Systems serology detects functionally distinct coronavirus antibody features in children and elderly
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Abstract
The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children ( n = 89), adults ( n = 98), elderly ( n = 57), and COVID-19 patients ( n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
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SciScore for 10.1101/2020.05.11.20098459: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Pathogen-specific antibodies were detected using phycoerythrin (PE)-conjugated mouse anti-human pan-IgG, IgG1-4, IgA1-2 (Southern Biotech), at 1.3μg/ml, 25μl per well. anti-human pan-IgG, IgG1-4suggested: NoneAntibody avidity assay: Avidity of antibodies in plasma samples was measured using urea as the chaotropic agent and only performed on samples with detectable RBD-specific antibodies (IgA and IgM). IgMsuggested: NoneSoftware and Algorithms Sentences Resources Endpoint titres were determined by interpolation from a sigmodial curve fit (all R-squared values >0.95; GraphPad Prism 8) as the reciprocal … SciScore for 10.1101/2020.05.11.20098459: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Pathogen-specific antibodies were detected using phycoerythrin (PE)-conjugated mouse anti-human pan-IgG, IgG1-4, IgA1-2 (Southern Biotech), at 1.3μg/ml, 25μl per well. anti-human pan-IgG, IgG1-4suggested: NoneAntibody avidity assay: Avidity of antibodies in plasma samples was measured using urea as the chaotropic agent and only performed on samples with detectable RBD-specific antibodies (IgA and IgM). IgMsuggested: NoneSoftware and Algorithms Sentences Resources Endpoint titres were determined by interpolation from a sigmodial curve fit (all R-squared values >0.95; GraphPad Prism 8) as the reciprocal dilution of plasma that produced ≥15% absorbance of the positive control. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)The overall multiplex dataset was analysed for normal distribution using the Shapiro-Wilk test by Prism 8 The data were further analysed by SPSS statistics 26 (IBM Corp.) using the Kruskal-Wallis one-way analysis with a Bonferroni correction to determine the p-values, differences between groups were considered significant at an adjusted p-value of 0.000035 (Extended data Table 2). SPSSsuggested: (SPSS, RRID:SCR_002865)Sequences were cut in Jalview 2.10.5 and subsequently aligned using T-Coffee with the default settings. T-Coffeesuggested: (T-Coffee, RRID:SCR_011818)Software: PCA, PLSDA, and PLSR models were completed using the Eigenvector PLS toolbox in Matlab. Matlabsuggested: (MATLAB, RRID:SCR_001622)PCA, PLSDA, and PLSR scores and loadings plots were plotted in Prism version. Prismsuggested: (PRISM, RRID:SCR_005375)Multiple sequence alignment was done in Jalview 2.10.5 and distance matrix for multiple alignments was done in Ugene 1.16.1 (http://ugene.unipro.ru; Unipro, Novosibirsk, Russia). Jalviewsuggested: (Jalview, RRID:SCR_006459)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.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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