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

Manuylov, Victor A; Бургасова, О. А.; Борисова, О. В.; Smetanina, S.V.; Vasina, Daria V.; Grigoriev, Igor V.; Kudryashova, A. M.; Semashko, Maria; Cherepovich, Bogdan; Kharchenko, O.S.; Kleymenov, Denis A.; Mazunina, Elena P.; Tkachuk, Artem P.; Gushchin, Vladimir A.

doi:10.3390/v14030617

Cited by 16 publications

(14 citation statements)

References 39 publications

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“…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].…”

Section: Plos Onesupporting

confidence: 91%

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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

2022

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Seroprevalence studies can contribute to a better assessment of the actual incidence of infection. Since long-term data for Germany are lacking, we determined the seroprevalence of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in residual plasma samples of 3,759 German regular blood donors between July 2020 and June 2021. Over almost the entire study period, the incidences determined based on our data were higher than those officially reported by the Robert Koch Institute, the public health institute in Germany. Using our serological testing strategy, we retrospectively detected natural infection in 206/3,759 (5.48%; 95% confidence interval (CI): 4.77–6.25) individuals. The IgG seroprevalence ranked from 5.15% (95% CI: 3.73–6.89) in Lower Saxony to 5.62% (95% CI: 4.57–6.84) in North Rhine Westphalia. The analyses of follow-up samples of 88 seropositive blood donors revealed a comparable fast decay of binding and neutralizing anti-SARS-CoV-2 IgG antibodies. The antibody avidity remained at a low level throughout the whole follow-up period of up to 181 days. Interestingly, female donors seem to express a stronger and longer lasting humoral immunity against the new coronavirus when compared to males. Conclusion: Overall, our data emphasizes that seroprevalence measurements can and should be used to understand the true incidence of infection better. Further characterization of follow-up samples from seropositive donors indicated rapid antibody waning with sex-specific differences concerning the strength and persistence of humoral immune response.

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Section: Plos Onesupporting

confidence: 91%

“…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].…”

Section: Plos Onementioning

confidence: 99%

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

2022

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

Dapporto

Marchi

Leonardi

et al. 2022

Journal of Immunology Research

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Background. The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods. Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results. In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions. Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Bauer

Struck²,

Staschik³

et al. 2022

Journal of Medical Virology

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The avidity (binding strength) of IgG directed towards the receptor‐binding domain (RBD) of spike protein has been recognized as a central marker in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) serology. It seems to be linked to increased infection‐neutralization potential and therefore might indicate protective immunity. Using a prototype line assay based on the established recomLine SARS‐CoV‐2 assay, supplemented with RBD of the delta and the omicron variant, differential avidity determination of IgG directed towards RBD of wild‐type (WT) SARS‐CoV‐2 and distinct variants was possible within one assay. Our data confirm that natural SARS‐CoV‐2 infection or one vaccination step lead to low avidity IgG, whereas further vaccination steps gradually increase avidity to high values. High avidity is not reached by infection alone. After infection with WT SARS‐CoV‐2 or vaccination based on mRNA WT, the avidity of cross‐reacting IgG directed towards RBD of the delta variant only showed marginal differences compared to IgG directed towards RBD WT. In contrast, the avidity of IgG cross‐reacting with RBD of the omicron variant was always much lower than for IgG RBD WT, except after the third vaccination step. Therefore, parallel avidity testing of RBD WT and omicron seems to be mandatory for a significant assessment of protective immunity towards SARS‐CoV‐2.

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

Cited by 16 publications

References 39 publications

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

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

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

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

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