Persistent symptoms among children and adolescents with and without anti-SARS-CoV-2 antibodies: a population-based serological study in Geneva, Switzerland

  1. Roxane Dumont
  2. Mayssam Nehme
  3. Elsa Lorthe
  4. Carlos de Mestral
  5. Viviane Richard
  6. Hélène Baysson
  7. Francesco Pennacchio
  8. Julien Lamour
  9. Claire Semaani
  10. María-Eugenia Zaballa
  11. Nick Pullen
  12. Anne Perrin
  13. Arnaud G. L’Huillier
  14. Klara M. Posfay-Barbe
  15. Idris Guessous
  16. Silvia Stringhini

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Abstract

Background

It is now established that a significant proportion of adults experience persistent symptoms after SARS-CoV-2 infection. However, evidence for children and adolescents is still inconclusive. In this population-based study, we examine the proportion of children and adolescents reporting persistent symptoms after SARS-CoV-2 infection, as assessed by serological status, and compare this to a seronegative control group.

Methods

We conducted a serosurvey in June-July 2021, recruiting 660 children and adolescents from 391 households selected randomly from the Geneva population. We tested participants for anti-SARS-CoV-2 antibodies targeting the nucleocapsid (N) protein to determine previous infection. A parent filled a questionnaire including questions on COVID-19-related symptoms lasting at least 2 weeks.

Findings

Among children seropositive for anti-SARS-CoV-2 antibodies, the sex- and age-adjusted prevalence of symptoms lasting longer than two weeks was 18.3%, compared to 11.1% among seronegative children (prevalence difference (ΔaPrev)=7.2%, 95%CI:1.5-13.0). Main symptoms declared among seropositive children were fatigue (11.5%) and headache (11.1%). For 8.6% (aPrev, 95%CI: 4.7-12.5) of seropositives, these symptoms were declared to be highly limiting of daily activities. Adolescents aged 12-17 years had a higher adjusted prevalence of persistent symptoms (aPrev=29.1%, 95%CI:19.4-38.7) than younger children. Comparing seropositive and seronegative adolescents, the estimated prevalence of symptoms lasting over four weeks is 4.4% (ΔaPrev, 95%CI:-3.8-13.6).

Interpretation

A significant proportion of children aged 12 to 17 years had symptoms lasting over two weeks after SARS-CoV-2 infection, with an estimated prevalence of symptoms lasting over 4 weeks of 4.4% in this age group. This represents a large number of adolescents in absolute terms, and should raise concern in the context of unknown long-term evolution of symptoms. Younger children appear to experience long-lasting symptoms less frequently, as no difference was observed between the seropositive and seronegative sample. Further studies with larger samples sizes are needed.

Funding

Swiss Federal Office of Public Health, Geneva General Directorate of Health, HUG Private Foundation, SSPH+, Fondation des Grangettes.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.23.21268298: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: After providing written informed consent, participants provided a venous blood sample.
    Sex as a biological variablenot detected.
    RandomizationStudy population: Participants from a random sample of the general population of the state of Geneva, Switzerland, were invited to take part in a serological survey between June 1st and July 7th, 2021 [16].
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The Roche N serological test identifies anti-N antibodies, which are not produced following vaccination with mRNA vaccines used in Geneva to date, such as the Pfizer-BioNTech BNT162b2 and Moderna mRNA 1273 vaccines, and are therefore only detected if the individual was infected with SARS-CoV-2.
    anti-N
    suggested: None
    Statistical analysis: We compared the distribution of sociodemographic and COVID-19-related characteristics between children who tested positive for anti-SARS-CoV-2 antibodies and children who tested negative, overall and stratified into three age groups (2 to 5, 6 to 11 and 12 to 17).
    anti-SARS-CoV-2
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The study also has several limitations. First, it relies on parent-reported data on questionnaires without clinical assessment and objective measures. The presence and duration of persistent symptoms among children is based on the parental point of view, which can be subjective due to a potential memory bias and influenced by the parent’s background as well as the general household environment [21]. Also, the lack of information on the duration of persistent symptoms after four weeks as well as symptoms’ daily burden not being based on a standardized measure complicates the classification and diagnosis of long COVID. Finally, our sample is relatively small, with less than 10% of power to detect a difference of 1% in the prevalence of symptoms lasting more than 4 weeks between the seropositive and the seronegative sample.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.12.23.21268298v1 on medRxiv