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

Abstract

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 were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 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.

Keywords: SARS-CoV-2; anti-nucleocapsid; anti-spike; avidity; convalescent plasma.

Figure 1.

Longitudinal trajectories in anti-spike and anti-nucleocapsid SARS-CoV-2 IgG titers and avidity responses in hospitalized COVID-19 patients by time from symptom onset. Plasma samples taken over course of hospitalization were used to evaluate total antibody titers and antibody avidity (DC₅₀). Each patient is represented by a different color. (A) Anti-spike IgG titers; (B) anti-spike IgG avidity; (C) anti-nucleocapsid titers, and (D) anti-nucleocapsid IgG avidity were measured over days since symptom onset. Antibody avidity is indicated by calculated dissociation constant (DC₅₀) where concentration of urea results in 50% of signal loss. Antibody titers are indicated by semiquantitative arbitrary units (AU) calculated from corrected OD (Euroimmun) or direct ODn values (EDI). Abbreviations: COVID-19, coronavirus disease 2019; EDI, Epitope Diagnostics Inc.; IgG, immunoglobulin G; OD, optical density; ODn, normalized optical density; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Anti-spike SARS-CoV-2 IgG avidity responses (DC₅₀) by epidemiologic characteristics among potential COVID-19 convalescent plasma donors. Anti-spike IgG avidity was evaluated compared to (A) sex, (B) age, (C) race/ethnicity, and (D) hospitalization. Red diamonds (A, C, D) indicate the arithmetic mean of avidity DC₅₀ values for a given group and (B) avidity DC₅₀ values are denoted by green triangles for males and grey circles for females. Abbreviations: COVID-19, coronavirus disease 2019; DC₅₀, 50% dissociation constant; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Anti-nucleocapsid SARS-CoV-2 IgG avidity responses (DC₅₀) by epidemiologic characteristics among potential COVID-19 convalescent plasma donors. Anti-nucleocapsid IgG avidity was evaluated compared to (A) sex, (B) age, (C) race/ethnicity, and (D) hospitalization. Blue diamonds (A, C, D) indicate the arithmetic mean of avidity DC₅₀ values for a given group and triangles (B) denote avidity DC₅₀ values for males and circles denote avidity DC₅₀ values for females. Abbreviations: COVID-19, coronavirus disease 2019; EDI, Epitope Diagnostics Inc.; DC₅₀, 50% dissociation constant; IgG, immunoglobulin G; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 4.

Correlations of anti-spike and anti-nucleocapsid SARS-CoV-2 IgG responses with neutralizing antibody titers among potential COVID-19 convalescent plasma donors. Correlations between neutralizing antibody titer AUC values and (A) anti-spike IgG titers, (B) anti-spike IgG avidity, (C) anti-nucleocapsid IgG titers, and (D) anti-nucleocapsid avidity were examined using Spearman correlation coefficient and nonparametric LOWESS curves. Antibody avidity is indicated by calculated dissociation constant (DC₅₀) where concentration of urea results in 50% of signal loss. Antibody titers are indicated by arbitrary units (AU) calculated from corrected OD (Euroimmun) or direct ODn values (EDI). Abbreviations: AUC, area under the curve; COVID-19, coronavirus disease 2019; EDI, Epitope Diagnostics Inc.; IgG, immunoglobulin G; ODn, normalized optical density; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.