Comprehensive analysis of SARS‐CoV‐2 antibody dynamics in New Zealand
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Abstract
Objectives
Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS‐CoV‐2 antibodies. This study explored antibody responses in recovered COVID‐19 patients in a setting where the probability of re‐exposure is effectively nil, owing to New Zealand's successful elimination strategy.
Methods
A triplex bead‐based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS‐CoV‐2 was developed. After establishing baseline levels with pre‐pandemic control sera ( n = 113), samples from PCR‐confirmed COVID‐19 patients with mild–moderate disease ( n = 189) collected up to 8 months post‐infection were examined. The relationship between antigen‐specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE‐2 interaction.
Results
While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4–8 months post‐infection. Anti‐RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti‐RBD IgG was demonstrated.
Conclusion
Antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
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SciScore for 10.1101/2020.12.10.20246751: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Using three different models the estimated t1/2 of 5-20 months for NAbs in this study is somewhat longer than 2-4 months calculated in other cohorts18,26, though all estimates have wide confidence intervals due to the inherent …
SciScore for 10.1101/2020.12.10.20246751: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Using three different models the estimated t1/2 of 5-20 months for NAbs in this study is somewhat longer than 2-4 months calculated in other cohorts18,26, though all estimates have wide confidence intervals due to the inherent limitations of modelling responses with marked individual heterogeneity. Nevertheless, all models place the NAb half-life at <2 years post-infection. Although NAbs are not yet a proven correlate of protection, and the impact of slow waning on susceptibility to re-infection is as yet unknown, NAbs and anti-S protein IgG have been associated with protection in recent outbreaks13,14, and in non-human primate studies28 suggesting a role for functional antibodies in SARS-CoV-2 immunity. Ultimately, large-scale vaccine trials will enable accurate determination of a correlate, and suggestions that two-dose Spike-based vaccines may induce more potent NAbs than natural infection29 are likely to result in responses of increased durability and longer half-life than estimated to date. Overall, this study provides a comprehensive view of SARS-CoV-2 antibodies over eight months. The strong correlation between anti-RBD IgG and NAbs, combined with the demonstration in this study and by others4,25,30 that anti-RBD can reliably be measured from dried blood fingerpick samples, provides feasibility for future SARS-CoV-2 immunokinetic studies that incorporate RBD-IgG based assays. The importance of conducting such studies at scale during vaccine roll-out is particularly rel...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.12.10.20246751: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources To detect the different antibody isotypes and subclasses, phycoerythrin (PE)-labelled donkey anti-human detection antibodies (IgG1, 2, 3 and 4, Southern Biotech; IgG/A/M, Jackson Immunoresearch) were diluted 1:75 and 1:80 in AB, respectively, then added to wells and incubated at room temperature for 35 min at 800rpm. anti-human detection antibodies ( IgG1 , 2 , 3suggested: None…SciScore for 10.1101/2020.12.10.20246751: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources To detect the different antibody isotypes and subclasses, phycoerythrin (PE)-labelled donkey anti-human detection antibodies (IgG1, 2, 3 and 4, Southern Biotech; IgG/A/M, Jackson Immunoresearch) were diluted 1:75 and 1:80 in AB, respectively, then added to wells and incubated at room temperature for 35 min at 800rpm. anti-human detection antibodies ( IgG1 , 2 , 3suggested: NoneExperimental Models: Cell Lines Sentences Resources Antigen coupling to beads SARS-CoV-2 RBD and the trimeric S protein antigens were recombinantly expressed and purified from HEK293T or HEK293F cells as previously described. HEK293Tsuggested: NoneHEK293Fsuggested: RRID:CVCL_6642)Software and Algorithms Sentences Resources Statistical analysis Data were analysed using Prism 8 (GraphPad) or R (version 4.0.2) within R Studio (version 1.2.5042) using packages rstatix (v 0.6.0; Kassambara, 2020) and the tidyverse (v1.3.0; Wickham, 2019). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
Using three different models the estimated t1/2 of 5-20 months for NAbs in this study is somewhat longer than 2-4 months calculated in other cohorts18,26, though all estimates have wide confidence intervals due to the inherent limitations of modelling responses with marked individual heterogeneity. Nevertheless, all models place the NAb half-life at <2 years post-infection. Although NAbs are not yet a proven correlate of protection, and the impact of slow waning on susceptibility to re-infection is as yet unknown, NAbs and anti-S protein IgG have been associated with protection in recent outbreaks13,14, and in non-human primate studies28 suggesting a role for functional antibodies in SARS-CoV-2 immunity. Ultimately, large-scale vaccine trials will enable accurate determination of a correlate, and suggestions that two-dose Spike-based vaccines may induce more potent NAbs than natural infection29 are likely to result in responses of increased durability and longer half-life than estimated to date. Overall, this study provides a comprehensive view of SARS-CoV-2 antibodies over eight months. The strong correlation between anti-RBD IgG and NAbs, combined with the demonstration in this study and by others4,25,30 that anti-RBD can reliably be measured from dried blood fingerpick samples, provides feasibility for future SARS-CoV-2 immunokinetic studies that incorporate RBD-IgG based assays. The importance of conducting such studies at scale during vaccine roll-out is particularly rel...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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