Abstract
Objective
Characterizing the seroprevalence of SARS-CoV-2 antibodies in children is needed to optimize the COVID-19 public health response. We quantified the seroprevalence of SARS-CoV-2 infection-acquired antibodies and vaccine-acquired antibodies among children receiving primary care in Toronto, Canada.
Methods
We conducted a longitudinal cohort study between January 2021 and November 2022 in healthy children aged 0–16 years receiving primary care in Toronto. The primary and secondary outcomes were seroprevalence of SARS-COV-2 infection-acquired antibodies and vaccine-acquired antibodies ascertained from finger-prick dried blood spots. Samples were tested using an enzyme-linked immunosorbent assay for antibodies to full-length spike trimer and nucleocapsid. We explored sociodemographic differences with Firth’s penalized generalized estimating equations.
Results
Of the 475 participants, 50.1% were girls and mean age was 6.4 years (SD = 3.2). We identified 103 children seropositive for infection-acquired antibodies, with a crude seroprevalence that rose from 2.6% (95%CI 1.39–4.92) from January to July 2021 to 50.7% (95%CI 39.5–61.8) by July to November 2022. Seroprevalence of vaccine-acquired antibodies was 45.2% by July to November 2022 (95%CI 34.3–56.58). No differences in sociodemographic factors (age, sex, income, or ethnicity) were identified for infection-acquired antibodies; however, children with vaccine-acquired antibodies were more likely to be older, have mothers with university education, and have mothers who had also been vaccinated.
Conclusion
Our results provide a benchmark for seroprevalence of SARS-CoV-2 antibodies in children in Toronto. Ongoing monitoring of the serological status of children is important, particularly with the emergence of new variants of concern, low vaccine coverage, and discontinuation of PCR testing.
Supplementary Information
The online version contains supplementary material available at 10.17269/s41997-024-00916-3.
Keywords: SARS-CoV-2, Seroprevalence, Children, Primary care, Antibody, Toronto, COVID-19, Vaccination
Résumé
Objectif
Caractériser la séroprévalence des anticorps du SRAS-CoV-2 chez les enfants est nécessaire pour optimiser la réponse de santé publique à COVID-19. Nous avons quantifié la séroprévalence des anticorps acquis par l’infection au SRAS-CoV-2 et des anticorps acquis par le vaccin chez les enfants recevant des soins primaires à Toronto, au Canada.
Méthodes
Nous avons mené une étude de cohorte longitudinale entre janvier 2021 et novembre 2022 auprès d’enfants en bonne santé âgés de 0 à 16 ans recevant des soins primaires à Toronto. Les résultats principaux et secondaires étaient la séroprévalence des anticorps acquis par l’infection du SRAS-CoV-2 et des anticorps acquis par le vaccin déterminés à partir de taches de sang séché par piqûre au doigt. Les échantillons ont été testés à l’aide d’un test immuno-enzymatique pour détecter les anticorps dirigés contre le trimère de pointe complet et la nucléocapside. Nous avons exploré les différences sociodémographiques à l’aide des équations d’estimation généralisées pénalisées de Firth.
Résultats
Sur les 475 participants, 50,1 % étaient des filles et l’âge moyen était de 6,4 ans (ET = 3,2). Nous avons identifié 103 enfants séropositifs aux anticorps acquis lors d’une infection, avec une séroprévalence non ajusté qui est passée de 2,6 % (IC 95% : 1,39–4,92) de janvier à juillet 2021 à 50,7 % (IC 95% : 39,5–61,8) de juillet à novembre 2022. La séroprévalence des anticorps acquis par le vaccin était de 45,2 % de juillet à novembre 2022 (IC à 95% : 34,3–56,58). Aucune différence dans les facteurs sociodémographiques (âge, sexe, revenu ou appartenance ethnique) n’a été identifiée pour les anticorps acquis lors d’une infection; cependant, les enfants avec des anticorps acquis par le vaccin étaient plus susceptibles d’être plus âgés, d’avoir des mères ayant fait des études universitaires et d’avoir des mères également vaccinées.
Conclusion
Nos résultats fournissent une référence pour la séroprévalence des anticorps du SRAS-CoV-2 chez les enfants de Toronto. La surveillance continue du statut sérologique des enfants est importante, en particulier avec l’émergence de nouveaux variants préoccupants, la faible couverture vaccinale et l’arrêt des tests PCR.
Mots-clés: SRAS-CoV-2, Séroprévalence, Enfants, Soins primaires, Anticorps, Toronto, COVID-19, Vaccination
Introduction
Evaluating the seroprevalence of SARS-CoV-2 antibodies in children is important for assessing the burden of infection in this population, guiding public health interventions, and monitoring disease transmission dynamics.
While numerous studies have investigated the seroprevalence of SARS-CoV-2 antibodies in adults, data on paediatric populations remain limited. This leaves significant gaps in knowledge regarding the extent of viral exposure and the development of infection-acquired and vaccine-acquired immunity in children. While there have been several serological surveys conducted on children across the United States (Clarke, 2022), including in regions such as Texas (Messiah et al., 2023) and Arkansas (Boehme et al., 2022), many of these studies were carried out in the early stages of the pandemic, with no published results available for studies conducted beyond February 2022. Furthermore, although the results of serological surveys on children have been reported in Canadian regions such as British Columbia (Skowronski et al., 2022) and Quebec (Zinszer et al., 2021), there have been no published findings from serological surveys in Ontario. Additionally, there is a notable scarcity of serological survey reports in children under the age of 5 years, a particularly important demographic considering their ineligibility for COVID-19 vaccines until late July 2022. Addressing these gaps is imperative to inform evidence-based strategies aimed at protecting the health and well-being of children in the face of the ongoing pandemic.
Moreover, prevention measures have changed over time. Between January and July 2021, schools across the province were closed twice due to increasing case numbers, resulting in a total of 28 weeks of missed in-person learning (Herhalt, 2021). When in-person learning resumed in September 2021, masks were mandated for children in grades 1 and above until March 2022 (Jabakhanji & Knope, 2022). Vaccines became available for children aged 5 to 11 years in November 2021, and for children aged 6 months to less than 5 years in July 2022. Understanding the seroprevalence of COVID-19 antibodies over time is important to examine the impact of these preventive measures and to guide future public health strategies.
This study presents the findings of serological surveys from participants in the TARGet Kids! COVID-19 Study of Children in Families which was conducted in Toronto, Ontario, examining the seroprevalence of SARS-CoV-2 antibodies from January 2021 to November 2022. The objective was to examine the seroprevalence of both infection-acquired antibodies and vaccine-acquired antibodies as well as explore the relationships between seroprevalence and social determinants, including income, maternal education, and parental ethnicity.
Methods
Study design and conduct
A prospective cohort study was conducted in Toronto, Ontario. The study included healthy children and youth aged 0 to 16 years who were participating in the TARGet Kids! COVID-19 Study of Children and Families. TARGet Kids! is a primary care practice–based research network that recruits and prospectively follows children through primary healthcare system encounters, with additional questionnaires collected as part of the COVID-19 study (Carsley et al., 2019).
Starting in April 2020, TARGet Kids! followed participants through the TARGet Kids! COVID-19 Study of Children and Families to investigate changes in SARS-CoV-2 seroprevalence, health behaviours, physical health, and mental health throughout the pandemic. Children who had a visit with their primary care provider in the prior two years were contacted by email or phone call inviting them to participate in the study. Beginning in January 2021, children were invited to provide an at-home dried blood spot (DBS) sample at quarterly intervals. Recruitment to the study, including invitation to provide DBS, was ongoing throughout the study period.
At-home dried blood spot kits included detailed instructions for collection, storage, and mailing of the samples. Video conference appointments were also made available to guide participants through each step of the process. Parents used BD Microtainer lancets and a Whatman 903 protein saver card to collect their child’s dried blood spot samples. After drying the sample for a minimum of 2 hours, parents phoned the study team, who picked up the sample via courier to Mount Sinai Services Laboratories.
Dried blood spot (DBS) cards were stored at − 80 °C upon receipt at the lab. For analysis, two 3 mm punches were extracted from each card and eluted in 80 µl PBST plus 1% Triton X-100 (if there was only enough blood for one 3 mm punch, the sample was eluted in 40 µl). Participants’ serostatus was ascertained using a custom-developed research-based validated chemiluminescent enzyme-linked immunosorbent assay (ELISA) that used the full-length spike trimer, its receptor binding domain, and nucleocapsid as antigens as previously described. The ELISA assay was validated using positive control samples (convalescent patients with PCR‐confirmed COVID‐19) and negative control samples (samples acquired prior to November 2019 (pre‐COVID)) (Colwill et al., 2022). Total IgG was detected using anti-IgG#5-HRP at a 1:6700 dilution. Raw values were normalized to a recombinant antibody standard (VHH72-hFc1X7) to create a relative ratio. All reagents were supplied by the National Research Council of Canada. Parents were emailed their child’s serology result along with an explanation of what the result signified.
Ethical approval for this study was obtained from the Research Ethics Boards of the SickKids Research Institute, Unity Health Toronto, and the Toronto Academic Health Science Network (TAHSN).
Outcomes and covariates
The primary outcome was the seroprevalence of SARS-CoV-2 infection-acquired antibodies. The secondary outcome was the seroprevalence of SARS-CoV-2 vaccine-acquired antibodies. To distinguish between an infection- and vaccine-induced humoral immune response, we used a conceptual decision tree outlined by Duarte et al., described in detail elsewhere (Colwill et al., 2022; Duarte et al., 2022). Briefly, we used parent-reported child history of vaccination (‘Has your child received at least one dose of the COVID-19 vaccine?’) and tests for both anti-spike (S) and anti-nucleocapsid (N) antibodies. If an individual tested negative for anti-S antibodies, they were unlikely to have been infected or vaccinated and were classified as ‘no prior infection or vaccination’ (though it is possible that their antibody levels were below the detection limit of the test). For unvaccinated individuals who tested positive for anti-S antibodies, this indicated a likely previous infection and they were classified as such. For vaccinated individuals who tested positive for anti-S antibodies, we ascertained whether they had a prior infection based on anti-N seropositivity: those not seropositive for anti-N antibodies were classified as vaccinated with no previous infection, and those seropositive for anti-N antibodies were classified as vaccinated with a previous infection. Individuals were classified as ‘indeterminate’ if they were seropositive for anti-S, but had no further information on parent-reported vaccination status.
Sample collection was grouped into semi-annual periods (January to June 2021, July to December 2021, January to June 2022, July to November 2022). If participants returned multiple samples during a single period, they were classified as ‘positive’ if any sample was positive for SARS-CoV-2 antibodies, and negative if all returned samples were negative for SARS-CoV-2 antibodies.
To characterize the seroprevalence of SARS-CoV-2 antibodies by sociodemographic characteristics, we used pre-pandemic TARGet Kids! parent-reported data about child age, sex, maternal and paternal ethnicity, highest level of maternal education (‘What is the highest level of education completed by mother?’), before-tax household income (‘What was your total family income before taxes last year?’), and dwelling type (‘Do you live in a house or apartment?’). This was linked to information from the TARGet Kids! COVID-19 Study on family essential worker status (‘Is anybody in the household considered an essential worker?’), household density (‘How many people are currently in your household?’), and parent and child vaccination status (‘Have you or your child been vaccinated against COVID-19?’).
Statistical analysis
Descriptive statistics were calculated for all outcomes and covariates. To obtain 95% confidence intervals for the crude seroprevalence of infection-acquired antibodies or vaccine-acquired antibodies, or both, we used the binomial Wilson Score method (Agresti & Coull, 1998). The crude seroprevalence by each covariate and period was also calculated using the Wilson Score method. As an exploratory analysis, to determine the univariate association between each covariate and seroprevalence of SARS-CoV-2 antibodies while adjusting for period and accounting for repeated measures and rare outcomes, we used logistic generalized estimating equations (GEE) models with an exchangeable correlation structure and a Firth-type penalty term to account for small cell sizes. To determine adjusted associations between sociodemographic characteristics and seroprevalence of SARS-CoV-2 antibodies, we fit GEE models adjusting for age, child sex, family essential worker status (yes vs. no), maternal education (university-educated vs. less than university-educated), self-reported income, maternal European ethnicity (yes vs. no), paternal European ethnicity (yes vs. no), and period of DBS collection, with a Firth-type penalty term. All analyses were conducted using R v. 4.2.2 (R Core Team, 2022).
Results
A total of 475 unique participants provided 815 dried blood spot samples. Participation was highest from January to June 2021 (345 samples returned), with 181 returned from July to December 2021, 216 returned from January to June 2022, and 73 returned from July to November 2022. No clinically important differences were seen between participants in each of the sample collection periods, though children who submitted samples in the last period versus the first period were more likely to be from families with incomes of ≥ $150,000 (38.7% vs. 31.4%) and live in a house-type dwelling (90.3% vs. 83.4%) (Supplementary Table 1).
Participants providing a dried blood spot sample had a mean age of 6.39 years (SD = 3.17 years), and 227 (47.8%) of them were female (Table 1). The majority of children had mothers with at least a bachelor’s degree (358 (86.3%)), and 223 (32.9%) of mothers and 104 (27.8%) of fathers self-identified as members of racial or ethnic minorities. The majority of children lived in a house-type dwelling (327 (84.3%)) with a median household density of four members (IQR 3 to 4).
Table 1.
Demographics of TARGet Kids! children aged 0 to 16 years providing dried blood spots (DBS) by individual and household characteristics, January 2021 to November 2022 in Toronto, ON
| n | Overall |
|---|---|
| 475 | |
| Age in years (mean (SD)) | 6.39 (3.17) |
| Age group (%) | |
| 6 months–4 years | 174 (36.9) |
| 5–11 years | 281 (59.5) |
| ≥ 12 years | 17 (3.6) |
| Household density (mean (SD)) | 4.01 (0.88) |
| Female sex, n (%) | 227 (47.8) |
| Parent essential worker status, n (%) | 20 (4.2) |
| Maternal university education, n (%) | 358 (86.3) |
| Household income (%) | |
| < $50,000 | 16 (3.9) |
| $50,000 to $99,999 | 64 (15.6) |
| $100,000 to $149,999 | 192 (46.8) |
| ≥ $150,000 | 138 (33.7) |
| Childcare attendance, n (%) | 137 (71.7) |
| Maternal European ethnicity, n (%) | 251 (67.1) |
| Paternal European ethnicity, n (%) | 269 (71.9) |
| House-type dwelling, n (%) | 327 (84.3) |
| Parent vaccination status, n (%) | 287 (65.4) |
Seroprevalence of SARS-CoV-2 infection-acquired antibodies and vaccine-acquired antibodies
Over the course of the study, 103 unique participants had evidence of infection-acquired antibodies out of 475 children tested (22%). Crude seroprevalence of infection-acquired antibodies was 2.6% (95%CI 1.4 to 4.9) (9/342 children) from January to June 2021, 7.7% (95%CI 4.7 to 12.6) from July to December 2021, 43.1% (95%CI 36.6 to 49.7) from January to June 2022, and 50.7% (95%CI 39.5 to 61.8) (37/73 children) from July to November 2022 (Fig. 1a). Four indeterminate samples from four unique participants were collected from January to November 2022 and were classified as seronegative. If these samples were removed, the crude seroprevalence was 43.5% (95%CI 37.0 to 50.2) from January to June 2022 and 52.1% (95%CI 40.7 to 63.3) from July to November 2022.
Fig. 1.
Seroprevalence of a infection-acquired antibodies, b vaccine-acquired antibodies, c either infection- or vaccine-acquired antibodies among TARGET Kids! children aged 0–16 years in Toronto, Ontario
Seroprevalence of vaccine-acquired antibodies was 1.5% (95%CI 0.6 to 3.4) from January to June 2021, 8.8% (95%CI 4.4 to 13.9) from July to December 2021, 48.6% (95%CI 42.0 to 55.2) from January to June 2022, and 45.2% (95%CI 34.3 to 56.6) from July to November 2022 (Fig. 1b). By the last sample collection period (July to November 2022), 80.8% (95%CI 70.3 to 88.2) of children had evidence of either infection- or vaccine-acquired antibodies (Fig. 1c). Seroprevalence was comparable to parent-reported child vaccination status (January to June 2021, 0.58% (95%CI 0.16 to 2.1); July to December 2021, 8.3% (95%CI 0.51 to 13.2); January 2022 to June 2022, 48.1% (95%CI 41.6 to 54.8); July to November 2022, 43.8% (95%CI 33.0 to 55.2)).
Supplementary eFigure 1 shows evidence of both infection- and vaccine-acquired antibodies in children.
Determinants of SARS-CoV-2 infection-acquired antibodies
Table 2 shows crude seroprevalence and odds ratios for infection-acquired antibodies by age group, sex, family essential worker status, mother’s highest level of education, household income, childcare attendance, maternal ethnicity, paternal ethnicity, dwelling type, household density, and parent vaccination status. After adjusting for period of specimen collection, we did not find evidence of an association between any of these variables and seroprevalence of infection-acquired antibodies (Table 2). Multivariable analyses adjusting for pertinent sociodemographic characteristics and period also found no evidence of association between presence of infection-acquired antibodies and sex, age, essential worker status, education, income, and parental ethnicity (Table 3).
Table 2.
Crude seroprevalence and seroprevalence odds ratios of infection-acquired antibodies among TARGET Kids! children aged 0‒16 years in Toronto, Ontario by sociodemographic characteristics, January 2021 to November 2022
| Characteristic | Level | Crude seroprevalence (95%CI)a | Odds ratiob | |||
|---|---|---|---|---|---|---|
| January – June 2021 N = 342 |
July – December 2021 N = 181 |
January – June 2022 N = 216 |
July – November 2022 N = 73 |
|||
| Age group | 6 mo–4 yrs | 0.8 (0 to 4.4) | 11.9 (5.9 to 22.5) | 48.4 (36.6 to 60.4) | 60.9 (40.8 to 77.8) | Ref |
| 5–11 yrs | 3.8 (2 to 7.4) | 6.2 (3 to 12.2) | 42.1 (34.1 to 50.6) | 45.5 (31.7 to 59.9) | 0.80 (0.48 to 1.32) | |
| ≥ 12 yrs | 0 (0 to 32.4) | 0 (0 to 29.9) | 23.5 (9.6 to 47.3) | 50 (18.8 to 81.2) | 0.59 (0.22 to 1.59) | |
| Child sex | Male | 2.9 (1.2 to 6.5) | 4.2 (1.6 to 10.3) | 43.8 (34.7 to 53.4) | 52.6 (37.3 to 67.5) | Ref |
| Female | 2.4 (0.9 to 6) | 11.6 (6.4 to 20.1) | 42.3 (33.6 to 51.6) | 48.6 (33 to 64.4) | 0.97 (0.57 to 1.63) | |
| Parent essential worker status | No | 2.7 (1.4 to 5.1) | 7.7 (4.6 to 12.8) | 42.1 (35.6 to 48.9) | 52.1 (40.7 to 63.3) | Ref |
| Yes | 0 (0 to 22.8) | 7.7 (0.4 to 33.3) | 71.4 (35.9 to 91.8) | 0 (0 to 65.8) | 1.41 (0.44 to 4.55) | |
| Maternal education | Less than university | 0 (0 to 8.2) | 16 (6.4 to 34.7) | 58.8 (42.2 to 73.6) | 63.6 (35.4 to 84.8) | Ref |
| University or greater | 3.3 (1.8 to 6.2) | 7.3 (4 to 12.9) | 40.4 (32.9 to 48.4) | 47.1 (34.1 to 60.5) | 0.51 (0.25 to 1.07) | |
| Household income | < $50,000 | 0 (0 to 29.9) | 37.5 (13.7 to 69.4) | 66.7 (35.4 to 87.9) | 100 (43.9 to 100) | Ref |
| $50,000 to $99,999 | 3.9 (1.1 to 13.2) | 3.8 (0.2 to 18.9) | 38.9 (24.8 to 55.1) | 30.8 (12.7 to 57.6) | 0.39 (0.09 to 1.61) | |
| $100,000 to $149,999 | 3.3 (1.4 to 7.5) | 6.7 (2.9 to 14.7) | 40.3 (30 to 51.4) | 50 (30.7 to 69.3) | 0.38 (1.00 to 1.41) | |
| ≥ $150,000 | 2.1 (0.6 to 7.2) | 7.5 (3 to 17.9) | 47.6 (35.8 to 59.7) | 54.2 (35.1 to 72.1) | 0.51 (0.14 to 1.91) | |
| Childcare attendance | No | 5.1 (1.4 to 16.9) | 0 (0 to 12.5) | 41.9 (26.4 to 59.2) | 40 (16.8 to 68.7) | Ref |
| Yes | 1.8 (0.5 to 6.4) | 6.2 (2.1 to 16.8) | 45.9 (34 to 58.3) | 65 (43.3 to 81.9) | 1.49 (0.62 to 3.61) | |
| Maternal European ethnicity | 0 | 4.3 (1.7 to 10.5) | 10 (4.3 to 21.4) | 46.7 (34.6 to 59.1) | 65 (43.3 to 81.9) | Ref |
| 1 | 2.5 (1.1 to 5.8) | 6.3 (2.9 to 13.1) | 41.3 (32.5 to 50.7) | 40 (25.6 to 56.4) | 0.73 (0.40 to 1.33) | |
| Paternal European ethnicity | 0 | 4.8 (1.9 to 11.7) | 12.2 (5.3 to 25.5) | 44.4 (30.9 to 58.8) | 56.2 (33.2 to 76.9) | Ref |
| 1 | 1.9 (0.8 to 4.9) | 5.8 (2.7 to 12.1) | 41.7 (33.2 to 50.6) | 44.7 (30.1 to 60.3) | 0.97 (0.49 to 1.89) | |
| Dwelling type | Apartment | 0 (0 to 7.3) | 14.3 (4 to 39.9) | 48.3 (31.4 to 65.6) | 66.7 (30 to 90.3) | Ref |
| House | 3.7 (1.9 to 6.8) | 8.7 (5 to 14.6) | 44.9 (37.1 to 53) | 48.2 (35.7 to 61) | 0.72 (0.34 to 1.54) | |
| Household density | 2 | 0 (0 to 24.2) | 0 (0 to 43.4) | 0 (0 to 56.1) | 50 (15 to 85) | Ref |
| 3 | 2.4 (0.7 to 8.4) | 6.7 (1.8 to 21.3) | 39.5 (26.4 to 54.4) | 46.7 (24.8 to 69.9) | 1.86 (0.29 to 11.82) | |
| 4 | 3.1 (1.3 to 7.1) | 4.9 (2.1 to 11) | 40.9 (32.3 to 50) | 46.9 (30.9 to 63.6) | 1.86 (0.31 to 11.14) | |
| ≥ 5 | 2.8 (0.8 to 9.6) | 14.6 (6.9 to 28.4) | 51.9 (38.9 to 64.6) | 57.9 (36.3 to 76.9) | 2.68 (0.43 to 16.73) | |
| Parent vaccination status | 0 | 0.7 (0 to 4.1) | 11.1 (3.9 to 28.1) | 66.7 (45.4 to 82.8) | 80 (54.8 to 93) | Ref |
| 1 | 4.5 (2.3 to 8.7) | 6.1 (3.2 to 11.2) | 40.6 (33.9 to 47.7) | 42.9 (30.8 to 55.9) | 0.63 (0.32 to 1.25) | |
a 95%CI obtained using the Wilson Score method
b Odds ratios adjusting for period of specimen collection
Table 3.
Adjusted odds ratios by age, sex, family essential worker status, maternal education, household income, and parental ethnicity from generalized estimating equations, January 2021 to November 2022 among TARGET Kids! children aged 0‒16 years in Toronto, ON
| Infection-acquired antibodies Adjusted OR (95%CI) |
Vaccination-acquired antibodies Adjusted OR (95%CI) |
|
|---|---|---|
| Age in years, per year increase | 0.97 (0.88 to 1.06) | 1.46 (1.27 to 1.66) |
| Female child sex vs. male | 1.07 (0.57 to 1.99) | 1.15 (0.60 to 2.18) |
| Parent essential worker vs. non-essential worker | 1.64 (0.45 to 5.93) | 1.22 (0.18 to 8.38) |
| Maternal university education vs. less than university education | 0.56 (0.23 to 1.33) | 3.01 (1.13 to 8.01) |
| Household income | ||
| $50,000 to $99,999 vs. < $50,000 | 0.46 (0.10 to 2.07) | 3.67 (0.84 to 16.04) |
| $100,000 to $149,999 vs. < $50,000 | 0.60 (0.15 to 2.50) | 2.62 (0.57 to 12.07) |
| ≥ $150,000 vs. < $50,000 | 0.80 (0.20 to 3.27) | 4.33 (0.93 to 20.11) |
| Maternal European ethnicity vs. non-European ethnicity | 0.75 (0.38 to 1.49) | 0.69 (0.33 to 1.43) |
| Paternal European ethnicity vs. non-European ethnicity | 1.12 (0.53 to 2.37) | 1.64 (0.72 to 3.75) |
Determinants of SARS-CoV-2 vaccine-acquired antibodies
Table 4 demonstrates crude seroprevalence and odds ratios for vaccine-acquired antibodies by sociodemographic characteristics. After adjusting for period of specimen collection, we found that compared to children from households making less than $50,000 per year, higher before-tax annual household income was associated with a higher odds of vaccine-acquired antibodies (Table 4).
Table 4.
Crude seroprevalence and seroprevalence odds ratios of vaccine-acquired antibodies among TARGET Kids! children aged 0‒16 years in Toronto, Ontario by sociodemographic characteristics, January 2021 to November 2022
| Characteristic | Level | Crude seroprevalence (95% CI)a | Odds ratiob | |||
|---|---|---|---|---|---|---|
| January – June 2021 N = 342 |
July – December 2021 N = 181 |
January – June 2022 N = 216 |
July – November 2022 N = 73 |
|||
| Age group | 6 mo–4 yrs | 0 (0 to 3) | 0 (0 to 6.1) | 3.1 (0.9 to 10.7) | 4.3 (0.2 to 21) | Ref |
| 5–11 yrs | 2.4 (1 to 5.5) | 9.7 (5.5 to 16.6) | 65.4 (57 to 73) | 59.1 (44.4 to 72.3) | 39.2 (10.0 to 153.3) | |
| ≥ 12 yrs | 0 (0 to 32.4) | 55.6 (26.7 to 81.1) | 94.1 (73 to 99.7) | 100 (61 to 100) | 440 (82.2 to 2357.84) | |
| Child sex | Male | 1.7 (0.6 to 4.9) | 8.4 (4.3 to 15.7) | 47.6 (38.3 to 57.1) | 50 (34.8 to 65.2) | Ref |
| Female | 1.2 (0.3 to 4.2) | 9.3 (4.8 to 17.3) | 49.5 (40.4 to 58.7) | 40 (25.6 to 56.4) | 1.20 (0.69 to 2.10) | |
| Parent essential worker status | No | 1.5 (0.7 to 3.5) | 8.3 (5 to 13.5) | 49.8 (43 to 56.5) | 45.1 (34 to 56.6) | Ref |
| Yes | 0 (0 to 22.8) | 15.4 (4.3 to 42.2) | 14.3 (0.7 to 51.3) | 50 (2.6 to 97.4) | 0.67 (0.15 to 3.01) | |
| Maternal education | Less than university | 0 (0 to 8.2) | 4 (0.2 to 19.5) | 38.2 (23.9 to 55) | 9.1 (0.5 to 37.7) | Ref |
| University | 1.9 (0.8 to 4.3) | 10.9 (6.7 to 17.3) | 57 (49 to 64.6) | 58.8 (45.2 to 71.2) | 2.36 (0.79 to 6.99) | |
| Household income | < $50,000 | 0 (0 to 29.9) | 0 (0 to 32.4) | 0 (0 to 29.9) | 0 (0 to 56.1) | Ref |
| $50,000 to $99,999 | 3.9 (1.1 to 13.2) | 11.5 (4 to 29) | 58.3 (42.2 to 72.9) | 30.8 (12.7 to 57.6) | 21.1 (6.86 to 65.0) | |
| $100,000 to $149,999 | 1.3 (0.4 to 4.7) | 9.3 (4.6 to 18) | 46.8 (36 to 57.8) | 50 (30.7 to 69.3) | 17.2 (6.28 to 46.8) | |
| ≥ $150,000 | 1 (0.1 to 5.6) | 11.3 (5.3 to 22.6) | 66.7 (54.4 to 77.1) | 66.7 (46.7 to 82) | 32.3 (11.9 to 88.2) | |
| Childcare attendance | No | 5.1 (1.4 to 16.9) | 14.8 (5.9 to 32.5) | 67.7 (50.1 to 81.4) | 60 (31.3 to 83.2) | Ref |
| Yes | 0 (0 to 3.4) | 8.3 (3.3 to 19.6) | 77 (65.1 to 85.8) | 75 (53.1 to 88.8) | 1.08 (0.44 to 2.65) | |
| Maternal European ethnicity | No | 4.3 (1.7 to 10.5) | 4 (1.1 to 13.5) | 55 (42.5 to 66.9) | 40 (21.9 to 61.3) | Ref |
| Yes | 0.5 (0 to 2.8) | 12.6 (7.4 to 20.8) | 52.3 (43 to 61.4) | 51.4 (35.6 to 67) | 1.10 (0.58 to 2.10) | |
| Paternal European ethnicity | No | 4.8 (1.9 to 11.7) | 4.9 (1.3 to 16.1) | 48.9 (35 to 63) | 43.8 (23.1 to 66.8) | Ref |
| Yes | 0.5 (0 to 2.7) | 10.7 (6.1 to 18.1) | 55.8 (46.9 to 64.4) | 44.7 (30.1 to 60.3) | 1.27 (0.62 to 2.56) | |
| Dwelling type | Apartment | 0 (0 to 7.3) | 0 (0 to 21.5) | 55.2 (37.5 to 71.6) | 50 (18.8 to 81.2) | Ref |
| House | 2 (0.9 to 4.7) | 10.9 (6.7 to 17.2) | 53.7 (45.7 to 61.6) | 50 (37.3 to 62.7) | 1.04 (0.46 to 2.35) | |
| Household density | 2 | 0 (0 to 24.2) | 0 (0 to 43.4) | 33.3 (1.7 to 79.2) | 50 (15 to 85) | Ref |
| 3 | 1.2 (0.1 to 6.5) | 10 (3.5 to 25.6) | 37.2 (24.4 to 52.1) | 46.7 (24.8 to 69.9) | 1.09 (0.16 to 10.39) | |
| 4 | 1.9 (0.6 to 5.3) | 4.9 (2.1 to 11) | 53 (44 to 61.9) | 46.9 (30.9 to 63.6) | 1.27 (0.21 to 11.49) | |
| 5 | 1.4 (0.1 to 7.5) | 19.5 (10.2 to 34) | 50 (37.1 to 62.9) | 47.4 (27.3 to 68.3) | 1.59 (0.17 to 14.96) | |
| Parent vaccination status | No | 0 (0 to 2.8) | 0 (0 to 12.5) | 0 (0 to 15.5) | 0 (0 to 20.4) | Ref |
| Yes | 2.8 (1.2 to 6.4) | 10.8 (6.8 to 16.8) | 54.7 (47.6 to 61.6) | 58.9 (45.9 to 70.8) | 98.2 (54.4 to 177.3) | |
a 95%CI obtained using the Wilson Score method
b Odds ratios adjusting for period of specimen collection
In analyses adjusting only for period of specimen collection, age (age ≥ 12 vs < 5 years: OR = 39.2 (95%CI 10.0 to 153); age 5 to 11 vs. < 5 years: OR = 440 (95%CI 82 to 2357) and maternal vaccination status (vaccinated vs. unvaccinated, OR = 98.2 (95%CI 54.4 to 177.3)) and income (vs. < $50,000: $50,000 to $99,999, OR = 21.1 (95%CI 6.86 to 65.0); $100,000 to $149,999, OR = 17.2 (95%CI 6.28 to 46.8); ≥ $150,000, OR = 32.3 (95%CI 11.9 to 88.2)) were associated with seroprevalence of vaccine-acquired antibodies. After adjustment for sex, age, essential worker status, education income, maternal European ethnicity, paternal European ethnicity, and sample collection period, we found evidence that children with mothers with university education (compared to less than university education) was associated with higher seroprevalence of vaccine-acquired antibodies (aOR = 3.01, 95%CI 1.13 to 8.01), and family income was no longer associated with seroprevalence of vaccine-acquired antibodies (Table 4). Evidence of an association still persisted for child’s age (per year increase, OR = 1.46 (95%CI 1.27 to 1.66)) and maternal education after adjusting for other sociodemographic factors.
Discussion
The crude seroprevalence for SARS-CoV-2 infection-acquired antibodies showed an increase from the first half of 2021 to the second half of 2022. By the latter half of 2022, roughly half the children in our sample demonstrated evidence of SARS-CoV-2 infection-acquired antibodies, and half the children also demonstrated evidence of SARS-CoV-2 vaccine-acquired antibodies. No differences in sociodemographic factors (age, sex, income, or ethnicity) were identified for infection-acquired antibodies. However, children who were seropositive for vaccine-acquired antibodies tended to be older, with mothers with a university education, and with mothers who had also been vaccinated.
Our findings suggest a high level of exposure to the virus among children during the study period, which is consistent with the widespread transmission of the virus observed in the general population. From December 2021 to February 2022, a nationwide study found that overall US seroprevalence increased from 34% (95%CI 33.1 to 34.0) to 58% (95%CI 57 to 58). Over the same period, seroprevalence increased from 44% (95%CI 43 to 46) to 75% (95%CI 74 to 77) among children aged 0–11 years (Clarke, 2022). Potential geographic and public health strategy differences (e.g. population density, transmission containment strategies) may explain the comparatively lower seroprevalence in our sample.
Seroprevalence of infection-acquired antibodies was comparable to those of the EnCORE study in Montreal, which examined children aged 2 to 17 years and found a crude seroprevalence of 9.9% from May to July 2021, and which rose to 58.1% by May to September 2022 (Results, n.d.; Zinszer et al., 2021). Similarly, a repeated cross-sectional study of children conducted in British Columbia found that the seroprevalence of infection-acquired antibodies was 61% by July–August 2022 (Skowronski et al., 2022).
Our study observed an increase in the crude seroprevalence of SARS-CoV-2 infection-acquired antibodies from the first half of 2021 to the latter half of 2022. In terms of sociodemographic factors, we found no evidence of differences in age, sex, income, or ethnicity among children who were seropositive for infection-acquired antibodies. This is consistent with other studies finding no significant association between risk of seropositivity and social determinants such as age, sex, and parental education (Richard et al., 2022; Waterfield et al., 2021; McKinnon et al., 2021; Zinszer et al., 2021). This underscores the indiscriminate nature of the virus and the importance of implementing preventive measures across all segments of the population.
However, we observed some differences among children who were seropositive for vaccine-acquired antibodies. These children tended to be older, have mothers with a university education, and have mothers who had also been vaccinated, consistent with other studies. These data are consistent with provincially reported vaccination data that suggested vaccine coverage estimates of 81% among 12‒17-year-olds, 49% among 5‒11-year-olds, and 7% among children under 5 years old by the end of November 2022. Moreover, our results suggest higher vaccine coverage among families with higher educational attainment, possibly due to a greater awareness of the benefits of vaccination and trust in the healthcare system. Our results also indicate that parental vaccination status may influence the decision to vaccinate their children, highlighting the role of parental attitudes and behaviours in children’s health outcomes (Hetherington et al., 2020; Troiano & Nardi, 2021).
Our study is subject to several limitations. First, our sample may reflect children from families who have greater health-seeking behaviours than other families, as they access primary care and consent to take part in research. These families may be more likely to participate in interventions to prevent SARS-CoV-2 infection, such as wearing masks, social distancing, and vaccination. However, the proportion of children with vaccine-acquired antibodies in our sample is comparable to vaccine coverage estimates recorded by provincial systems. Second, our study faced attrition, particularly toward the end of the study; however, characteristics between each sample collection period remained similar between groups (see Supplementary Table 1). In addition, since the anti-spike assay has higher sensitivity than the anti-nucleocapsid assay (Colwill et al., 2022) and vaccinated individuals have a lower seroconversion rate than unvaccinated individuals for nucleocapsid (Follmann et al., 2022), we are likely undercounting infections in vaccinated individuals. Moreover, the potential decrease in antibody titers over time may impact the interpretation of results, as lower antibody levels may lead to an underestimation of seroprevalence. Finally, statistical power was not sufficient to adjust for an extensive list of sociodemographic characteristics in our study, and our study may also be vulnerable to type II error.
Conclusion
Our findings provide valuable insights into the seroprevalence of SARS-CoV-2 infection-acquired and vaccine-acquired antibodies among children. The findings from this study establish a reference point for the seroprevalence of SARS-CoV-2 antibodies in children accessing primary care in Toronto, Ontario. Ongoing serological monitoring is important given the emergence of new variants of concern, low levels of vaccination among young children, and limited RT-PCR testing in this age group. Continued serological monitoring helps to inform public health strategies and interventions aimed at protecting this vulnerable population.
Contributions to knowledge
What does this study add to existing knowledge?
This study adds to existing knowledge by providing insights into the seroprevalence of SARS-CoV-2 infection-acquired and vaccine-acquired antibodies in a cohort of children receiving primary care in Toronto, Canada.
The study reveals changing seroprevalence rates over time, allowing for a better understanding of the dynamics of COVID-19 antibodies in this population.
Additionally, it identifies sociodemographic factors associated with vaccine-acquired antibodies, contributing to the understanding of vaccination trends among children.
What are the key implications for public health interventions, practice, or policy?
Increasing seroprevalence rates highlight the evolving nature of the pandemic in the studied population.
The identification of factors associated with vaccine-acquired antibodies emphasizes the importance of targeted vaccination campaigns, especially among younger children and among children with mothers who are unvaccinated and who have less than university education.
The study underscores the necessity of ongoing serological monitoring, particularly considering concerns about new variants, low vaccine coverage, and changes in testing protocols.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
We thank all of the participating families for their time and involvement in TARGet Kids! and are grateful to all practitioners who are currently involved in the TARGet Kids! practice-based research network. We also thank the TARGet Kids! PACT for their generous contribution of time and participation in child health research.
Members of the TARGet Kids! Collaboration:
Co-Leads: Catherine S. Birken, MD, and Jonathon L. Maguire, MD.
Executive Committee: Christopher Allen, BSc; Laura N. Anderson, PhD; Dana Arafeh, MHI;
Mateenah Jaleel, BSc; Charles Keown-Stoneman, PhD; Natricha Levy McFarlane, MPhil; and Jessica A. Omand RD, PhD.
Investigators and Trainees: Mary Aglipay, MSc; Imaan Bayoumi, MD MSc; Cornelia M. Borkhoff, PhD; Sarah Carsley, PhD; Katherine Cost, PhD; Curtis D’Hollander, RD MSc; Anne Fuller, MD; Laura Kinlin, MD MPH; Patricia Li, MD MSc; Pat Parkin, MD; Nav Persaud, MD MSc; Izabela Socynska, RD MSc; Shelley Vanderhout, RD PhD; Leigh Vanderloo, PhD; and Peter Wong, MD PhD.
Research Staff: Xuedi Li, MSc; Michelle Mitchell, BA; Hakimat Shaibu, MSc; and Yulika Yoshida-Montezuma, MPH.
Clinical Site Research Staff: Marivic Bustos, RPN; Pamela Ruth Flores, MD; Martin Ogwuru, MBBS; Sharon Thadani, MLT; Julia Thompson, SSRP; Laurie Thompson, MLT; Kardelen Kurt, BSc; and Ataat Malick, MD.
Parent Partners: Jennifer Batten; Jennifer Chan; John Clark; Maureen Colford; Amy Craig; Kim De Castris-Garcia; Sharon Dharman; Anthony Garcia; Sarah Kelleher; Sandra Marquez; Salimah Nasser; Tammara Pabon; Michelle Rhodes; Rafael Salsa; Jia Shin; Julie Skelding; Daniel Stern; Kerry Stewart; Erika Sendra Tavares; Shannon Weir; and Maria Zaccaria.
Offord Centre for Child Studies Collaboration: Principal Investigator: Magdalena Janus, PhD; Co-investigator: Eric Duku, PhD; Research Team: Caroline Reid-Westoby, PhD; Patricia Raso, MSc; and Amanda Offord, MSc.
Site Investigators: Emy Abraham, MD; Sara Ali, MD; Kelly Anderson, MD; Gordon Arbess, MD; Jillian Baker, MD; Tony Barozzino, MD; Sylvie Bergeron, MD; Gary Bloch, MD; Joey Bonifacio, MD; Ashna Bowry, MD; Caroline Calpin, MD; Douglas Campbell, MD; Sohail Cheema, MD; Elaine Cheng, MD; Brian Chisamore, MD; Evelyn Constantin, MD; Karoon Danayan, MD; Paul Das, MD; Viveka De Guerra, MD; Mary Beth Derocher, MD; Anh Do, MD; Kathleen Doukas, MD; Anne Egger, BScN; Allison Farber, MD; Amy Freedman, MD; Sloane Freeman, MD; Sharon Gazeley, MD; Karen Grewal, MD; Charlie Guiang, MD; Dan Ha, MD; Curtis Handford, MD; Laura Hanson, BScN, RN; Leah Harrington, MD; Sheila Jacobson, MD; Lukasz Jagiello, MD; Gwen Jansz, MD; Paul Kadar, MD; Lukas Keiswetter, MD; Tara Kiran, MD; Holly Knowles, MD; Bruce Kwok, MD; Piya Lahiry, MD; Sheila Lakhoo, MD; Margarita Lam-Antoniades, MD; Eddy Lau, MD; Denis Leduc, MD; Fok-Han Leung, MD; Alan Li, MD; Patricia Li, MD; Roy Male, MD; Aleks Meret, MD; Elise Mok, MD; Rosemary Moodie, MD; Katherine Nash, BScN, RN; James Owen, MD; Michael Peer, MD; Marty Perlmutar, MD; Navindra Persaud, MD; Andrew Pinto, MD; Michelle Porepa, MD; Vikky Qi, MD; Noor Ramji, MD; Danyaal Raza, MD; Katherine Rouleau, MD; Caroline Ruderman, MD; Janet Saunderson, MD; Vanna Schiralli, MD; Michael Sgro, MD; Hafiz Shuja, MD; Farah Siam, MD; Susan Shepherd, MD; Cinntha Srikanthan, MD; Carolyn Taylor, MD; Stephen Treherne, MD; Suzanne Turner, MD; Fatima Uddin, MD; Meta van den Heuvel, MD; Thea Weisdorf, MD; Peter Wong, MD; John Yaremko, MD; Ethel Ying, MD; Elizabeth Young, MD; and Michael Zajdman, MD.
Applied Health Research Centre: Peter Juni, MD; Gurpreet Lakhanpal, MSc; Gerald Lebovic, PhD; Audra Stitt, MSc; Kevin Thorpe, MMath; Ifeayinchukwu (Shawn) Nnorom, BSc; and Esmot ara Begum, PhD.
Mount Sinai Services Laboratory: Rita Kandel, MD; Michelle Rodrigues, PhD; Andrea Djolovic; Raya Assan; and Homa Bondar.
From Gingras lab:
We acknowledge Geneviève Mailhot, Melanie Delgado-Brand, Tulunay Tursun, and Freda Qi for their role in COVID-19 serology analysis. Antigens, protein standards, and secondary antibodies for ELISA were kindly provided by The Pandemic Response Challenge Program of the National Research Council of Canada (Dr. Yves Durocher); positive and negative control samples for ELISA assay calibration were from the National Microbiology Laboratory, Public Health Agency of Canada (Dr. John Kim). The robotics equipment used is housed in the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, a facility supported by the Canada Foundation for Innovation, the Ontario Government, and Genome Canada and Ontario Genomics (OGI-139). Anne-Claude Gingras leads the Functional Genomics and Structure–Function Pillar of CoVaRR-Net and is the Canada Research Chair (Tier 1) in Functional proteomics.
Author contributions
MA and JM developed the research question and designed the study. MA and CKS had full access to all data and take responsibility for the integrity of the data. MA led the statistical analysis and synthesis of results. MA drafted the manuscript. All authors contributed to the interpretation of results, editing, and critical review of the final manuscript, and approved the final version.
Funding
This study was supported by funding from the Canadian Institutes of Health Research (Grant 468613) and the COVID-19 Immunity Task Force, a Province of Ontario initiative to support Ontario’s ongoing response to COVID-19 and its related impacts.
Availability of data and material
All material and data used for this paper are available upon reasonable request to the corresponding author.
Code availability
Code can be made available upon request from the corresponding author.
Declarations
Conflict of interest
The authors declare no competing interests.
Ethics approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional (REB# 20–080 Unity Health Toronto Research Ethics) and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Jonathon Maguire, Email: jonathon.maguire@utoronto.ca.
on behalf of the TARGet Kids! Collaboration:
Christopher Allen, Laura N. Anderson, Dana Arafeh, Mateenah Jaleel, Natricha Levy McFarlane, Jessica A. Omand, Imaan Bayoumi, Cornelia M. Borkhoff, Sarah Carsley, Katherine Cost, Curtis D’Hollander, Anne Fuller, Laura Kinlin, Patricia Li, Pat Parkin, Nav Persaud, Izabela Socynska, Shelley Vanderhout, Leigh Vanderloo, Peter Wong, Xuedi Li, Michelle Mitchell, Hakimat Shaibu, Yulika Yoshida-Montezuma, Marivic Bustos, Pamela Ruth Flores, Martin Ogwuru, Sharon Thadani, Julia Thompson, Laurie Thompson, Kardelen Kurt, Ataat Malick, Jennifer Batten, Jennifer Chan, John Clark, Maureen Colford, Amy Craig, Kim De Castris-Garcia, Sharon Dharman, Anthony Garcia, Sarah Kelleher, Sandra Marquez, Salimah Nasser, Tammara Pabon, Michelle Rhodes, Rafael Salsa, Jia Shin, Julie Skelding, Daniel Stern, Kerry Stewart, Erika Sendra Tavares, Shannon Weir, Maria Zaccaria, Magdalena Janus, Eric Duku, Caroline Reid-Westoby, Patricia Raso, Amanda Offord, Emy Abraham, Sara Ali, Kelly Anderson, Gordon Arbess, Jillian Baker, Tony Barozzino, Sylvie Bergeron, Gary Bloch, Joey Bonifacio, Ashna Bowry, Caroline Calpin, Douglas Campbell, Sohail Cheema, Elaine Cheng, Brian Chisamore, Evelyn Constantin, Karoon Danayan, Paul Das, Viveka De Guerra, Mary Beth Derocher, Anh Do, Kathleen Doukas, Anne Egger, Allison Farber, Amy Freedman, Sloane Freeman, Sharon Gazeley, Karen Grewal, Charlie Guiang, Dan Ha, Curtis Handford, Laura Hanson, Leah Harrington, Sheila Jacobson, Lukasz Jagiello, Gwen Jansz, Paul Kadar, Lukas Keiswetter, Tara Kiran, Holly Knowles, Bruce Kwok, Piya Lahiry, Sheila Lakhoo, Margarita Lam-Antoniades, Eddy Lau, Denis Leduc, Fok-Han Leung, Alan Li, Patricia Li, Roy Male, Aleks Meret, Elise Mok, Rosemary Moodie, Katherine Nash, James Owen, Michael Peer, Marty Perlmutar, Navindra Persaud, Andrew Pinto, Michelle Porepa, Vikky Qi, Noor Ramji, Danyaal Raza, Katherine Rouleau, Caroline Ruderman, Janet Saunderson, Vanna Schiralli, Michael Sgro, Hafiz Shuja, Farah Siam, Susan Shepherd, Cinntha Srikanthan, Carolyn Taylor, Stephen Treherne, Suzanne Turner, Fatima Uddin, Meta van den Heuvel, Thea Weisdorf, Peter Wong, John Yaremko, Ethel Ying, Elizabeth Young, Michael Zajdman, Peter Juni, Gurpreet Lakhanpal, Gerald Lebovic, Audra Stitt, Kevin Thorpe, Ifeayinchukwu (Shawn) Nnorom, Esmot ara Begum, Rita Kandel, Michelle Rodrigues, Andrea Djolovic, Raya Assan, Homa Bondar, Geneviève Mailhot, Melanie Delgado-Brand, Tulunay Tursun, Freda Qi, Yves Durocher, John Kim, and Anne-Claude Gingras
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All material and data used for this paper are available upon reasonable request to the corresponding author.
Code can be made available upon request from the corresponding author.