Characterizing Kinetics and Avidity of SARS-CoV-2 Antibody Responses in COVID-19 Greek Patients

Abstract

In-depth understanding of the immune response provoked by SARS-CoV-2 infection is necessary, as there is a great risk of reinfection and a difficulty in achieving herd immunity due to a decline in both antibody concentration and avidity. Avidity testing, however, could overcome variability in the immune response associated with sex or clinical symptoms, and thus differentiate between recent and past infections. In this context, here, we analyzed SARS-CoV-2 antibody kinetics and avidity in Greek hospitalized (26%) and non-hospitalized (74%) COVID-19 patients (N = 71) in the course of up to 15 months after their infection to improve the accuracy of the serological diagnosis in dating the onset of the infection. The results showed that IgG-S1 levels decline significantly at four months (p = 0.0239) in both groups of patients and are higher in hospitalized ones (up to 2.1-fold, p < 0.001). Additionally, hospitalized patients’ titers drop greatly and are equalized to non-hospitalized ones only at a time-point of twelve to fifteen months. Antibody levels of women in total remain more stable months after infection, compared to men. Furthermore, we examined the differential maturation of IgG avidity after SARS-CoV-2 infection, showing an incomplete maturation of avidity that results in a plateau at four months after infection. We also defined 38.2% avidity (sensitivity: 58.9%, specificity: 90.91%) as an appropriate “cut-off” that could be used to determine the stage of infection before avidity reaches a plateau.

Analysis of a German blood donor cohort reveals a high number of undetected SARS-CoV-2 infections and sex-specific differences in humoral immune response

“…Nevertheless, median RAI values were at a comparably low level during the whole study period. These findings are in line with those of other research groups, showing an incomplete avidity maturation pattern of SARS-CoV-2 IgG antibodies after natural infection [32][33][34]. In contrast, Struck et al show that two vaccination steps or the combination of vaccination and natural infection lead to the establishment of high avidity anti-SARS-CoV-2 IgG antibodies [34].…”

Differential avidity determination of IgG directed towards the receptor‐binding domain (RBD) of SARS‐CoV‐2 wild‐type and its variants in one assay: Rational tool for the assessment of protective immunity

“…Avidity maturation after SARS‐CoV‐2 infection or vaccination follows a pattern that is different from nearly all other viral infections, 10 as natural infection with SARS‐CoV‐2 does not regularly lead to the establishment of a high avidity IgG response. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 The limitation of the IgG response to low or intermediate avidity seems to be part of the specific biology of coronaviruses, 19 allowing for repeated waves of reinfection. 20 , 21 …”

“…9,10 Avidity maturation after SARS-CoV-2 infection or vaccination follows a pattern that is different from nearly all other viral infections, 10 as natural infection with SARS-CoV-2 does not regularly lead to the establishment of a high avidity IgG response. [11][12][13][14][15][16][17][18] The limitation of the IgG response to low or intermediate avidity seems to be part of the specific biology of coronaviruses, 19 allowing for repeated waves of reinfection. 20,21 "Incomplete" avidity maturation after SARS-CoV-2 infection is most likely due to the lack of sufficient antigen presentation for a sufficiently long time to drive the completion of the avidity maturation process.…”

The COVID-19 Pandemic Enhanced Virology Research in Greece

“…In this Special Issue, contributing research groups analyzed the kinetics and avidity of SARS-CoV-2 antibody responses in hospitalized and nonhospitalized COVID-19 patients [ 2 ], as well as the role of SARS-CoV-2 antigenemia/viremia in masking the ability of immunodiagnostic assays to detect humoral responses [ 3 ]. The structural analysis of the receptor-binding domain (RBD) of the spike (S) protein and angiotensin-converting enzyme (ACE2) presented a potential effectiveness of bisartans as SARS-CoV-2 inhibitors [ 4 ].…”