Differences in systemic and mucosal SARS-CoV-2 antibody prevalence in a prospective cohort of Dutch children

Abstract

BackgroundAs SARS-CoV-2 will likely continue to circulate, low-impact methods become more relevant to monitor antibody-mediated immunity. Saliva sampling could provide a non-invasive method with reduced impact on children. Studies reporting on the differences between systemic and mucosal humoral immunity to SARS-CoV-2 are inconsistent in adults and scarce in children. These differences may be further unraveled by exploring associations to demographic and clinical variables.MethodsTo evaluate the use of saliva antibody assays, we performed a cross-sectional cohort study by collecting serum and saliva of 223 children attending medical services in the Netherlands (irrespective of SARS-CoV-2 exposure, symptoms or vaccination) from May to October 2021. With a Luminex and a Wantai assay, we measured prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid-specific IgG and IgA in serum and saliva and explored associations with demographic variables.FindingsThe S-specific IgG prevalence was higher in serum 39% (95% CI 32 – 45%) than in saliva 30% (95% CI 24 – 36%) (P ≤ 0.003). Twenty-seven percent (55/205) of children were S-specific IgG positive in serum and saliva, 12% (25/205) were only positive in serum and 3% (6/205) only in saliva. Vaccinated children showed a higher concordance between serum and saliva than infected children. Odds for saliva S-specific IgG positivity were higher in girls compared to boys (aOR 2.63, P = 0.012). Moreover, immunocompromised children showed lower odds for S- and RBD-specific IgG in both serum and saliva compared to healthy children (aOR 0.23 – 0.25, P ≤ 0.050).ConclusionsWe showed that saliva-based antibody assays can be useful for identifying SARS-CoV-2 humoral immunity in a non-invasive manner, and that IgG prevalence may be affected by sex and immunocompromisation. Differences between infection and vaccination, between sexes and between immunocompromised and healthy children should be further investigated and considered when choosing systemic or mucosal antibody measurement.

Clinical and Analytical Performance of ELISA Salivary Serologic Assay to Detect SARS-CoV-2 IgG in Children and Adults

“…Firstly, the percentage of positivity to anti-SARS-CoV-2 N/S IgG was lower in children than in adults. These results are consistent with findings from Keuning et al [ 32 ], who suggested that the elevated prevalence of positivity in serum compared with saliva could be partially explained by time kinetics and demographic differences. Secondly, adult patients reported higher SARS-CoV-2 antibody titers than children in both the salivary and serum samples.…”

Endemic Human Coronavirus-Specific Nasal Immunoglobulin A and Serum Immunoglobulin G Dynamics in Lower Respiratory Tract Infections

“…Virus-specific nasal and saliva antibodies are significantly correlated with each other after SARS-CoV-2 infection [ 26 ]. The correlation between SARS-CoV-2-specific antibodies in serum and saliva was also reported by a cohort study of Dutch children, irrespective of SARS-CoV-2 exposure, symptoms, or vaccinations [ 27 ]. Of note, saliva antibodies decline earlier than serum antibodies in vaccinated and unvaccinated individuals [ 26 , 28 ].…”

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program

“…Briefly, the quantitative Luminex assay was used to measure S-specific IgG and nucleocapsid (N) specific IgG, with results expressed as international Binding Antibody Units per mL (BAU/ml) ( 21 , 22 ). Participants with S-specific IgG above 44.8 BAU/ml were considered seropositive ( 23 ). Nucleocapsid (N)-specific IgG antibodies were analyzed to identify participants who contracted COVID-19 before or during the study.…”

“…Nucleocapsid (N)-specific IgG antibodies were analyzed to identify participants who contracted COVID-19 before or during the study. We selected a cutoff value with 100% specificity, measured in pre-pandemic sera from healthy donors, to minimize the possibility of false-positive results due to administration of (low levels of) N-specific antibodies in IGRT ( 23 , 24 ). Therefore, an infection with SARS-CoV-2 was defined as a history of a positive PCR test, positive antigen test, and/or an N-specific IgG titer above 42.2 BAU/ml.…”