Seroprevalence of SARS-CoV-2 antibodies and associated risk factors in children less than 6 years of age in the canton of Fribourg, Switzerland (COVPED study): a population-based cross-sectional study
BACKGROUND: To date, few data are available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and the role of early-life childcare arrangements in transmission of the virus. In this study, we assessed the SARS-CoV-2 seroprevalence in children less than 6 years of age in the canton of Fribourg and identified risk factors associated with seropositivity.
METHODS: The COVPED study is a population-based cross-sectional study in children less than 6 years of age living in the canton of Fribourg, Switzerland, who presented to a private paediatrician or the paediatric emergency department of the Fribourg Hospital during a 9-week period between 11 January and 14 March 2021. Immunoglobulin G antibodies against SARS-CoV-2 trimeric spike protein were measured in capillary blood samples using an in-house Luminex assay. A mean fluorescence intensity ratio of above 6 was considered as positive. Metadata was collected through electronic questionnaires. Logistic regression analysis was performed to assess the risk of seropositivity and associated factors.
RESULTS: A total of 871 children, with a median age of 33 months (range 6 days to 5 years 11 months) were included; 412 (47%) were female. Overall, 180 (21%, 95% confidence interval [CI] 18–24%) children were seropositive. Age as continuous variable was not associated with seropositivity risk, apart from a higher rate in children less than 3 months of age. Univariable analysis showed that female sex was associated with a lower seropositivity risk (unadjusted odds ratio [OR] 0.69, 95% CI 0.49–0.96; p = 0.03). Day-care attendance was also associated with a lower seropositivity risk (OR 0.67, 95% CI 0.47–0.95; p = 0.03), whereas all other childcare arrangements were not associated with seropositivity. No association was found between the number of children and adults present in extra-familial care and seropositivity. Multivariable analysis identified the number of household members above the age of 12 years being positive for SARS-CoV-2 as the main risk factor for seropositivity in children (adjusted odds ratio [aOR] 7.80, 95% CI 4.65–13.07; p <0.001 for one household member, aOR 22.07, 95% CI 13.49–36.11; p <0.001 for two household members and aOR 32.20, 95% CI 9.30–111.55; p <0.001 for three or more household members).
CONCLUSION: The number of household members tested positive for SARS-CoV-2 (PCR test) is the main exposure risk to seropositivity for children less than 6 years of age. But the family size is not associated with an increased risk of infection. In young children, extra-familial care does not increase the risk of becoming SARS-CoV-2 seropositive, neither does the number of contacts present in extra-familial care. As adults and children will be vaccinated and new virus variants will be circulating the risk of exposure for young children will likely change and needs further monitoring.
- Open database : COVID-19 Switzerland [Internet] Federal Office of Public Health (OFSP). c2021 [cited 2021 Aug 11]. Available from : https://www.covid19.admin.ch/fr/overview
- Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr;382(18):1708–20. https://doi.org/10.1056/NEJMoa2002032
- Qifang Bi, Yongsheng Wu, Shujiang Mei, Chenfei Y, Xuan Zou, Zhen Zhang, et al. Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. 2020;(January):19–21.
- Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J. 2020 May;39(5):355–68. https://doi.org/10.1097/INF.0000000000002660
- European Centre for Disease Prevention and Control. COVID-19 in children and the role of school settings in transmission - second update. [Internet]. 2021 Jul [cited 2021 Oct 7]. Available from : https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-in-children-and-the-role-of-school-settings-in-transmission-second-update.pdf
- L’Huillier AG, Torriani G, Pigny F, Kaiser L, Eckerle I. Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents. Emerg Infect Dis. 2020 Oct;26(10):2494–7. https://doi.org/10.3201/eid2610.202403
- Baggio S, L’Huillier AG, Yerly S, Bellon M, Wagner N, Rohr M, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load in the Upper Respiratory Tract of Children and Adults With Early Acute Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2021 Jul;73(1):148–50. https://doi.org/10.1093/cid/ciaa1157
- graphics.reuters.com. [Internet]. Reuters COVID-19 Tracker. c2021 [cited 2021 Oct 7]. Available from : https://graphics.reuters.com/world-coronavirus-tracker-and-maps/fr/countries-and-territories/switzerland/
- ffaes.ch. [Internet]. Switzerland : Protection concept for day care centers and after-school care facilities - Kibesuisse. c2020 [cited 2021 Oct 25]. Available from: http://ffaes.ch/fileadmin/user_upload/Documents/FFAES/WWW/Editors/CORONAVIRUS/2020.05.01_200430_Modele_conceptprotection_creches_parascolaire.pdf
- bdlf.fr.ch. [Internet]. Switzerland : Ordinance defining measures for the control of the coronavirus (COVID-19) - Canton of Fribourg. c2020 [cited 2021 Oct 25]. Available from: https://bdlf.fr.ch/app/fr/texts_of_law/821.40.21
- fr.ch. [Internet]. Switzerland : Protection concept for compulsory education from 1H-11H - Canton of Fribourg. c2020 [cited 2021 Oct 25]. Available from: https://www.fr.ch/sites/default/files/2020-05/20200506_Ecole_obligatoire_OCC_COVID_Plan_de_protection.pdf
- kibesuisse.ch. [Internet]. Switzerland : 8 Golden Rule - Kibesuisse. c2021 [cited 2021 Oct 25]. Available from: https://www.kibesuisse.ch/fileadmin/Dateiablage/kibesuisse_Dokumente/Corona/8_Golden_Rules_FR_A4.pdf
- Ulyte A, Radtke T, Abela IA, Haile SR, Braun J, Jung R, et al. 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):1549–57. https://doi.org/10.1007/s00038-020-01495-z
- Fontanet A, Tondeur L, Grant R, Temmam S, Madec Y, Bigot T, et al. SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission, France, January to April 2020. Euro Surveill. 2021 Apr;26(15):1–12. https://doi.org/10.2807/1560-7917.ES.2021.26.15.2001695
- Ludvigsson JF. Children are unlikely to be the main drivers of the COVID-19 pandemic - A systematic review. Acta Paediatr. 2020 Aug;109(8):1525–30. https://doi.org/10.1111/apa.15371
- Barcellini L, Forlanini F, Sangiorgio A, Gambacorta G, Alberti L, Meta A, et al. Does school reopening affect SARS-CoV-2 seroprevalence among school-age children in Milan? Folgori L, editor. PLoS One. 2021 Sep 2;16(9):1–6.
- Goldstein E, Lipsitch M, Cevik M. On the effect of age on the transmission of SARS-CoV-2 in households, schools, and the community. J Infect Dis. 2021 Feb;223(3):362–9. https://doi.org/10.1093/infdis/jiaa691
- Esposito S, Marchetti F, Lanari M, Caramelli F, De Fanti A, Vergine G, et al.; Working Group on COVID-19 in Pediatrics of the Emilia-Romagna Region (RE-CO-Ped). COVID-19 Management in the Pediatric Age: Consensus Document of the COVID-19 Working Group in Paediatrics of the Emilia-Romagna Region (RE-CO-Ped), Italy. Int J Environ Res Public Health. 2021 Apr;18(8):1–29. https://doi.org/10.3390/ijerph18083919
- Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, et al.; ptbnet COVID-19 Study Group. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020 Sep;4(9):653–61. https://doi.org/10.1016/S2352-4642(20)30177-2
- Zhu Y, Bloxham CJ, Hulme KD, Sinclair JE, Tong ZW, Steele LE, et al. A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters. Clin Infect Dis. 2021 Jun;72(12):e1146–53. https://doi.org/10.1093/cid/ciaa1825
- Li W, Zhang B, Lu J, Liu S, Chang Z, Peng C, et al. Characteristics of Household Transmission of COVID-19. Clin Infect Dis. 2020 Nov;71(8):1943–6. https://doi.org/10.1093/cid/ciaa450
- Maltezou HC, Vorou R, Papadima K, Kossyvakis A, Spanakis N, Gioula G, et al. Transmission dynamics of SARS-CoV-2 within families with children in Greece: A study of 23 clusters. J Med Virol. 2021 Mar;93(3):1414–20. https://doi.org/10.1002/jmv.26394
- Galow L, Haag L, Kahre E, Blankenburg J, Dalpke AH, Lück C, et al. Lower household transmission rates of SARS-CoV-2 from children compared to adults. J Infect. 2021 Jul;83(1):e34–6. https://doi.org/10.1016/j.jinf.2021.04.022
- Fenwick C, Croxatto A, Coste AT, Pojer F, André C, Pellaton C, et al. Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies. Subbarao K, editor. J Virol. 2021 Jan 13;95(3):1–12.
- corona-immunitas.ch. [Internet]. Switzerland : Corona Immunitas - choosing test. c2021 [cited 2021 Aug 11]. Available from: https://www.corona-immunitas.ch/aktuell/choosing-a-common-test/
- Open database : Canton of Fribourg [Internet]. Statistics on the population of the canton of Fribourg. c2020 [cited 2021 Dec 1]. Available from : http://appl.fr.ch/stat_statonline/portraitif/etape2.asp?Niveau=2&langue=fr&initMenu=1
- Crechesfribourg.ch. [Internet]. Fédération des crèches et garderies fribourgeoises [cited 2021 January 7]. Available from : p. https://www.crechesfribourg.ch/fr/contact
- corona-immunitas.ch. [Internet]. Switzerland : Corona Immunitas - results. c2021 [cited 2021 Oct 7]. Available from: https://www.corona-immunitas.ch/fr/programme/resultats/
- Ulyte A, Radtke T, Abela IA, Haile SR, Ammann P, Berger C, et al. Evolution of SARS-CoV-2 seroprevalence and clusters in school children from June 2020 to April 2021: prospective cohort study Ciao Corona. Swiss Med Wkly. 2021 Nov;151:w30092.
- Ulyte A, Radtke T, Abela IA, Haile SR, Berger C, Huber M, et al. 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;372(616):n616. https://doi.org/10.1136/bmj.n616
- Zinszer K, Mckinnon B, Bourque N, Pierce L, Saucier A, Otis A, et al. Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada. 2021;4(11):1–12.
- Ladhani SN, Baawuah F, Beckmann J, Okike IO, Ahmad S, Garstang J, et al. SARS-CoV-2 infection and transmission in primary schools in England in June-December, 2020 (sKIDs): an active, prospective surveillance study. Lancet Child Adolesc Health. 2021 Jun;5(6):417–27. https://doi.org/10.1016/S2352-4642(21)00061-4
- Waterfield T, Watson C, Moore R, Ferris K, Tonry C, Watt A, et al. Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study. Arch Dis Child. 2021 Jul;106(7):680–6. https://doi.org/10.1136/archdischild-2020-320558
- Gudbjartsson DF, Helgason A, Jonsson H, Magnusson OT, Melsted P, Norddahl GL, et al. Spread of SARS-CoV-2 in the Icelandic Population. N Engl J Med. 2020 Jun;382(24):2302–15. https://doi.org/10.1056/NEJMoa2006100
- Jutzeler CR, Bourguignon L, Weis CV, Tong B, Wong C, Rieck B, et al. Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020 Sep - Oct;37:101825. https://doi.org/10.1016/j.tmaid.2020.101825
- Abate BB, Kassie AM, Kassaw MW, Aragie TG, Masresha SA. Sex difference in coronavirus disease (COVID-19): a systematic review and meta-analysis. BMJ Open. 2020 Oct;10(10):e040129. https://doi.org/10.1136/bmjopen-2020-040129
- Bienvenu LA, Noonan J, Wang X, Peter K. Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities. Cardiovasc Res. 2020 Dec;116(14):2197–206. https://doi.org/10.1093/cvr/cvaa284