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 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.

The serological response to SARS corona virus-2 is characterized by frequent incomplete maturation of functional affinity (avidity)

“…This feature correlates with the finding that the humoral immune response is often higher and more stable in patients with severe disease compared to control patients that only developed mild symptoms (11). It is also in line with the findings by Benner et al (33), who reported on a relative increase in avidity of IgG towards SARS CoV-2 in hospitalized patients.…”

“…These data confirm that the immune response towards SARS CoV-2 proteins shows an initial rise in avidity, reaching varying low to intermediate values, followed by cessation of further continuation of avidity maturation. A general low avidity of IgG towards SARS CoV-2 proteins has also been reported by other groups (13,14,33,34) though these authors did not recognize the specific kinetics of avidity maturation with its initial onset, followed by abrogation of maturation. Figure 3 illustrates the abrogation of avidity maturation in a characteristic case.…”

“…As a consequence, protection towards reinfection at a later time point is likely to be more efficient. The findings of a strict correlation between neutralizing potential of IgG directed towards SARS CoV-2 S1 protein/RBD and its avidity (33,34) is supporting this idea, though the overall avidity did not reach high values.…”

Serological Assessment of COVID-19 Patients in Brazil: Levels, Avidity, and Subclasses of IgG Against RBD

“…Although our study has limited data on temporal dynamics (< 45 days) to correlates SARS-CoV-2 antibody avidity with the illness severity, it was observed that the majority of patients who had symptoms showed low avidity. Our data is by what was reported to SARS-CoV-2 infection with low IgG antibody avidity during the 50 days after symptoms onset 42 , however, evaluating antibodies against nucleoprotein 55 , and to SARS-CoV-2 anti-spike and antinucleoprotein, that reached the avidity peak at 21 after days of symptoms onset, during a study period median of 45days 42 .…”

“…At the same time, IgG2 and IgG4 are less detectable in patients sera 29 , suggesting that IgG subclasses as an important marker to distinguish disease timepoint and, perhaps, disease severity. Other factors can also contribute to the understanding of humoral responses to SARS-CoV-2 and the role of neutralizing antibodies in the convalescent plasma of donors, such as an association between antibody neutralizing titers and antibody avidity 42 . Antibodies produced by patients that recovered from coronavirus disease 2019 (COVID-19) have been used as a "molecular framework" to design antibody-based therapies 43 .…”