Saliva SARS-CoV-2 Antibody Prevalence in Children

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ABSTRACT

COVID-19 patients produce circulating and mucosal antibodies. In adults, specific saliva antibodies have been detected. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We therefore assessed SARS-CoV-2-specific antibody prevalence in serum and saliva in children in the Netherlands. We assessed SARS-CoV-2 antibody prevalence in serum and saliva of 517 children attending medical services in the Netherlands (irrespective of COVID-19 exposure) from April to October 2020. The prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD), and nucleocapsid (N)-specific IgG and IgA were evaluated with an exploratory Luminex assay in serum and saliva and with the Wantai SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay in serum. Using the Wantai assay, the RBD-specific antibody prevalence in serum was 3.3% (95% confidence interval [CI]. 1.9 to 5.3%). With the Luminex assay, we detected heterogeneity between antibodies for S, RBD, and N antigens, as IgG and IgA prevalence ranged between 3.6 and 4.6% in serum and between 0 and 4.4% in saliva. The Luminex assay also revealed differences between serum and saliva, with SARS-CoV-2-specific IgG present in saliva but not in serum for 1.5 to 2.7% of all children. Using multiple antigen assays, the IgG prevalence for at least two out of three antigens (S, RBD, or N) in serum or saliva can be calculated as 3.8% (95% CI, 2.3 to 5.6%). Our study displays the heterogeneity of the SARS-CoV-2 antibody response in children and emphasizes the additional value of saliva antibody detection and the combined use of different antigens.

IMPORTANCE Comprehending humoral immunity to SARS-CoV-2, including in children, is crucial for future public health and vaccine strategies. Others have suggested that mucosal antibody measurement could be an important and more convenient tool to evaluate humoral immunity compared to circulating antibodies. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We show the heterogeneity of SARS-CoV-2 antibodies, in terms of both antigen specificity and differences between circulating and mucosal antibodies, emphasizing the additional value of saliva antibody detection next to detection of antibodies in serum.

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Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Marina Pollán, Beatriz Pérez-Gómez, Roberto Pastor-Barriuso … (2020)

Summary Background Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. Methods 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). Findings Seroprevalence was 5·0% (95% CI 4·7–5·4) by the point-of-care test and 4·6% (4·3–5·0) by immunoassay, with a specificity–sensitivity range of 3·7% (3·3–4·0; both tests positive) to 6·2% (5·8–6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years ( 10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1–92·1; both tests positive) to 91·8% (86·3–95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8–16·8) to 19·3% (17·7–21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1–24·9) to 35·8% (33·1–38·5). Only 19·5% (16·3–23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. Interpretation The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. Funding Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.

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Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

Li Li Guo, Lili Ren, Siyuan Yang … (2020)

Abstract Background The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. Methods The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. Results The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). Conclusions The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.

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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

Philip Brouwer, Tom Caniels, Karlijn van der Straten … (2020)

The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection as low as 0.007 μg/mL. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

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Author and article information

Contributors

Maya W. Keuning:

ORCID: https://orcid.org/0000-0003-3478-5339

Jennifer Dien Bard: Role: Editor

Journal

Journal ID (nlm-ta): Microbiol Spectr

Journal ID (iso-abbrev): Microbiol Spectr

Journal ID (publisher-id): spectrum

Title: Microbiology Spectrum

Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )

ISSN (Electronic): 2165-0497

Publication date (Electronic, pub): 15 September 2021

Publication date (Electronic, collection): Sep-Oct 2021

Publication date PMC-release: 15 September 2021

Volume: 9

Issue: 2

Electronic Location Identifier: e00731-21

Affiliations

[a ] Department of Pediatric Infectious Diseases, Rheumatology, & Immunology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

[b ] Department of Medical Microbiology and Infection Prevention, Amsterdam Institute of Infection and Immunity, Amsterdam UMC, University of Amsterdamgrid.7177.6, , Amsterdam, The Netherlands

[c ] Department of Pediatrics, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

[d ] Department of Pediatrics, Flevoziekenhuis, Almere, The Netherlands

[e ] Department of Pediatrics, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands

[f ] Department of Pediatrics, Amstellandziekenhuis, Amstelveen, The Netherlands

[g ] Department of Pediatrics, Zaans Medisch Centrum, Zaandam, The Netherlands

[h ] Department of Experimental Immunohematology, Sanquin Research, Amsterdam, The Netherlands

[i ] Landsteiner Laboratory, Amsterdam UMC, University of Amsterdamgrid.7177.6, , Amsterdam, The Netherlands

[j ] Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands

[k ] Department of Pediatrics, Tergooi Hospital, Blaricum, The Netherlands

Children's Hospital Los Angeles, University of Southern California

Author notes

Maya W. Keuning and Marloes Grobben contributed equally to this article. Author order was determined on the basis of contributions to study conception and design.

Citation Keuning MW, Grobben M, de Groen A-EC, Berman-de Jong EP, Bijlsma MW, Cohen S, Felderhof M, de Groof F, Molanus D, Oeij N, Rijpert M, van Eijk HWM, Koen G, van der Straten K, Oomen M, Visser R, Linty F, Steenhuis M, Vidarsson G, Rispens T, Plötz FB, van Gils MJ, Pajkrt D. 2021. Saliva SARS-CoV-2 antibody prevalence in children. Microbiol Spectr 9:e00731-21. https://doi.org/10.1128/Spectrum.00731-21.

Author information

Maya W. Keuning https://orcid.org/0000-0003-3478-5339

Marit J. van Gils https://orcid.org/0000-0003-3422-8161

Article

Publisher ID: 00731-21 Publisher ID: spectrum.00731-21

DOI: 10.1128/Spectrum.00731-21

PMC ID: 8557814

PubMed ID: 34523985

SO-VID: d83c5d52-97ad-4f2f-8727-938ceda59f20

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

History

Date received : 30 June 2021

Date accepted : 12 August 2021

Page count

supplementary-material: 1, Figures: 5, Tables: 0, Equations: 0, References: 43, Pages: 11, Words: 7063

Funding

Funded by: Contribute Foundation;

Award Recipient : Dasja Pajkrt Award Recipient : Maya W. Keuning

Funded by: AMC Fellowship;

Award Recipient : Marit J. van Gils

Funded by: Bill & Melinda Gates Foundation;

Award ID: INV-024617

Award Recipient : Marit J. van Gils

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cover-date September/October 2021

Keywords: sars-cov-2,antibodies,children,humoral immunity,prevalence,saliva

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Keywords: sars-cov-2, antibodies, children, humoral immunity, prevalence, saliva

Saliva SARS-CoV-2 Antibody Prevalence in Children

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Novel Coronavirus Disease COVID-19

Most cited references 41

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

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