key: cord-318006-9op556q2
authors: Luo, Y. R.; Chakraborty, I.; Yun, C.; Wu, A. H. B.; Lynch, K. L.
title: Kinetics of SARS-CoV-2 Antibody Avidity Maturation and Association with Disease Severity
date: 2020-08-02
journal: nan
DOI: 10.1101/2020.07.30.20165522
sha: 
doc_id: 318006
cord_uid: 9op556q2

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was studied. The IgG avidity assay used a novel label-free immunoassay technology to test IgG against the virus spike protein receptor-binding domain (RBD). The technology, thin-film interferometry (TFI), is able to sense the formation of immune complex on a sensing probe without attaching a reporter (enzyme, fluorophore, etc.). It was found that there was a strong correlation between IgG antibody avidity and days since symptom onset (p < 0.0001). In addition, peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset (1-4 weeks) and thereafter (p<0.0001). The findings are consistent for what has been reported for SARS-CoV. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody-mediated immune enhancement triggered by suboptimal antibodies may not play a role in COVID-19 disease progression and severity.

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was studied. The IgG avidity assay used a novel label-free immunoassay technology to test IgG against the virus spike protein receptorbinding domain (RBD). The technology, thin-film interferometry (TFI), is able to sense the formation of immune complex on a sensing probe without attaching a reporter (enzyme, fluorophore, etc.). It was found that there was a strong correlation between IgG antibody avidity and days since symptom onset (p < 0.0001). In addition, peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset (1-4 weeks) and thereafter (p<0.0001). The findings are consistent for what has been reported for SARS-CoV. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody-mediated immune enhancement triggered by suboptimal antibodies may not play a role in COVID-19 disease progression and severity.

In the race to identify correlates of COVID-19 immunity, the focus has been on characterizing the production of SARS-CoV-2 antibodies. Most immunocompetent individuals with symptomatic infections develop detectable SARS-CoV-2 antibodies within 2 weeks of symptom onset (1). The SARS-CoV-2 IgG antibody response is more robust in severe cases of COVID-19 at all time-points after seroconversion (1) . Preliminary findings suggest that the magnitude of the response correlates with virus neutralizing power, but some hypothesize that the antibodies could promote disease progression (2) . Influential factors in the distinction between protective antibodies and those that promote pathology include antibody isotype, All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 2, 2020. presented as a percentage. The study was approved by the Institutional Review Board of the All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 2, 2020. . https://doi.org/10.1101/2020.07.30.20165522 doi: medRxiv preprint University of California. All testing was performed on remnant serum samples collected for routine clinical testing and stored at -20°C prior to testing.

Using least squares linear regression analysis, there was a strong correlation between IgG avidity and days since symptom onset (p < 0.0001) (Fig. 1A) . SARS-CoV-2 IgG avidity did not correlate with IgG concentration, as measured previously using a quantitative immunoassay (1).

The kinetics of IgG avidity maturation in 13 patients for whom serial samples (>3) were available is shown in Fig 1B. In all patients, IgG avidity increased over time. Peak measurements, which included the last measurement per 7-day interval per patient, were used to compare IgG avidity by disease severity. Peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset (1-4 weeks) and thereafter (p<0.0001) (Fig. 1C ).

To our knowledge this is the first study to evaluate antibody avidity maturation in For other viruses, high-avidity antibodies capable of blocking receptor binding typically do not induce disease progression. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody-mediated immune enhancement triggered by suboptimal antibodies may not play a role in COVID-19 disease progression and severity. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 2, 2020. . https://doi.org/10.1101/2020.07.30.20165522 doi: medRxiv preprint Further studies are needed to determine if the antibody response, both IgG concentration and avidity, correlate with virus neutralization and persist over time. The avidity method described here makes use of the label-free immunoassay technology, thin-film interferometry, which allows for direct observation of the time course of immune complex formation. This technology could be a valuable tool for continued characterization of the adaptive immune response to SARS-CoV-2.

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Clinical utility of avidity assays

Development of label-free immunoassays as novel solutions for the measurement of monoclonal antibody drugs and antidrug antibodies

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 2, 2020. All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 2, 2020. . https://doi.org/10.1101/2020.07.30.20165522 doi: medRxiv preprint