[Skip to Content]
[Skip to Content Landing]

Assessment of Clinical and Virological Characteristics of SARS-CoV-2 Infection Among Children Aged 0 to 4 Years and Their Household Members

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Do community-acquired SARS-CoV-2 infections differ in adults and children aged 0 to 4 years with respect to incidence, symptoms, and detected viral load?

Findings  In this cohort study of 690 participants from 175 households in Maryland conducted from November 2020 to October 2021, 54 incident SARS-CoV-2 infections were detected in 8.6% of children aged 0 to 4 years, 11.0% of children aged 5 to 17 years, and 6.3% of adults. Children were more frequently asymptomatic or mildly symptomatic than adults; highest detected viral loads correlated with the number of symptoms in adults but not in young children.

Meaning  This study’s findings suggest that symptomatic screening for SARS-CoV-2 infection may be insufficient to control outbreaks in settings in which young children congregate.

Abstract

Importance  Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies.

Objective  To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults.

Design, Setting, and Participants  This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies.

Main Outcomes and Measures  Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage.

Results  Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006).

Conclusions and Relevance  In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: June 10, 2022.

Published: August 31, 2022. doi:10.1001/jamanetworkopen.2022.27348

Correction: This article was corrected on September 15, 2022, to correct a sentence in the Discussion.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Karron RA et al. JAMA Network Open.

Corresponding Author: Ruth A. Karron, MD, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, 624 N Broadway, Baltimore, MD 21205 (rkarron@jhu.edu).

Author Contributions: Dr Karron and Ms Hetrich had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Karron, Knoll, Meece, Dawood.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Karron, Na, Schappell, Lee.

Critical revision of the manuscript for important intellectual content: Karron, Hetrich, Knoll, Meece, Hanson, Tong, Lee, Veguilla, Dawood.

Statistical analysis: Hetrich, Na, Knoll.

Obtained funding: Meece.

Administrative, technical, or material support: Schappell, Meece, Tong, Lee, Veguilla, Dawood.

Supervision: Karron, Knoll, Meece, Dawood.

Conflict of Interest Disclosures: Dr Karron reported receiving grants from the Centers for Disease Control and Prevention (CDC) during the conduct of the study. Ms Hetrich reporting receiving grants from the CDC during the conduct of the study. Dr Knoll reported receiving grants from the CDC during the conduct of the study. Ms Schappell reported receiving grants from the CDC during the conduct of the study. Dr Meece reported receiving grants from the CDC during the conduct of the study. Ms Hanson reported receiving grants from the CDC during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by grant 75D30120C08737 from the CDC (Dr Karron via Johns Hopkins University).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: SEARCH Study Team members are listed in Supplement 2.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Additional Contributions: We are grateful to the SEARCH households for their dedicated participation in this study and to Annapolis Pediatrics, Columbia Medical Practice, Dundalk Pediatrics, and Johns Hopkins Community Physicians for allowing us to recruit households from their practices. We also thank the Department of Pathology, Johns Hopkins University School of Medicine, for performing the SARS-CoV-2 Roche Elecsys assays.

References
1.
Cucinotta  D , Vanelli  M . WHO declares COVID-19 a pandemic.  Acta Biomed. 2020;91(1):157-160.PubMed
2.
Marks  KJ , Whitaker  M , Anglin  O ,  et al; COVID-NET Surveillance Team.  Hospitalizations of children and adolescents with laboratory-confirmed COVID-19—COVID-NET, 14 states, July 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(7):271-278. doi:10.15585/mmwr.mm7107e4 PubMedGoogle ScholarCrossref
3.
Dawood  FS , Porucznik CA, Veguilla V,  et al. Incidence rates, household infection risk, and clinical characteristics of SARS-CoV-2 infection among children and adults in Utah and New York City, New York.  JAMA Pediatr. 2022;176(1):59-67.
4.
Lu  X , Zhang  L , Du  H ,  et al; Chinese Pediatric Novel Coronavirus Study Team.  SARS-CoV-2 infection in children.   N Engl J Med. 2020;382(17):1663-1665. doi:10.1056/NEJMc2005073 PubMedGoogle ScholarCrossref
5.
McLean  HQ , Grijalva  CG , Hanson  KE ,  et al.  Household transmission and clinical features of SARS-CoV-2 infections.   Pediatrics. 2022;149(3):e2021054178. doi:10.1542/peds.2021-054178 PubMedGoogle ScholarCrossref
6.
Chu  VT , Yousaf  AR , Chang  K ,  et al; Georgia Camp Investigation Team.  Household transmission of SARS-CoV-2 from children and adolescents.   N Engl J Med. 2021;385(10):954-956. doi:10.1056/NEJMc2031915 PubMedGoogle ScholarCrossref
7.
Larosa  E , Djuric  O , Cassinadri  M ,  et al; Reggio Emilia COVID-19 Working Group.  Secondary transmission of COVID-19 in preschool and school settings in northern Italy after their reopening in September 2020: a population-based study.   Euro Surveill. 2020;25(49):2001911. doi:10.2807/1560-7917.ES.2020.25.49.2001911 PubMedGoogle ScholarCrossref
8.
Bhuiyan  MU , Stiboy  E , Hassan  MZ ,  et al.  Epidemiology of COVID-19 infection in young children under five years: a systematic review and meta-analysis.   Vaccine. 2021;39(4):667-677. doi:10.1016/j.vaccine.2020.11.078 PubMedGoogle ScholarCrossref
9.
Siegel  DA , Reses  HE , Cool  AJ ,  et al; MAPW1.  Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0-17 years—United States, August 2020-August 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(36):1249-1254. doi:10.15585/mmwr.mm7036e1 PubMedGoogle ScholarCrossref
10.
Nachega  JB , Sam-Agudu  NA , Machekano  RN ,  et al; African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents.  Assessment of clinical outcomes among children and adolescents hospitalized with COVID-19 in 6 sub-Saharan African countries.   JAMA Pediatr. 2022;176(3):e216436. doi:10.1001/jamapediatrics.2021.6436 PubMedGoogle ScholarCrossref
11.
CDC COVID-19 Response Team.  SARS-CoV-2 B.1.1.529 (omicron) variant—United States, December 1-8, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(50):1731-1734. doi:10.15585/mmwr.mm7050e1 PubMedGoogle ScholarCrossref
12.
Harris  PA , Taylor  R , Thielke  R , Payne  J , Gonzalez  N , Conde  JG .  Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.   J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 PubMedGoogle ScholarCrossref
13.
Jahrsdörfer  B , Kroschel  J , Ludwig  C ,  et al.  Independent side-by-side validation and comparison of 4 serological platforms for SARS-CoV-2 antibody testing.   J Infect Dis. 2021;223(5):796-801. doi:10.1093/infdis/jiaa656 PubMedGoogle ScholarCrossref
14.
Thompson  MG , Burgess  JL , Naleway  AL ,  et al.  Prevention and attenuation of COVID-19 with the BNT162b2 and mRNA-1273 vaccines.   N Engl J Med. 2021;385(4):320-329. doi:10.1056/NEJMoa2107058 PubMedGoogle ScholarCrossref
15.
Centers for Disease Control and Prevention. People with certain medical conditions. Centers for Disease Control and Prevention; 2021. Accessed November 11, 2021. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html
16.
Kislaya  I , Rodrigues  EF , Borges  V ,  et al; PT-COVID-19 Group.  Comparative effectiveness of coronavirus vaccine in preventing breakthrough infections among vaccinated persons infected with Delta and alpha variants.   Emerg Infect Dis. 2022;28(2):331-337. doi:10.3201/eid2802.211789 PubMedGoogle ScholarCrossref
17.
Marc  A , Kerioui  M , Blanquart  F ,  et al.  Quantifying the relationship between SARS-CoV-2 viral load and infectiousness.   Elife. 2021;10:e69302. doi:10.7554/eLife.69302 PubMedGoogle ScholarCrossref
18.
Chung  E , Chow  EJ , Wilcox  NC ,  et al.  Comparison of symptoms and RNA levels in children and adults with SARS-CoV-2 infection in the community setting.   JAMA Pediatr. 2021;175(10):e212025. doi:10.1001/jamapediatrics.2021.2025 PubMedGoogle ScholarCrossref
19.
Kociolek  LK , Muller  WJ , Yee  R ,  et al. Comparison of upper respiratory viral load distributions in asymptomatic and symptomatic children diagnosed with SARS-CoV-2 infection in pediatric hospital testing programs.  J Clin Microbiol. 2020;59(1):e02593-20. doi:10.1128/JCM.02593-20 PubMedCrossref
20.
Han  MS , Seong  MW , Kim  N ,  et al.  Viral RNA load in mildly symptomatic and asymptomatic children with COVID-19, Seoul, South Korea.   Emerg Infect Dis. 2020;26(10):2497-2499. doi:10.3201/eid2610.202449 PubMedGoogle ScholarCrossref
21.
Lee  S , Kim  T , Lee  E ,  et al.  Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea.   JAMA Intern Med. 2020;180(11):1447-1452. doi:10.1001/jamainternmed.2020.3862 PubMedGoogle ScholarCrossref
22.
Han  MS , Byun  JH , Cho  Y , Rim  JH .  RT-PCR for SARS-CoV-2: quantitative versus qualitative.   Lancet Infect Dis. 2021;21(2):165. doi:10.1016/S1473-3099(20)30424-2 PubMedGoogle ScholarCrossref
23.
Salvatore  PP , Dawson  P , Wadhwa  A ,  et al.  Epidemiological correlates of polymerase chain reaction cycle threshold values in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).   Clin Infect Dis. 2021;72(11):e761-e767. doi:10.1093/cid/ciaa1469 PubMedGoogle ScholarCrossref
24.
Viner  RM , Ward JL, Hudson LD, et al.  Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents.   Arch Dis Child. 2021;106:802–807. doi:10.1136/archdischild-2020-320972 PubMedGoogle ScholarCrossref
25.
Teyssou  E , Delagrèverie  H , Visseaux  B ,  et al.  The delta SARS-CoV-2 variant has a higher viral load than the beta and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients.   J Infect. 2021;83(4):e1-e3. doi:10.1016/j.jinf.2021.08.027 PubMedGoogle ScholarCrossref
26.
Luo  CH , Morris  CP , Sachithanandham  J ,  et al.  Infection with the SARS-CoV-2 Delta variant is associated with higher recovery of infectious virus compared to the alpha variant in both unvaccinated and vaccinated individuals.   Clin Infect Dis. 2021;ciab986. doi:10.1093/cid/ciab986 PubMedGoogle ScholarCrossref
27.
Ong  SWX , Chiew  CJ , Ang  LW ,  et al.  Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (alpha), B.1.315 (beta), and B.1.617.2 (delta).   Clin Infect Dis. 2021;ciab721. doi:10.1093/cid/ciab721 PubMedGoogle ScholarCrossref
28.
Kissler  SM , Fauver  JR , Mack  C ,  et al.  Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated persons.   N Engl J Med. 2021;385(26):2489-2491. doi:10.1056/NEJMc2102507 PubMedGoogle ScholarCrossref
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close