Factors associated with severe acute respiratory syndrome-related coronavirus 2 infection in unvaccinated children and young adults

BACKGROUND Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults <25 years between November 2020-May 2021 and phase 2 enrolled children <10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSION SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms. ### Competing Interest Statement MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. SG has received research support and/or consulting fees from GlaxoSmithKline, Merck, Moderna, Pfizer, VBI Vaccines, Curevo Vaccine and Altona Diagnostics. BA received honoraria for participation in live meetings from Sanofi Pasteur France and Canada related to pertussis and RSV. Other authors have no conflicts of interest to disclose. ### Funding Statement This study was funded by grants from Michael Smith Health Research BC and the Public Health Agency of Canada. This work was supported by the BC Childrens Hospital Foundation to MS via salary awards, Michael Smith Health Research BC to MS via salary awards and to BA, and the Canadian Immunization Research Network Doctoral Award to BM via salary awards. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the University of British Columbia Childrens and Womens Research Ethics Board gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors * Anti-S : anti-spike BC : British Columbia BCCDC : BC Centre for Disease Control CI : confidence intervals COVID-19 : Coronavirus disease 2019 DBS : Dried blood spot GMC : geometric mean concentration IgG : immunoglobulin G MSD : Meso Scale Discovery PCR : polymerase chain reaction SARS-CoV-2 : severe acute respiratory syndrome coronavirus 2 SES : socioeconomic status STROBE : Strengthening the reporting of observational studies in epidemiology