Seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and adolescents in Montreal, Canada

Importance Repeated serological testing for SARS-CoV-2 allows the monitoring of antibody dynamics in populations, including detecting infections that are missed by RT-PCR or antigen testing. Understanding the factors associated with seroconversion and seroreversion as well as the duration of infection-induced antibodies can also inform public health recommendations regarding disease prevention and mitigation efforts. Objective To use serological testing to assess the prevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. Design This analysis reports on three rounds of data collection from a prospective cohort study (Enfants et COVID-19: Étude de séroprévalence [EnCORE]). The study rounds occurred as follows: Round 1 October 2020-March 2021, Round 2 May to July 2021, and Round 3 November 2021 to January 2022. Most Round 3 samples were collected prior to the spread of the Omicron BA.1 variant in Quebec. Setting Population-based sample. Participants Children and adolescents aged 2 to 17 years in Montreal, Canada. Exposure Potential exposure to SARS-CoV-2. Main Outcomes and Measures Participants provided dried blood spots (DBS) for antibody detection and parents completed online questionnaires for sociodemographics and COVID-19 symptoms and testing history. The serostatus of participants was determined by enzyme-linked immunosorbent assays (ELISAs) using the receptor-binding domain (RBD) from the spike protein and the nucleocapsid protein (N) as antigens. We estimated seroprevalence for each round of data collection and by participant and household characteristics. Seroconversion rates were calculated as were the likelihoods of remaining seropositive at six months and one year. Results The study included DBS samples from 1 632, 936, and 723 participants in the first, second, and third rounds of data collection, respectively. The baseline seroprevalence was 5·8% (95% CI 4·8-7·1), which increased to 10·5% and 10·9% for the respective follow-ups (95% CI 8·6-12·7; 95% CI 8·8-13·5). The overall average crude rate of seroconversion over the study period was 12·7 per 100 person-years (95% CI 10·9-14·5). Adjusted hazard rates of seroconversion by child and household characteristics showed higher rates in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. The likelihood of remaining seropositive at six months was 67% (95% CI 59-76) and dropped to 19% (95% CI 11%-33%) at one year. Conclusions and Relevance The data reported here provide estimates of pre-Omicron seroprevalence, seroconversion rates and time to seroreversion in a population-based cohort of children and adolescents. Serological studies continue to provide valuable contributions for infection prevalence estimates and help us better understand the dynamics of antibody levels following infection. Continued study of seroconversion and seroreversion can inform public health recommendations such as COVID-19 vaccination and booster schedules. Question What was the rate of seroconversion and time to seroreversion for SARS-CoV-2 antibodies among children and adolescents in Montreal between October 2020 to January 2022? Findings The overall average crude rate of seroconversion was 12·7 per 100 person-years (95% CI 10·9-14·5). We observed higher rates of seroconversion in children who were female, whose parent identified as a racial or ethnic minority, and in households with incomes less than 100K. Among all children who seroconverted, 71% had not been previously diagnosed with COVID-19. Median time to seroreversion was 7·5 months. Meaning Even before the emergence of the Omicron variants, we observed a high rate of seroconversion for infection-induced SARS-CoV-2 antibodies along with widespread antibody waning by one year. Many children and adolescents seroconverted despite not receiving a prior COVID-19 diagnosis, indicating that RT-PCR and antigen testing continue to underestimate true disease prevalence. ### Competing Interest Statement JP reports grants from MedImmune, grants and personal fees from Merck and AbbVie, and personal fees from AstraZeneca, all outside the submitted work. All other authors declare no conflicts of interest. ### Funding Statement Funding for this study was provided by the Public Health Agency of Canada through the COVID-19 Immunity Task Force to Dr Zinszer. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for preprint. ### 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: Comité d'éthique de la recherche en sciences et en santé (CERSES) of the Université de Montréal 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Individual participant data (after deidentification) and study documents will be available at study end. Researchers who wish to access the data should contact the corresponding author with a concise proposal for consideration. Researchers will be required to sign a data-access agreement.