Neutralizing Antibody Responses in COVID-19 Convalescent Sera

Lee, William T; Girardin, Roxanne C; Dupuis, Alan P; Kulas, Karen E; Payne, Anne F; Wong, Susan J; Arinsburg, Suzanne; Nguyen, Freddy T; Mendu, Damodara Rao; Firpo-Betancourt, Adolfo; Jhang, Jeffrey; Wajnberg, Ania; Krammer, Florian; Cordon-Cardo, Carlos; Amler, Sherlita; Montecalvo, Marisa; Hutton, Brad; Taylor, Jill; McDonough, Kathleen A

Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT(50)) and high (PRNT(90)) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT(50)) and approximately 54% (PRNT(90)). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.