Avidity of IgG to SARS-CoV-2 RBD as a Prognostic Factor for the Severity of COVID-19 Reinfection

Abstract

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient’s risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05).

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].…”

“…The study of Manuylov et al recently showed that the avidity of anti-SARS-CoV-2 IgG antibodies can be used as a prognostic factor for the severity of COVID-19 reinfection. A low avidity index (� 40%) following the initial infection enhances the risk of a severe COVID-19 course in case of SARS-CoV-2re-infection significantly [32].…”

Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination

“…In a previous study [ 31 ], this reduced neutralizing antibody response was observed when these same samples were tested for the alpha (B.1.1.7), beta (B.1.351), and gamma (P.1) variants and was ascribed to the substantial divergence between the infecting strain (wt) and the variants tested. The reduction in neutralizing activity against Omicron and other VoCs was probably due to low affinity, and therefore low avidity, antibodies, confirming that only high-avidity antibodies are involved in virus neutralization, since they can effectively compete with angiotensin-converting enzyme 2 (ACE2) for binding to the RBD [ 11 , 32 ].…”

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

“…In line with this finding, stronger avidity maturation was associated with disease resolution. Finally, Manuylov et al presented data that indicated that the presence of low‐avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient's risk of developing COVID‐19 in a severe form is significantly increased 32 . Therefore, though it is certainly not possible to exclude future SARS‐CoV‐2 infection based on the presence of high avidity IgG directed towards RBD, the lack of high avidity IgG despite vaccination might be regarded as an indication of potential risk.…”