Pulmonary Function and Long-Term Respiratory Symptoms in Children and Adolescents After COVID-19

  1. Leona Knoke
  2. Anne Schlegtendal
  3. Christoph Maier
  4. Lynn Eitner
  5. Thomas Lücke
  6. Folke Brinkmann

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Abstract

Persistent respiratory symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults are frequent, and there can be long-term impairment of pulmonary function. To date, only preliminary evidence is available on persistent respiratory sequelae of SARS-CoV-2 in children and adolescents. Our objective was to examine the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infections on pulmonary function in this age group in a single-center, controlled, prospective study.

Methods

Participants with serological or polymerase chain reaction-based evidence of SARS-CoV-2 infection were recruited from a population-based study of seroconversion rates. Multiple-breath washout (MBW), body plethysmography, and diffusion capacity testing were performed for children and adolescents. Participants were interviewed about their symptoms during the acute phase of infection and long-lasting symptoms. Cases were compared with SARS-CoV-2 seronegative controls from the same population-based study with and without history of respiratory infection within 6 months prior to assessment. Primary endpoints were differences in pulmonary function, including diffusion capacity and MBW, between participants with and without evidence of SARS-CoV-2 infection. Secondary endpoints included correlation between lung function and long-lasting symptoms as well as disease severity.

Findings

In total, 73 seropositive children and adolescents (5–18 years) were recruited after an average of 2.6 months (range 0.4–6.0) following SARS-CoV-2 infection. Among 19 patients (27.1%) who complained of persistent or newly emerged symptoms since SARS-CoV-2, 8 (11.4%) reported respiratory symptoms. No significant differences were detected in frequency of abnormal pulmonary function when comparing cases with 45 controls, including 14 (31.1%) with a history of previous infection (SARS-CoV-2: 12, 16.4%; controls: 12, 27.7%; odds ratio 0.54, 95% confidence interval 0.22–1.34). Only two patients with persistent respiratory symptoms showed abnormal pulmonary function. Multivariate analysis revealed reduced forced vital capacity ( p = 0.012) in patients with severe SARS-CoV-2 infection.

Interpretation

Pulmonary function is rarely impaired in children and adolescents after SARS-CoV-2 infection, except from those with severe infection, and did not differ between SARS-CoV-2 and other previous infections, suggesting that SARS-CoV-2 is not more likely to cause pulmonary sequelae than other infections. The discrepancy between persisting respiratory symptoms and normal pulmonary function suggests a different underlying pathology such as dysfunctional breathing.

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  1. Version published to 10.3389/fped.2022.851008
  2. ScreenIT

    SciScore for 10.1101/2021.06.22.21259273: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Exclusion criteria were inability to perform lung function testing and missing written consent.
    IRB: Ethical approval: The ethics committee of the Ruhr-University, Bochum, Germany, approved the project (register number: 20-6927).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingAll pulmonary function tests were done by specially trained staff and assessed by two paediatric pneumologists blinded to the patient’s SARS-CoV-2 status.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analysis were performed using SPSS version 27 (SPSS for Windows, SPSS Inc., Chicago, IL, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Limitations of this single-centre design with a rather small sample size include age-dependent inconsistencies in pulmonary function performance, patient-reported symptoms and lack of information on long-term outcome of symptoms in controls. Further, our cohort did not include children and adolescents with critical respiratory involvement during acute COVID-19. To our knowledge, our study is the first to compare pulmonary function in symptomatic and asymptomatic children and adolescents with and without evidence of SARS-CoV-2 infection; no difference between these two groups was observed. Even most patients with persistent respiratory symptoms did not show impaired lung capacity. Severity of infection proved to be the only predictor for mild pulmonary function changes. To conclude, our findings suggest that children and adolescents after SARS-CoV-2 infection do not suffer from persistent deterioration of respiratory function, including body plethysmography, multiple-breath washout and diffusion capacity testing. Further studies with a larger, more representative cohort (including patients with critical respiratory involvement) and over a longer period are needed for better understanding of the respiratory long-term impairment after SARS-CoV-2 infection in children and adolescents. The discrepancy between subjective persistent respiratory complaints and normal pulmonary function might be caused by functional respiratory disorders, for example hyperventilation, as already descr...

    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.

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  3. Version published to 10.1101/2021.06.22.21259273v1 on medRxiv