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Virology

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs

Larry K. Kociolek, William J. Muller, Rebecca Yee, Jennifer Dien Bard, Cameron A. Brown, Paula A. Revell, Hanna Wardell, Timothy J. Savage, Sarah Jung, Samuel Dominguez, Bijal A. Parikh, Robert C. Jerris, Sue C. Kehl, Aaron Campigotto, Jeffrey M. Bender, Xiaotian Zheng, Emily Muscat, Matthew Linam, Lisa Abuogi, Christiana Smith, Kelly Graff, Ariel Hernandez-Leyva, David Williams, Nira R. Pollock
Randall Hayden, Editor
Larry K. Kociolek
aDivision of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
cNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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  • ORCID record for Larry K. Kociolek
William J. Muller
aDivision of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
cNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Rebecca Yee
gDepartment of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, California, USA
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Jennifer Dien Bard
gDepartment of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, Los Angeles, California, USA
iKeck School of Medicine, University of Southern California, Los Angeles, California, USA
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Cameron A. Brown
jTexas Children’s Hospital, Houston, Texas, USA
kBaylor College of Medicine, Houston, Texas, USA
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Paula A. Revell
jTexas Children’s Hospital, Houston, Texas, USA
kBaylor College of Medicine, Houston, Texas, USA
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Hanna Wardell
dDivision of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts, USA
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Timothy J. Savage
dDivision of Infectious Diseases, Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts, USA
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Sarah Jung
lDepartment of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, Colorado, USA
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Samuel Dominguez
lDepartment of Pathology and Laboratory Medicine, Children’s Hospital Colorado, Aurora, Colorado, USA
mDepartment of Pediatrics, Division of Infectious Diseases, University of Colorado, Aurora, Colorado, USA
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Bijal A. Parikh
nDepartment of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA
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Robert C. Jerris
pDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
qChildren’s Healthcare of Atlanta, Atlanta, Georgia, USA
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Sue C. Kehl
sDepartment of Pathology, Children’s Wisconsin, Milwaukee, Wisconsin, USA
tMedical College of Wisconsin, Milwaukee, Wisconsin, USA
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Aaron Campigotto
uDepartment of Paediatric Laboratory Medicine, Hospital for Sick Kids, Toronto, Canada
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Jeffrey M. Bender
hDivision of Infectious Diseases, Children’s Hospital Los Angeles, Los Angeles, California, USA
iKeck School of Medicine, University of Southern California, Los Angeles, California, USA
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Xiaotian Zheng
bDepartment of Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
cNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Emily Muscat
aDivision of Infectious Diseases, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
bDepartment of Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
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Matthew Linam
qChildren’s Healthcare of Atlanta, Atlanta, Georgia, USA
rDivision of Pediatric Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
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Lisa Abuogi
mDepartment of Pediatrics, Division of Infectious Diseases, University of Colorado, Aurora, Colorado, USA
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Christiana Smith
mDepartment of Pediatrics, Division of Infectious Diseases, University of Colorado, Aurora, Colorado, USA
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Kelly Graff
mDepartment of Pediatrics, Division of Infectious Diseases, University of Colorado, Aurora, Colorado, USA
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Ariel Hernandez-Leyva
oDivision of Allergy and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA
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David Williams
eInstitutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts, USA
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Nira R. Pollock
fDepartment of Laboratory Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
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Randall Hayden
St. Jude Children's Research Hospital
Roles: Editor
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DOI: 10.1128/JCM.02593-20
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ABSTRACT

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

FOOTNOTES

    • Received 12 October 2020.
    • Returned for modification 16 October 2020.
    • Accepted 21 October 2020.
    • Accepted manuscript posted online 22 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs
Larry K. Kociolek, William J. Muller, Rebecca Yee, Jennifer Dien Bard, Cameron A. Brown, Paula A. Revell, Hanna Wardell, Timothy J. Savage, Sarah Jung, Samuel Dominguez, Bijal A. Parikh, Robert C. Jerris, Sue C. Kehl, Aaron Campigotto, Jeffrey M. Bender, Xiaotian Zheng, Emily Muscat, Matthew Linam, Lisa Abuogi, Christiana Smith, Kelly Graff, Ariel Hernandez-Leyva, David Williams, Nira R. Pollock
Journal of Clinical Microbiology Dec 2020, 59 (1) e02593-20; DOI: 10.1128/JCM.02593-20

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Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs
Larry K. Kociolek, William J. Muller, Rebecca Yee, Jennifer Dien Bard, Cameron A. Brown, Paula A. Revell, Hanna Wardell, Timothy J. Savage, Sarah Jung, Samuel Dominguez, Bijal A. Parikh, Robert C. Jerris, Sue C. Kehl, Aaron Campigotto, Jeffrey M. Bender, Xiaotian Zheng, Emily Muscat, Matthew Linam, Lisa Abuogi, Christiana Smith, Kelly Graff, Ariel Hernandez-Leyva, David Williams, Nira R. Pollock
Journal of Clinical Microbiology Dec 2020, 59 (1) e02593-20; DOI: 10.1128/JCM.02593-20
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KEYWORDS

COVID-19
SARS-CoV-2
diagnostics
pediatric infectious disease

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