SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors

Benner, Sarah E; Patel, Eshan U; Laeyendecker, Oliver; Pekosz, Andrew; Littlefield, Kirsten; Eby, Yolanda; Fernandez, Reinaldo E; Miller, Jernelle; Kirby, Charles S; Keruly, Morgan; Klock, Ethan; Baker, Owen R; Schmidt, Haley A; Shrestha, Ruchee; Burgess, Imani; Bonny, Tania S; Clarke, William; Caturegli, Patrizio; Sullivan, David; Shoham, Shmuel; Quinn, Thomas C; Bloch, Evan M; Casadevall, Arturo; Tobian, Aaron A R; Redd, Andrew D

BACKGROUND: Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19 susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. METHODS: SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n=16 individuals) and a cross-sectional sample of convalescent plasma donors (n=130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. RESULTS: Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity was associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (spearman’s rho=0.386;p&0.001), than with anti-nucleocapsid IgG avidity (spearman’s rho=0.211;p=0.026). Increasing levels of anti-spike IgG avidity were associated with high NT(≥160) (adjusted prevalence ratio=1.58[95%CI=1.19-2.12]), independent of age, sex, and hospitalization. CONCLUSIONS: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.