Virologic Features of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

  1. Lael M Yonker
  2. Julie Boucau
  3. James Regan
  4. Manish C Choudhary
  5. Madeleine D Burns
  6. Nicola Young
  7. Eva J Farkas
  8. Jameson P Davis
  9. Peter P Moschovis
  10. T Bernard Kinane
  11. Alessio Fasano
  12. Anne M Neilan
  13. Jonathan Z Li
  14. Amy K Barczak

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Abstract

Background

Data on pediatric coronavirus disease 2019 (COVID-19) has lagged behind adults throughout the pandemic. An understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics in children would enable data-driven public health guidance.

Methods

Respiratory swabs were collected from children with COVID-19. Viral load was quantified by reverse-transcription polymerase chain reaction (RT-PCR); viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences.

Results

One hundred ten children with COVID-19 (median age, 10 years [range, 2 weeks–21 years]) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first 5 days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified.

Conclusions

Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

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  1. Version published to 10.1093/infdis/jiab509
  2. Version published to 10.1101/2021.05.30.21258086v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.30.21258086: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Sample collection: Infants, children and adolescents < 22 years of age presenting to Massachusetts General Hospital urgent care clinics or the hospital with COVID-19 as determined by PCR testing of nasal specimens (4/2020-4/2021) were offered enrollment in the Institutional Review Board-approved MGH Pediatric COVID-19 Biorepository (IRB # 2020P000955).
    Consent: After informed consent, and assent when appropriate, was obtained verbally, a nasopharyngeal, oropharyngeal and/or anterior nares swab was obtained and placed in phosphate buffered saline.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    For TCID50 measurements conducted in parallel, 25uL of the Spin-X flow-through was used to inoculate Vero-E6 cells in a 96w plate in the presence of 5ug/mL of polybrene (Santa Cruz Biotechnology) using 5-fold dilutions (5-1 to 5-6) and 4 repeats for each sample.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Clinical data collection: Demographic and clinical factors were recorded through a combination of manual charts reviews and data extraction from electronic health records (EHR), then collected in a REDCap database [15] through the Partners Electronic Health Record Registry of Pediatric COVID-19 Disease (IRB # 2020P003588).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Nucleotide sequence alignment was performed with MAFFT (multiple alignment using fast Fourier transform) [19]
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Best-fit nucleotide substitution GTR+G+I was used for the datasets using model selection in IQ-Tree followed by maximum likelihood phylogenetic tree construction using IQ-Tree web server with 1000-bootstrap replicates [20].
    IQ-Tree
    suggested: (IQ-TREE, RRID:SCR_017254)
    Analysis: All statistical analyses were performed using parametric comparisons in GraphPad Prism (Version 9.1.1), including Pearson correlation, ANOVA with multiple comparisons, and unpaired t test.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.05.30.21258086v1 on medRxiv