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. 2023 Oct 1;177(10):1073-1084.
doi: 10.1001/jamapediatrics.2023.3117.

International Pediatric COVID-19 Severity Over the Course of the Pandemic

Yanshan Zhu  1   2 , Flávia Jacqueline Almeida  3   4 , J Kenneth Baillie  5   6   7   8 , Asha C Bowen  9 , Philip N Britton  10   11 , Martin Eduardo Brizuela  12 , Danilo Buonsenso  13 , David Burgner  14   15   16 , Keng Yih Chew  1 , Kulkanya Chokephaibulkit  17 , Cheryl Cohen  18   19 , Stephania A Cormier  20   21 , Nigel Crawford  14   16 , Nigel Curtis  14   15   22 , Camila G A Farias  4 , Charles F Gilks  23 , Anne von Gottberg  18   24 , Diana Hamer  25 , Daniel Jarovsky  3   4 , Waasila Jassat  26 , Ana Rita Jesus  27 , Lisa S Kemp  25 , Benjawan Khumcha  17 , Georgina McCallum  1 , Jessica E Miller  14   15 , Rosa Morello  13 , Alasdair P S Munro  28   29 , Peter J M Openshaw  30   31 , Srivatsan Padmanabhan  32   33 , Wanatpreeya Phongsamart  17 , Gary Reubenson  34 , Nicole Ritz  15   35   36 , Fernanda Rodrigues  27   37 , Supattra Rungmaitree  17 , Fiona Russell  14   15 , Marco A P Sáfadi  3   4 , Christoph Saner  38   39   40 , Malcolm G Semple  41   42 , Daniella Gregória Bomfim Prado da Silva  4 , Laíse Marine Moura de Sousa  3 , Marília Diogo Moço Souza  3 , Kirsten Spann  43 , Sibongile Walaza  18   19 , Nicole Wolter  18   24 , Yao Xia  44 , Daniel K Yeoh  45 , Heather J Zar  46 , Petra Zimmermann  47 , Kirsty R Short  1   48 ; International Severe Acute Respiratory and Emerging Infection Consortium Comprehensive Clinical Characterisation Collaboration (ISARIC4C) investigatorsPediatric Active Enhanced Disease Surveillance (PAEDS) Network group
Collaborators, Affiliations

International Pediatric COVID-19 Severity Over the Course of the Pandemic

Yanshan Zhu et al. JAMA Pediatr. .

Erratum in

  • Errors in Article.
    [No authors listed] [No authors listed] JAMA Pediatr. 2024 Jan 1;178(1):99. doi: 10.1001/jamapediatrics.2023.5198. JAMA Pediatr. 2024. PMID: 37930672 Free PMC article. No abstract available.

Abstract

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear.

Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children.

Design, setting, and participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded.

Exposures: SARS-CoV-2 hospitalization during the stipulated time frame.

Main outcomes and measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy.

Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children.

Conclusions and relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Britton reported grants from Australian Commonwealth Department of Health and Aged Care PAEDS and the Royal Australasian College of Physicians Cottrell Research Establishment Fellowship during the conduct of the study. Dr Buonsenso reported personal fees from Pfizer during the conduct of the study. Dr Burgner reported grants from the National Health and Medical Research Council during the conduct of the study. Dr Cohen reported grants from US Centers for Disease Control and Prevention during the conduct of the study and grants from PATH, the South African Medical Research Council, and the Bill & Melinda Gates Foundation outside the submitted work. Dr Cormier reported grants from the National Institutes of Health (P42 ES013648) during the conduct of the study. Dr Crawford reported grants from the Royal Columbian Hospital Foundation and the Victorian State Government of Australia during the conduct of the study. Dr von Gottberg reported grants from the US Centers for Disease Control and Prevention, the World Health Organization, Africa Region, the US Centers for Disease Control and Prevention through African Field Epidemiology Network, Africa Centres for Disease Control and Prevention (Institute of Pathogen Genomics), Fleming Fund SeqAfrica, and African Medical Research Council during the conduct of the study. Dr Openshaw reported advisory board fees from GSK, Janssen, Seqirus, and Moderna outside the submitted work. Dr Rodrigues reported honoraria for participation in advisory boards and as speaker in scientific meetings from Pfizer, Merck, Sharp & Dohme, GSK, and Sanofi outside the submitted work. Dr Sáfadi reported grants and personal fees from Pfizer, Sanofi, and Abbott, and grants from GSK outside the submitted work. Dr Semple reported grants from the National Institute of Health Research UK, Medical Research Council UK, the Health Protection Research Unit in Emerging & Zoonotic Infections, and the University of Liverpool and UK Health Security Agency during the conduct of the study, nonfinancial support from Chiesi Farmaceutici S.p.A., being minority shareholder of Integrum Scientific, being an independent external and nonremunerated member of Pfizer’s External Data Monitoring Committee for their mRNA vaccine program, and being a member of HMG UK Scientific Advisory Group for Emergencies, COVID-19 Response from March 2020 to March 2022 outside the submitted work. Dr Walaza reported grants from the US Centers for Disease Control and Prevention, the National Department of Health, and the Bill and Melinda Gates Foundation outside the submitted work. Dr Wolter reported grants from US Centers for Disease Control and Prevention, the Bill and Melinda Gates Foundation, and Sanofi outside the submitted work. Dr Zimmermann reported grants from the Federal Office of Public Health Switzerland during the conduct of the study. Dr Short reported consulting fees from Sanofi, Novonodisk, and Roche outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Meta-Analysis Risk Ratios (RRs) for Intensive Care Unit Admission, Noninvasive/Invasive Mechanical Ventilatory Support, and Oxygen Therapy Among Pediatric Patients Younger Than 6 Months Old
Models were adjusted for sex (male/female), preexisting cardiovascular disease (yes/no), asthma (yes/no), neurological disorder (yes/no), childhood cancer (yes/no), immunological disease or immunosuppression (yes/no), diabetes (yes/no), HIV positive (yes/no), tuberculosis (yes/no), and prematurity (less than 37 weeks’ gestation [yes/no]) as appropriate. South Africa site 1 data were obtained from South Africa DATCOV and South Africa site 2 data were obtained from the National Institute for Communicable Diseases of South Africa. Data from the US (time frame 3 [T3]), Thailand (time frame 1 [T1]), and Australia (T1) were not included in this model because data were not available. NA indicates not applicable; T2, time frame 2.
Figure 2.
Figure 2.. Meta-Analysis Risk Ratios (RRs) for Intensive Care Unit Admission, Noninvasive/Invasive Mechanical Ventilatory Support, and Oxygen Therapy Among Pediatric Patients Aged 6 Months to Younger Than 5 Years
Models were adjusted for sex (male/female), preexisting cardiovascular disease (yes/no), asthma (yes/no), neurological disorder (yes/no), childhood cancer (yes/no), immunological disease or immunosuppression (yes/no), diabetes (yes/no), HIV positive (yes/no), tuberculosis (yes/no), and prematurity (less than 37 weeks’ gestation [yes/no]) as appropriate. South Africa site 1 data were obtained from South Africa DATCOV and South Africa site 2 data were obtained from the National Institute for Communicable Diseases of South Africa. Data from the US (time frame 3 [T3]), Thailand (time frame 1 [T1]), and Australia (T1) were not included in this model because data were not available. NA indicates not applicable; T2, time frame 2.
Figure 3.
Figure 3.. Meta-Analysis Risk Ratios (RRs) for Intensive Care Unit Admission, Noninvasive/Invasive Mechanical Ventilatory Support, and Oxygen Therapy Among Pediatric Patients Aged 5 to Younger Than 18 Years
Models were adjusted for sex (male/female), preexisting cardiovascular disease (yes/no), asthma (yes/no), neurological disorder (yes/no), childhood cancer (yes/no), immunological disease or immunosuppression (yes/no), diabetes (yes/no), HIV positive (yes/no), tuberculosis (yes/no), and prematurity (less than 37 weeks’ gestation [yes/no]), as appropriate. South Africa site 1 data were from South Africa DATCOV and South Africa site 2 data were from the National Institute for Communicable Diseases of South Africa. Data from the US (time frame 3 [T3]), Thailand (time frame 1 [T1]), and Australia (T1) were not included in this model because data were not available. NA indicates not applicable; T2, time frame 2.
Figure 4.
Figure 4.. Meta-Analysis Risk Ratios (RRs) for Intensive Care Unit Admission, Noninvasive/Invasive Mechanical Ventilatory Support, and Oxygen Therapy Among Pediatric Patients Aged 5 to Younger Than 18 Years Without COVID-19 Vaccination
Models were adjusted for sex (male/female), preexisting cardiovascular disease (yes/no), asthma (yes/no), neurological disorder (yes/no), childhood cancer (yes/no), immunological disease or immunosuppression (yes/no), diabetes (yes/no), HIV positive (yes/no), tuberculosis (yes/no), and prematurity (less than 37 weeks’ gestation [yes/no]), as appropriate. South Africa site 1 data were obtained from South Africa DATCOV and South Africa site 2 (SA_2) data were obtained from the National Institute for Communicable Diseases of South Africa. Data from the US (time frame 3 [T3]), Thailand (time frame 1 [T1]), and Australia (T1) were not included in this model because data were not available. NA indicates not applicable; T2, time frame 2.
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