Comparison of SARS-CoV-2 seroconversion in children with chronic diseases with healthy children and adults during the first waves of the COVID-19 pandemic

Abstract

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is clinically diverse, and children have a low risk of developing severe coronavirus disease 2019 (COVID-19). However, children with chronic diseases have a potentially increased risk.

Methods: We performed a prospective surveillance study with longitudinal serum SARS-CoV-2 anti-nucleocapsid antibody quantification and questionnaires in pediatric tertiary care patients during the first waves of the COVID-19 pandemic (November 2020-September 2021). The results were compared with those of healthy children and adults from the same geographic area.

Results: We obtained 525 samples from 362 patients (M/F ratio of 1.3:1; median age of 11.1 years) comprising children with immune-suppressive or immune-modulating drugs (32.9%), inborn errors of immunity (23.5%), type 1 diabetes mellitus (15.2%), and rheumatic diseases (11.9%). A total of 51 (9.7%) samples were seropositive among 37/351 children (10.5%). Seropositivity increased from 5.8% in November-December 2020 to 21.6% in July-September 2021. Compared with adults, a longitudinal analysis revealed reduced seroprevalence but similar kinetics as in children from the same country. Demographic or social variables and disease characteristics did not correlate with seropositivity. Being obese and household contact with COVID-19-infected individuals significantly increased the odds of infection. The majority of seropositive patients had mild symptoms (21/37). One-third were asymptomatic and/or unaware of having COVID-19 (10/37). Four patients (4/37) needed hospitalization, with good clinical outcomes.

Conclusions: Although harboring a chronic disease, we observed a low SARS-CoV-2 incidence in a cohort of pediatric tertiary care patients, comparable with healthy children during the first year of the pandemic. Infection was mostly associated with mild symptoms.

Keywords: COVID-19; SARS-CoV-2; chronic diseases; serology; tertiary care pediatric patients.

Figure 1

Serological assessment of a cohort of tertiary pediatric patients. Individual samples (n = 525) obtained from 362 pediatric patients were analyzed for the presence of antibodies against the nucleocapsid (N) antigen of SARS-CoV-2. The proportion and percentage of serum samples with an OD ratio greater or equal to 0.9 are denoted in red. Patients were included during the first 4 months of the study (November 2020–February 2021), after which they were eligible for follow-up samples until September 2021.

Figure 2

Evolution of percentage of seropositive individuals in this study (blue) as compared with surveillance pediatric and adult populations from the same region/country. National surveillance data based on blood samples from cohorts of healthcare workers (pink) and blood donors (light purple) are plotted until the COVID-19 vaccination campaign was initiated in Belgium (Jan 2021) (–22). For the adult population, a subcohort of non-vaccinated individuals from another national study monitoring IgG in saliva specimens of healthy adults (SalivaHIS) is shown (dark purple) (–24). To compare our pediatric data, a surveillance study measuring seroconversion in pupils from schools is plotted (green) (–19). For this healthy pediatric cohort, we used the readily available and substratified data from the subnational level (Flanders) and concerning children from primary school, to maximally match our cohort of patients. For the epidemiological context, the number of PCR-confirmed infections as counted by the national health institute is mentioned (red, plotted on the right axis) (21). PCR-confirmed infections during the first months of the pandemic should be considered a substantial underestimation (lack of available testing); also, pediatric infections are underrepresented (adapted testing policy from young children in ambulatory setting). In Belgium, for healthy children, schools were re-opened on 15 May 2020. Children with primary or secondary immunodeficiency (considered “high risk” for severe infection) were recommended to stay home longer, with the absence of public recommendations from September 2020 onward.

Figure 3

Prospective monitoring of positive samples from our cohort of tertiary pediatric patients. OD ratios of anti-N SARS-CoV-2 serology are plotted in function of days since the first positive test. Paired samples from the patients in this study are shown in red. In blue, the median decay of anti-N in healthy individuals (−0.26/month), as reported by Gallais et al., is presented as a comparator.

Figure 4

Predictors for SARS-CoV-2 seroconversion in tertiary pediatric patients. Proportion of seropositive patients in this pediatric tertiary cohort, stratified for demographical and clinical variables (A), social behavior and household characteristics (B), and exposure to SARS-CoV-2 (C). ORs and 95% CIs were calculated as conditional maximum-likelihood estimate. P-values were assessed as two-tailed mid P Exact. Graphs display odds ratios (dot) and 95% CI (line), where significant results are displayed in red. Because of a logarithmic scale, variables including zero are denoted with an arrow. CLD, chronic liver disease.