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.
Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Saliva/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Phosphoproteins/immunology , Prevalence , Sensitivity and Specificity , Seroepidemiologic StudiesABSTRACT
BACKGROUND: Subclinical seizures are electrographic seizures that present without subjective or objective clinical symptoms. In tuberous sclerosis complex, it is not known whether subclinical seizures occur alone, forewarn, or coexist with clinical seizures. To address this knowledge gap, we studied the prevalence and evolution of subclinical seizures in tuberous sclerosis complex. METHODS: We retrospectively reviewed electroencephalography (EEG) data from our tuberous sclerosis complex clinic with subclinical seizures and clinical seizures in a blinded fashion. Based on EEG location and ictal pattern, subclinical seizures were classified as having a clinical counterpart from the same epileptogenic region (match) or not (no match). RESULTS: Of 208 children with tuberous sclerosis complex, 138 had epilepsy and available EEG data. Subclinical seizures were detected in 26 of 138 (19%) children. Twenty-four children had both subclinical seizures and clinical seizures captured on EEG. In 13 of 24, subclinical seizures were detected as a novel, not previously recorded seizure type. In these children, subclinical seizures preceded matching clinical seizures in 4 (31%) within a median time of 4.5 months (range 2-14), whereas 9 (69%) never had any matching clinical seizure. In 11 of 24 children, subclinical seizures were not novel and could be matched to a previously recorded clinical seizure. Matching seizure types were focal (n = 10, 67%), tonic (n = 2), epileptic spasms (n = 2), and status epilepticus (n = 1). CONCLUSIONS: Subclinical seizures occur in one-fifth of children with tuberous sclerosis complex and epilepsy, and match with clinical seizures in a small majority. In a third of patients presenting with a novel subclinical seizure, matching clinical seizures follow.
