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Significantly lower infection fatality rates associated with SARS-CoV-2 Omicron (B.1.1.529) infection in children and young people: active, prospective national surveillance, January-March 2022, England

  • Erjola Hani
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom
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  • Marta Bertran
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom
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  • Annabel Powell
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom
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  • Hannah Williams
    Affiliations
    Joint Modelling Team (JMT), UK Health Security Agency, UK

    Emergency Preparedness, Response and Resilience, UK Health Security Agency, Porton Down, SP4 0JG, UK
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  • Paul Birrell
    Affiliations
    Joint Modelling Team (JMT), UK Health Security Agency, UK

    MRC Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Cambridge Institute of Public Health, Cambridge, United Kingdom

    Statistical Modelling and Economics, UK Health Security Agency, Colindale, United Kingdom
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  • Daniela DeAngelis
    Affiliations
    MRC Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Cambridge Institute of Public Health, Cambridge, United Kingdom
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  • Mary E Ramsay
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom
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  • Author Footnotes
    ⁎ joint senior authors
    Godwin Oligbu
    Footnotes
    ⁎ joint senior authors
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom

    Paediatric Infectious Diseases Research Group, St George's University of London, London, United Kingdom
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  • Author Footnotes
    ⁎ joint senior authors
    Shamez N Ladhani
    Correspondence
    Corresponding author: 02083277155; 61 Colindale Ave, London NW9 5EQ
    Footnotes
    ⁎ joint senior authors
    Affiliations
    Immunisation and Vaccine-Preventable Diseases Division, UK Health Security Agency, London, United Kingdom

    Paediatric Infectious Diseases Research Group, St George's University of London, London, United Kingdom
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  • Author Footnotes
    ⁎ joint senior authors
Published:January 23, 2023DOI:https://doi.org/10.1016/j.jinf.2023.01.032

      Highlights

      • Children and young people (CYP) have a low risk of severe or fatal COVID-19
      • The Omicron wave since late 2021 was associated with very infection rates in CYP
      • The infection fatality rate following Omicron infection was 1 per million infections
      • Infection fatality rate was 10-fold lower with Omicron than the first pandemic wave
      • Most deaths occurred in CYP with sever comorbidities, especially neurodisabilities
      Children, and young people (CYP) have a very low risk of severe or fatal COVID-19, especially when compared to adults.(
      • Ludvigsson JF.
      Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
      ) The recent UK seroprevalence study published in the Journal of Infection, reported that, by September 2022, 86.7% of children aged 1-17 years had been exposed to SARS-CoV-2, based on SARS-CoV-2 nucleocapsid (N) protein, mainly after the SARS-CoV-2 Omicron variant wave.(
      • Oeser C
      • Whitaker H
      • Borrow R
      • Linley E
      • Tonge S
      • Rowe C
      • et al.
      Following the Omicron wave, the majority of children in England have evidence of previous COVID infection.
      ) The large number of Omicron infections reported in children, who were mainly unvaccinated at the time, raised concerns about increased hospitalisation and deaths in CYP.
      In England, UKHSA has been conducting COVID-19 surveillance in CYP since the start of the pandemic. We previously reported fatalities within 100 days of a positive SARS-CoV-2 test in CYP aged <20 years until the end of December 2021, which included the wild-type, alpha and delta variant waves in England. (
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Detailed follow-up identified 185 deaths within 100 days of a positive SARS-CoV-2 test and 81 (43.8%) were due to COVID-19, with 91% of deaths occurring within 30 days of testing, mainly in CYP with severe and/or life-limiting underlying conditions.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) We have now extended our previous analysis to explore cases and deaths in CYP during the first Omicron (BA1/BA.2) variant wave in England, where we found very low infection fatality rates despite higher numbers of infections.(
      • Nyberg T
      • Ferguson NM
      • Nash SG
      • Webster HH
      • Flaxman S
      • Andrews N
      • et al.
      Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
      )
      Our surveillance methodology has been reported previously.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Confirmed COVID-19 cases in CYP aged <20 years during January-March 2022 were linked to electronic vaccination records, Hospital Episode Statistics (HES) and Personal Demographic Service (PDS) to identify fatalities within 30 days of testing. We used multiple data sources to ascertain cause of death, including surveillance questionnaires sent to GPs, hospital discharge summaries, post-mortem reports, and death registration records. Any sudden/unexpected deaths where no other cause was identified was attributed to COVID-19. Age-specific infection fatality rates (IFR) were calculated using estimated, rather than confirmed, national SARS-CoV-2 infections from PHE- Cambridge real-time modelling,(
      • Birrell P
      • Blake J
      • van Leeuwen E
      • Gent N
      • De Angelis D.
      Real-time nowcasting and forecasting of COVID-19 dynamics in England: the first wave.
      ) as confirmed infections underestimated infection rates by up to four-fold.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Published Office of National Statistics mid-year population estimates,(

      Office of National Statistics. Estimates of the population for the UK, England and Wales, Scotland and Northern Ireland. [Mid-2020]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/populationestimatesforukenglandandwalesscotlandandnorthernireland (accessed 18 January 2023).

      ) and all-cause deaths,(

      Office for National Statistics. Deaths registered weekly in England and Wales, provisional (November 2022). Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/weeklyprovisionalfiguresondeathsregisteredinenglandandwales (accessed 18 January 2023).

      ) were used to calculate mortality rates.
      During January-March 2022, there were 879,944 positive SARS-CoV-2 infections and 46 deaths within 30 days of a positive test, including 11 due to COVID-19 (Figure 1). All followed primary SARS-CoV-2 infection, seven (66%) were male, six were White (55%) and eight (73%) had underlying comorbidities, including four with severe neurodisabilities (Supplement 1). Ten were hospitalised, with three requiring intensive care, while one case was diagnosed post-mortem. The median interval between testing and death was one (IQR 0-7) day. Of the eight CYP who were ≥12-years and eligible for vaccination, including six with underlying conditions, five had received two doses, one had one dose and two were unvaccinated.
      Fig 1
      Fig 1COVID-19 infection rates by age group and number of deaths by cause of death in CYP <20 years (predominant circulating variant shown by coloured chevrons)
      There were 7,175,612 estimated infections in <20-year-olds (IFR, 0.1/100,000 vs 0.7/100,000 during March 2020 to December 2021): there were no fatalities in <1year-olds (0.0 vs 0.7/100,000), 2 in 1-4-year-olds (0.2 vs 0.3/100,000), 1 in 5-11-year-olds (0.1 vs 0.3/100,000), 2 in 12-15-year-olds (0.1 vs 0.9/100,000) and 6 in 16-19-year-olds (0.4 vs 1.5/100,000) (
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ). COVID-19 contributed to 1.0% (10/1,003) of deaths in <20-year-olds during January-March 2022, compared to 1.2% during March 2020 to December 2021.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) IFR during the Omicron wave was lower the first pandemic wave (1.0/100,000; 21/2,062,780), alpha (0.8/ 100,000; 15/1,980,140) and delta (0.7/100,000; 81/11,629,407) waves.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      )
      Despite very large infections during Omicron wave compared to previous waves, there were eleven COVID-19 deaths in CYP in England, equivalent to 3.7 monthly fatalities, which was no different to the 81 deaths during the previous 22 months.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Consequently, IFR during the omicron wave was 10-fold, 8-fold, and 6-fold lower than the wild type, alpha and delta waves, respectively.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Most fatalities involved CYP with severe comorbidities, especially neurodisabilities, similar to previous variant waves.(
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) Some deaths occurred despite vaccination against COVID-19. In England, we have previously reported less severe disease across all age groups with omicron compared to delta, in terms of hospital attendance, hospitalizations and death (
      • Nyberg T
      • Ferguson NM
      • Nash SG
      • Webster HH
      • Flaxman S
      • Andrews N
      • et al.
      Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
      ), which is consistent with a recent US study (
      • Lewnard JA
      • Hong VX
      • Patel MM
      • Kahn R
      • Lipsitch M
      • Tartof SY.
      Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California.
      ). In CYP there were too few fatalities to assess differences between the two variants (
      • Nyberg T
      • Ferguson NM
      • Nash SG
      • Webster HH
      • Flaxman S
      • Andrews N
      • et al.
      Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study.
      ,
      • Lewnard JA
      • Hong VX
      • Patel MM
      • Kahn R
      • Lipsitch M
      • Tartof SY.
      Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California.
      ). One study from Qatar specifically focussed on CYP aged <18 years and found that primary infection with omicron was associated with an 88% (95% CI, 82-93%) lower odds of moderate or severe/critical disease compared to delta, with severe Omicron disproportionately affecting CYP with underlying comorbidities (aOR 3.16; 95% CI 1.11-9.00) (
      • Butt AA
      • Dargham SR
      • Loka S
      • Shaik RM
      • Chemaitelly H
      • Tang P
      • et al.
      Coronavirus Disease 2019 Disease Severity in Children Infected With the Omicron Variant.
      ). In the US, too, the risk of severe disease was significantly lower with omicron than delta in under 5 year olds (
      • Wang L
      • Berger NA
      • Kaelber DC
      • Davis PB
      • Volkow ND
      • Xu R.
      Incidence Rates and Clinical Outcomes of SARS-CoV-2 Infection With the Omicron and Delta Variants in Children Younger Than 5 Years in the US.
      ).The lower risk of severe disease and fatalities is reassuring given the higher numbers of childhood hospitalisations during the omicron wave in England (
      • Bertran M
      • Amin-Chowdhury Z
      • Davies HG
      • Allen H
      • Clare T
      • Davison C
      • et al.
      COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.
      ) and elsewhere (
      • Bahl A
      • Mielke N
      • Johnson S
      • Desai A
      • Qu L.
      Severe COVID-19 outcomes in pediatrics: An observational cohort analysis comparing Alpha, Delta, and Omicron variants.
      ). Potential reasons for lower severity of omicron infections include a predilection for upper rather than lower airway infection as well as protection from prior infection and vaccination.(
      • Sigal A.
      Milder disease with Omicron: is it the virus or the pre-existing immunity?.
      )
      In conclusion, we estimate the risk of death due to COVID-19 to be one in a million omicron infections in CYP, being at least 6-fold lower than the preceding waves. With increasing immunity from prior infection and vaccination, IFR is likely to drop further. Most COVID-19 fatalities occurred in CYP with severe/life-limiting comorbidities. This has important policy implications for COVID-19 vaccination and booster recommendations for CYP.

      Declaration of Competing Interest

      none

      Funding

      none

      Acknowledgments

      We thank Natalie Mensah and Rashmi Malkani for case follow-up and administrative support. We thank all the general practitioners, hospital clinicians, healthcare professionals, coroners, and administrative staff within the NHS and Coroners’ offices for completing questionnaires and providing additional information where needed. We also thank the UKHSA COVID-19 Epidemiology Cell for monitoring fatalities in CYP with confirmed SARS-CoV-2 infections.

      Appendix. Supplementary materials

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