SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children

  1. Aaron M. Frutos
  2. John Kubale
  3. Guillermina Kuan
  4. Sergio Ojeda
  5. Nivea Vydiswaran
  6. Nery Sanchez
  7. Miguel Plazaola
  8. May Patel
  9. Roger Lopez
  10. Angel Balmaseda
  11. Aubree Gordon

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Abstract

It has been proposed that as SARS-CoV-2 transitions to endemicity, children will represent the greatest proportion of SARS-Co-V-2 infections as they currently do with endemic coronavirus infections. While SARS-CoV-2 infection severity is low for children, it is unclear if SARS-CoV-2 infections are distinct in symptom presentation, duration, and severity from endemic coronavirus infections in children. We compared symptom risk and duration of endemic human coronavirus (HCoV) infections from 2011–2016 with SARS-CoV-2 infections from March 2020-September 2021 in a Nicaraguan pediatric cohort. Blood samples were collected from study participants annually in February-April. Respiratory samples were collected from participants that met testing criteria. Blood samples collected in were tested for SARS-CoV-2 antibodies and a subset of 2011–2016 blood samples from four-year-old children were tested for endemic HCoV antibodies. Respiratory samples were tested for each of the endemic HCoVs from 2011–2016 and for SARS-CoV-2 from 2020–2021 via rt-PCR. By April 2021, 854 (49%) cohort participants were ELISA positive for SARS-CoV-2 antibodies. Most participants had antibodies against one alpha and one beta coronavirus by age four. We observed 595 symptomatic endemic HCoV infections from 2011–2016 and 121 symptomatic with SARS-CoV-2 infections from March 2020-September 2021. Symptom presentation of SARS-CoV-2 infection and endemic coronavirus infections were very similar, and SARS-CoV-2 symptomatic infections were as or less severe on average than endemic HCoV infections. This suggests that, for children, SARS-CoV-2 may be just another endemic coronavirus. However, questions about the impact of variants and the long-term effects of SARS-CoV-2 remain.

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  1. Version published to 10.1371/journal.pgph.0000414
  2. Version published to 10.1101/2021.12.09.21267537v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.09.21267537: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Institutional review boards at the Nicaraguan Ministry of Health and the University of Michigan approved this study.
    Consent: Parents/guardians of participants provided written informed consent and participants aged ≥6 years provided verbal assent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To confirm our assumption that endemic HCoV infection rates are high in the cohort, we tested a random subset of 100 blood samples from four-year-old’s from 2011-2016; using protocols for an enzyme-linked immunosorbent assay (ELISA) developed at Mount Sinai (8), we tested samples for antibody response to the spike protein for each of the four endemic HCoV (alpha: NL63, and 229E, beta: OC43 and HKU1).
    HKU1
    suggested: None
    To confirm that SARS-CoV-2 infections rates were also high, we tested the 2021 blood samples for SARS-CoV-2 antibodies as described previously. (9) Parents/guardians agreed to bring participants to the health center at the first signs of fever.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    We used SAS version 9.4 (SAS Institute Inc.) to calculate risk differences and ratios and R version 4.1.0 to create figures and conduct all other analyses.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    However, this study does have some limitations. First, using data from this community-based cohort study we were not powered to detect the most severe manifestations of SARS-CoV-2 including death or Multisystem Inflammatory Syndrome in Children (MIS-C) and other rare outcomes. (15, 16) Second, our analysis did not include genetic sequencing preventing us from assessing the importance of variants in presentation and severity of SARS-CoV-2 illness. We did compare SARS-CoV-2 symptom presentation, severity, and duration by year and found little or no difference. Finally, while our study does not evaluate asymptomatic illness for endemic HCoVs, our results were consistent with other research, showing that childhood HCoVs are ubiquitous and that symptomatic cases represent only a small proportion of infections, as with SARS-CoV-2. (12) In this study, we observed that symptomatic SARS-CoV-2 infections at the community level are very similar to symptomatic endemic HCoV infections in symptom presentation. Among children in a setting with a high SARS-CoV-2 infection rate, symptomatic SARS-CoV-2 infections are on average as or less severe as endemic HCoV infections. These findings support the hypothesis that SARS-CoV-2 may be like another endemic HCoV for children—most children will be asymptomatic with rare cases of severe symptomatic illness. This does not mean SARS-CoV-2 in children is not important. There are many unknowns about the long-term effects and impact of repeat infections ...

    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 10.1101/2021.12.09.21267537v1 on medRxiv