Ruth I.; Wright, Peter F.; Benner, Sarah E.; Bonny, Tania S.; Laeyendecker, Oliver; Sullivan, David; Shoham, Shmuel; Quinn, Thomas C.; Larman, H. Benjamin; Casadevall, Arturo; Pekosz, Andrew; Redd, Andrew D.; Tobian, Aaron A.R.; Ackerman, Margaret E.

Convalescent plasma has emerged as a promising COVID-19 treatment. However, the humoral factors that contribute to efficacy are poorly understood. This study functionally and phenotypically profiled plasma from eligible convalescent donors. In addition to viral neutralization, convalescent plasma contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis and antibody-dependent cellular cytotoxicity against SARS-CoV-2. These activities expand the antiviral functions associated with convalescent plasma and together with neutralization efficacy, could be accurately and robustly from antibody phenotypes. These results suggest that high-throughput profiling could be used to screen donors and plasma may provide benefits beyond neutralization.