Predictive Value of Isolated Symptoms for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children Tested During Peak Circulation of the Delta Variant

  1. Adrianna L Westbrook
  2. Laura C Benedit
  3. Jennifer K Frediani
  4. Mark A Griffiths
  5. Nabeel Y Khan
  6. Joshua M Levy
  7. Claudia R Morris
  8. Christina A Rostad
  9. Cheryl L Stone
  10. Julie Sullivan
  11. Miriam B Vos
  12. Jean Welsh
  13. Anna Wood
  14. Greg S Martin
  15. Wilbur Lam
  16. Nira R Pollock

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Abstract

Background

Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms.

Methods

Participants aged <18 years presenting for clinical SARS-CoV-2 molecular testing in 6 sites in urban/suburban/rural Georgia (July–October, 2021; Delta variant predominant) were queried about individual symptoms. Participants were classified into 3 groups: asymptomatic, 1 symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the 3 groups were compared. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for isolated symptoms were calculated by fitting a saturated Poisson model.

Results

Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70–13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66–10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI, .52–1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively.

Conclusions

With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value.

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  1. Version published to 10.1093/cid/ciac112
  2. ScreenIT

    SciScore for 10.1101/2021.12.17.21267993: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Patients aged 0 to 18 years old presenting to one of six ambulatory testing sites in Georgia (two urban and three suburban sites in the Atlanta area and one rural site in Blairsville) of the Atlanta Center of Microsystems Engineered Point-of-Care Technologies, the test verification center of the NIH-funded Rapid Acceleration of Diagnostics (RADx) Initiative, between July 4th and October 15th, 2021 were prospectively enrolled following informed consent and assent (as applicable per age) and participated in the following procedures: clinical nasopharyngeal PCR testing for SARS-CoV-2, detailed review of symptoms present at the time of clinical testing and overall symptom duration, and collection of additional samples for future research testing under the RADx program [7, 8].
    IRB: This study was approved by the Institutional Review Boards at Emory University (STUDY00000932) and Children’s Healthcare of Atlanta (IRB#00001082).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Graphs were created with RStudio (Boston, MA) and the ggplot2 package ([10] New York, NY).
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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 include that the study was relatively small, limiting numbers for each individual isolated symptom and for subgroup analysis, and we did not have information on the severity of each symptom nor on reasons for testing in asymptomatic children. We did not include data on Ct values or viral loads in the positive samples, both due to missing data and because many different PCR assays were used for clinical testing, which would have made these data difficult to combine for analysis. We did not do sequencing to confirm that the delta variant strain was responsible for the SARS-CoV-2 infections in these children, but the time window selected is consistent with the majority having been due to this variant [9] (prior studies similarly used time windows as a proxy for variant circulation [6]). We had too few vaccinated children in this study to draw conclusions about symptom presentation in this subgroup of children (prior studies similarly included predominantly unvaccinated children [6]). The study was performed in a region with high prevalence of the delta variant and in a population with a high proportion of known or suspected close contact, with variable local testing requirements and testing availabilities, so the population who presented for testing may not be fully generalizable to other settings (including settings with lower disease/exposure prevalence or other circulating variants). Though the high exposure rates might suggest that some patients presented for tes...

    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.

  3. Version published to 10.1101/2021.12.17.21267993 on medRxiv