Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain
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Abstract
Background
Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach.
Methods
Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020.
Results
Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) ( p =0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19.
Conclusion
Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics.
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SciScore for 10.1101/2021.04.20.440593: (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 Measurement of antibodies: SARS-CoV-2 target antigens assays to measure IgG, IgA and IgM included the nucleocapsid (N) full-length (FL) and C-terminus (amino acid residues 340-416, CT), the spike (S) FL produced at CRG, S2 purchased from SinoBiological, and RBD donated by F. Krammer (Mount Sinai, NY). SARS-CoV-2 target antigens assays to measure IgGsuggested: NoneSoftware and Algorithms Sentences Resources The ggplot2 and pheatmap packages were used to perform graphs. ggplot2suggested: (ggplot2, RRID:SCR_014601)pheatmapsuggested: (pheatmap, RRID:SCR_016418)Results from OddPub: We did not detect open data. …
SciScore for 10.1101/2021.04.20.440593: (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 Measurement of antibodies: SARS-CoV-2 target antigens assays to measure IgG, IgA and IgM included the nucleocapsid (N) full-length (FL) and C-terminus (amino acid residues 340-416, CT), the spike (S) FL produced at CRG, S2 purchased from SinoBiological, and RBD donated by F. Krammer (Mount Sinai, NY). SARS-CoV-2 target antigens assays to measure IgGsuggested: NoneSoftware and Algorithms Sentences Resources The ggplot2 and pheatmap packages were used to perform graphs. ggplot2suggested: (ggplot2, RRID:SCR_014601)pheatmapsuggested: (pheatmap, RRID:SCR_016418)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:The main study limitation was the unavailability of pre-pandemic saliva samples that did not allow establishing the positivity threshold with saliva negative controls by the classical methods. Thus, we explored less standard FMM and EM algorithms to estimate the overall prevalence of SARS-CoV-2 exposure in the population studied. Models estimated positivity ranges that were much higher than seroprevalences estimated in contemporaneous surveys in the same geographical area (33–35). These algorithms may greatly overestimate the Ig positivity in saliva samples and/or saliva samples may be more sensitive to detect exposure to SARS-CoV-2, and/or classical methods to calculate positivity in serum/plasma may underestimate seroprevalence. More work is required to distinguish between these potential explanations, and to refine and validate these statistical approaches with datasets that have appropriate negative and positive controls. A related constraint was that we could not relate the antibody responses in saliva to current infection because there were very few RT-PCR positives, and that we could not compare saliva to serum responses due to the unavailability of blood samples. Therefore, our data could not be contrasted with the seroconversion or seroprevalence (36), considered the ‘gold standard’. In conclusion, antibody profiling in saliva samples with a multiplex technique represents a helpful and simpler tool in community-based surveys for determining saliva antibody conversion...
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:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
- 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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