Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy

• DOI: 10.1016/j.xcrm.2022.100811
• Publication Date: 2022-10-24T05:53:12Z
• Authors: Jonathan D. Herman; Chuangqi Wang; John Stephen Burke; Yonatan Zur; Hacheming Compere; Jaewon Kang; Ryan Macvicar; Sabian Taylor; Sally Shin; Ian Frank; Don Siegel; Pablo Tebas; Grace H. Choi; Pamela A. Shaw; Hyunah Yoon; Liise-anne Pirofski; Boris D. Julg; Katharine J. Bar; Douglas Lauffenbu...; Galit Alter
• Keywords: Convalescent plasma; Coronavirus

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although neutralization is the predominant approach to benchmarking CCP efficacy, may also influence evolution of endogenous response. Using systems serology comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies hospitalized people with COVID-19 enrolled in randomized controlled trial (ClinicalTrials.gov: NCT04397757), we find that benefits are associated shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We greatest benefit participants low pre-existing anti-SARS-CoV-2 function CCP-induced immunomodulatory Fc glycan profiles N immunodominant persist for at least months. highlight potential mechanism action durable immunomodulation, outline optimal patient characteristics treatment, provide guidance development different class hyperinflammation-targeting agents.