Clinical trial NCT04448717: COVID-19: Longitudinal Study of Seroprevalence of SARS-CoV-2 Antibodies and Development of Immunity in School Children
Official title: Seroprevalence of SARS-CoV-2 Antibodies and Development of Immunity in a Public School Population - a Population-based Observational Study to Inform Policy Making
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SARS-CoV 2
COVID-19
Keywords: Seroprevalence
Seroepidemiology
School children
Switzerland
Schools
Households
Students
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Swiss School of Public Health (SSPH+)
First posted: 2020-06-26
Enrollment: 4250
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: School children, attending grades 1 to 9 in a public or private school in the Canton of Zurich, Switzerland.

Parents of participating children. School personnel of participating schools.

Brief summary: There is a lack of knowledge about how many children are infected with SARS-CoV-2, how often they are asymptomatic, and how long the immunity persists.

The main purpose of this study is to measure antibodies to SARS-CoV-2, symptoms, and risk factors in a representative cohort of children and adolescents in the canton of Zurich, Switzerland, shortly after re-opening of the school system and thereafter. The study also investigates antibodies to SARS-CoV-2 in parents of the children and school personnel.

Detailed description: The role of children and adolescents in the transmission of SARS-CoV-2 remains highly unclear and has been a key question since the early days of the pandemic. It has important consequences for policy decisions, especially concerning the opening of the schools, sport facilities and intergenerational contacts. However, the information on true infection rate and seroprevalence of SARS-CoV-2 is not known in children in Switzerland (and globally), as testing was limited to risk groups and those with SARS-CoV-2 coronavirus disease 2019 (COVID-19) related symptoms. In addition, indications for testing were not uniform and handled heterogeneously. Hence, it is not known whether children are less frequently infected or simply less symptomatic.

This study builds up a system to monitor the seroprevalence of SARS-CoV-2 in children and adolescents who attend school in the canton of Zürich, Switzerland. The investigators aim to assess children of randomly selected primary and secondary schools during the first weeks of re-entering school from all districts of the canton of Zurich in June and July 2020, after the temporary closure due to COVID-19 pandemic, and again in October/November 2020, February/March 2021, November/December 2021, and again in the second half of 2022. The detailed time plan including possible further assessments will be defined depending on the evolution of the pandemic (e.g., 2023). A follow-up capturing health status, symptoms and behaviors over time is important, since it is currently under investigation whether persons may be at risk for reinfection. Thus, a longitudinal assessment is crucial to determine the extent and duration of immunity.

In addition, the seroprevalence of SARS-CoV-2 in the parents of the participating children will be tested in August/September 2020, to examine clusters of infections in households. Seroprevalence of SARS-CoV-2 in school personnel will be tested in August/September 2020 and subsequently in October/November 2020 and February/March 2021, to examine temporal changes in the seroprevalences in the whole school community. Further testing of adults is not planned.

In different subpopulations, further in-depth analysis of immunity markers will be performed in the future.

This study complements the ongoing coordinated efforts of seroprevalence studies in adults in Switzerland, through the Swiss School of Public Health (SSPH+) coordinated CORONA IMMUNITAS studies.

Eligibility criteria: Inclusion Criteria:

* Any school child residing in Switzerland aged 5 years or older and attending a consenting to participate public or private school that hosts classes of interest (grade 1 through 9) in the canton of Zürich.
* Parents of participating children.
* Personnel employed in the participating schools.
* No acute respiratory and SARS-CoV-2 infection:

  * In case of unknown respiratory infection, no presence of symptoms for at least 48 hours.
  * In case of confirmed SARS-CoV-2 infection: inclusion at the earliest 21 days from PCR-positive diagnosis after the onset of potential symptoms and no presence of symptoms for at least 48 hours (according to Standard of Care).
* Informed consent of parents or legal guardians and children, or the adult participant.

Exclusion Criteria:

* No informed consent by schools or children, or the adult participant.
* Schools with \<40 students in one of the sampled grades (1, 2, 4, 5, 7, or 8).
* Children of Kindergarten age and younger.
* Suspicion of acute COVID-19 infection.
* Special need schools.

Primary outcomes:
measure: Seroprevalence of SARS-CoV-2 IgG, IgM and/or IgA antibodies
timeFrame: at inclusion
measure: Seroprevalence of SARS-CoV-2 IgG, IgM and/or IgA antibodies
timeFrame: Month 4-5
measure: Seroprevalence of SARS-CoV-2 IgG, IgM and/or IgA antibodies
timeFrame: Month 8-9
measure: Seroprevalence of SARS-CoV-2 IgG antibodies
timeFrame: Month 17-18
measure: Seroprevalence of SARS-CoV-2 IgG antibodies
timeFrame: Month 24-30
Secondary outcomes:
measure: Presence of self-reported symptoms
timeFrame: at inclusion
measure: Proportion of seropositive children reporting COVID-19 related symptoms from January 2020
timeFrame: at inclusion
measure: Presence of self-reported symptoms
timeFrame: within 36 months of follow-up
measure: Incidence of symptoms in initially seropositive participants
timeFrame: within 36 months of follow-up
measure: Proportion of participants, seronegative at inclusion, with symptoms in the follow-up
timeFrame: within 36 months of follow-up
measure: Presence of risk factors for infection at inclusion (assessment via custom questionnaire)
timeFrame: at inclusion
measure: Presence of risk factors for infection during follow-up (assessment via custom questionnaire)
timeFrame: within 36 months of follow-up
measure: Self-reported lifestyle changes of participants at inclusion
timeFrame: at inclusion
measure: Self-reported lifestyle changes of participants during follow-up
timeFrame: within 36 months of follow-up
measure: Self-reported mental well-being (KINDL questionnaire)
timeFrame: within 36 months of follow-up
measure: Self-reported mental well-being (HBSC questionnaire)
timeFrame: within 36 months of follow-up
measure: Self-reported quality of life (KINDL questionnaire)
timeFrame: within 36 months of follow-up
measure: Prevalence of seropositive SARS-Cov-2 clusters in schools at inclusion
timeFrame: at inclusion
measure: Incidence of seropositive SARS-Cov-2 clusters in schools during the follow-up
timeFrame: within 36 months of follow-up
measure: Change in seropositive participants within school or class, depending on the initial proportion of seropositive participants
timeFrame: within 36 months of follow-up
measure: Effect of risk factors and preventive measures on SARS-CoV-2 infection incidence within schools
timeFrame: within 36 months of follow-up
Other outcomes:
measure: Evolution of cellular immunity over time
timeFrame: within 36 months of follow-up
measure: Long COVID
timeFrame: within 36 months of follow-up
Locations:
city: Zurich
country: Switzerland
facility: Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich
Study officials:
affiliation: University of Zurich
name: Susi Kriemler, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ulyte A, Radtke T, Abela IA, Haile SR, Berger C, Huber M, Schanz M, Schwarzmueller M, Trkola A, Fehr J, Puhan MA, Kriemler S. Clustering and longitudinal change in SARS-CoV-2 seroprevalence in school children in the canton of Zurich, Switzerland: prospective cohort study of 55 schools. BMJ. 2021 Mar 17;372:n616. doi: 10.1136/bmj.n616.
citation: Radtke T, Ulyte A, Puhan MA, Kriemler S. Long-term Symptoms After SARS-CoV-2 Infection in Children and Adolescents. JAMA. 2021 Jul 15;326(9):869-71. doi: 10.1001/jama.2021.11880. Online ahead of print.
citation: Ammann P, Ulyte A, Haile SR, Puhan MA, Kriemler S, Radtke T. Perceptions towards mask use in school children during the SARS-CoV-2 pandemic: descriptive results from the longitudinal Ciao Corona cohort study. Swiss Med Wkly. 2022 Apr 20;152:w30165. doi: 10.4414/smw.2022.w30165. eCollection 2022 Apr 11.
citation: Peralta GP, Camerini AL, Haile SR, Kahlert CR, Lorthe E, Marciano L, Nussbaumer A, Radtke T, Ulyte A, Puhan MA, Kriemler S. Lifestyle Behaviours of Children and Adolescents During the First Two Waves of the COVID-19 Pandemic in Switzerland and Their Relation to Well-Being: An Observational Study. Int J Public Health. 2022 Sep 8;67:1604978. doi: 10.3389/ijph.2022.1604978. eCollection 2022.
citation: Blankenberger J, Haile SR, Puhan MA, Berger C, Radtke T, Kriemler S, Ulyte A. Prediction of Past SARS-CoV-2 Infections: A Prospective Cohort Study Among Swiss Schoolchildren. Front Pediatr. 2021 Aug 16;9:710785. doi: 10.3389/fped.2021.710785. eCollection 2021.
citation: Ulyte A, Radtke T, Abela IA, Haile SR, Braun J, Jung R, Berger C, Trkola A, Fehr J, Puhan MA, Kriemler S. Seroprevalence and immunity of SARS-CoV-2 infection in children and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study. Int J Public Health. 2020 Dec;65(9):1549-1557. doi: 10.1007/s00038-020-01495-z. Epub 2020 Oct 15.
citation: Haile SR, Gunz S, Peralta GP, Ulyte A, Raineri A, Rueegg S, Yasenok V, Radtke T, Puhan MA, Kriemler S. Health-Related Quality of Life and Adherence to Physical Activity and Screen Time Recommendations in Schoolchildren: Longitudinal Cohort Ciao Corona. Int J Public Health. 2023 Jul 19;68:1606033. doi: 10.3389/ijph.2023.1606033. eCollection 2023.
citation: Haile SR, Peralta GP, Raineri A, Rueegg S, Ulyte A, Puhan MA, Radtke T, Kriemler S. Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: Results from a prospective longitudinal cohort study. Eur J Pediatr. 2024 May;183(5):2273-2283. doi: 10.1007/s00431-024-05459-w. Epub 2024 Feb 27.
citation: Haile SR, Raineri A, Rueegg S, Radtke T, Ulyte A, Puhan MA, Kriemler S. Heterogeneous evolution of SARS-CoV-2 seroprevalence in school-age children: Results from the school-based cohort study Ciao Corona in November-December 2021 in the canton of Zurich. Swiss Med Wkly. 2023 Jan 30;153:40035. doi: 10.57187/smw.2023.40035.
citation: Ulyte A, Radtke T, Abela IA, Haile SR, Blankenberger J, Jung R, Capelli C, Berger C, Frei A, Huber M, Schanz M, Schwarzmueller M, Trkola A, Fehr J, Puhan MA, Kriemler S. Variation in SARS-CoV-2 seroprevalence across districts, schools and classes: baseline measurements from a cohort of primary and secondary school children in Switzerland. BMJ Open. 2021 Jul 26;11(7):e047483. doi: 10.1136/bmjopen-2020-047483.
citation: Kriemler S, Ulyte A, Ammann P, Peralta GP, Berger C, Puhan MA, Radtke T. Surveillance of Acute SARS-CoV-2 Infections in School Children and Point-Prevalence During a Time of High Community Transmission in Switzerland. Front Pediatr. 2021 Mar 16;9:645577. doi: 10.3389/fped.2021.645577. eCollection 2021.
citation: Raineri A, Radtke T, Rueegg S, Haile SR, Menges D, Ballouz T, Ulyte A, Fehr J, Cornejo DL, Pantaleo G, Pellaton C, Fenwick C, Puhan MA, Kriemler S. Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study. Nat Commun. 2023 Nov 27;14(1):7764. doi: 10.1038/s41467-023-43330-y.