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Immunisation and Vaccine Preventable Diseases Division, UKHSA, 61 Colindale Avenue, London, United KingdomStatistics Modelling and Economics Department, UKHSA, 61 Colindale Avenue, London, United KingdomSero-epidemiology Unit, UKHSA, Public Health Laboratory Manchester, Manchester Royal Infirmary, Oxford Road, Manchester, United KingdomUK Health Security Agency, Porton Down, Salisbury, United KingdomReference Laboratories, UKHSA, 61 Colindale Avenue, London, United Kingdom
We previously reported large increases in SARS-CoV-2 seropositivity in children in England due to the Delta wave since April 2021 and roll out of paediatric vaccination to 16–17 year-olds since August 2021 and 12–15 year-olds since September 2021.
Briefly, the UKHSA Sero-epidemiology Unit (SEU) coordinates the collection of residual samples from children aged 1–17 years having a blood test as part of their clinical management in 44 hospital trusts across seven National Health Service (NHS) regions (∼400 residual samples/month). Samples were processed using two serological assays; the Roche Elecsys assays for i) antibodies to the nucleocapsid (N) protein, informing on previous exposure to SARS-C0V-2 and ii) antibodies to the spike (S) protein receptor binding domain, detecting previous infection as well as vaccine-induced immune response.
From September 01 2021, to September 30 2022, 4873 paediatric sera (age groups 1–4 years n = 551; 5–11 years n = 1331; 12–15 years n = 2364; 16–17 years n = 627) were tested. The overall national prevalence estimate of seropositivity, weighted by age group and NHS region, based on results from the Roche S assay, increased from 48.5% (95% CrI 40.8%–55.1%) during September-October 2021 to 97.2% (95% CrI 93.7%–98.9%) by September 2022 (see Fig. 1, Fig. 2). For N-antibody positivity, the respective rates were 34% (27.5%–41.2%) and 86.7% (81.1%–91.6%).
During November-December 2021, S-antibody seropositivity was highest in 16–17 year-olds at 86.5% (78.7%–91.7%) and 12–15 year-olds at 78% (69.8%–83.5%), however a considerable proportion (46.6% and 24.3% respectively) tested S positive and N negative, largely indicating immune response to vaccination alone (a small proportion being due to faster waning and decreased sensitivity of the N antibody response). This is consistent with a vaccine uptake of at least 1 dose of 16.7% in 16–17 and < 1% in 12–15 year-olds, respectively, by September 2021.
Seropositivity decreased with age and was 36.9% (25.5%–49.7%) in 1–4 year olds with the majority of those testing S positive also testing N positive. With the emergence of the highly transmissible Omicron variant which was able to evade both natural and vaccine-induced immunity in November 2021, large increases in N-antibody seropositivity were observed in early 2022, consistent with widespread infection. N-antibody seropositivity increased across all childhood age-groups throughout 2022, reaching 93.3% (80.4%–98.6%) in children aged one to four years, to 98.6% (95.1%–99.8%) in those aged 16–17 years by September 2022. The difference in S and N seropositivity decreased to 7.3% in the oldest age group, close to that seen in the younger age groups (1–11 years). From April 2022, whilst acknowledging that most 5–11 year-olds had already been exposed to SARS-CoV-2, the UK Joint Committee for Vaccination and Immunisation (JCVI) recommended two doses of COVID-19 vaccine to this age group to ‘increase the immunity of vaccinated individuals against severe COVID-19 in advance of a potential future wave’.
Consistent with the low proportion of 5–11 year-olds who were only S-antibody positive (representing mostly vaccinated but uninfected children) by September 2022, national uptake of at least one dose of a COVID-19 vaccine in this age group was 10.7% compared to 50.1% in 12–15 year-olds and 64.1% in 16–17 year-olds.
Overall, our findings show large increases of SARS-CoV-2 antibody seropositivity in children following the emergence of the Omicron variant, resulting in high rates of primary infection in unvaccinated children and breakthrough infection in previously-vaccinated, mainly older children.
Consistent with these findings, a large nationally representative study using oral fluids in schools in England, estimated that 82.0% (95% CI: 80.3% to 83.5%) of 4–10 year-olds and 99.3% (95% CI: 98.9% to 99.6%) of 11–17 year-olds were sero-positive by March 2022 through a combination of infection and vaccination.
measures seroprevalence using two different S-antibody thresholds to distinguish between response to natural infection (179 ng/ml, equivalent to 100 BAU/ ml) and vaccination (800 ng/ml, equivalent to 447 BAU/ml).
When applying the same threshold of ≥100 BAU to our samples for the period July to September 2022, seropositivity rates in our cohort were similar; 69.9% (60.4% - 79.8%) of 5–11 year-olds and 92% (87.7% - 95.1%) of 12–15 year-olds (see Table 1).
Table 1Population weighted seropositivity estimates of residual paediatric samples using the Roche S assays by age group collected July-September 2022 applying manufacturer recommended threshold of ≥ 1BAU/ml and ≥100 BAU, equivalent to 179 ng/ml used in the ONS survey.
modelled population weighted% positive (95% CrI) ≥ 1BAU/ml
modelled population weighted% ≥ 100 BAU/ml (95% CrI)
however similar findings from the ONS household survey show that sero-surveillance using SEU samples is a valid, cost-effective and important source to monitor seroprevalence in children.
A growing number of post-implementation studies have reported significant albeit short-term protection against SARS-CoV-2 infection as well as protection against hospitalisation for COVID-19 in vaccinated compared to unvaccinated, previously uninfected children.
More recent studies have shown significant protection after primary SARS-CoV-2 infection against reinfection as well as hospitalisation for severe COVID-19, especially after primary omicron infection, with potentially longer protection in previously-infected, vaccinated children.
In conclusion, in currently the most up-to-date seroprevalence study following multiple omicron waves in England, we estimate that nearly all children aged 1–17 years have been exposed to SARS-CoV-2 irrespective of vaccination status. Our findings have implications for future recommendations for childhood COVID-19 vaccination.
We would like to thank the hospitals listed below for their support throughout the pandemic making this surveillance possible: Alder Hey Children...s NHS Foundation Trust, Royal Devon and Exeter NHS Foundation Trust, University Hospitals Leicester NHS Trust, Sheffield Children's NHS Foundation Trust, The Rotherham NHS Foundation Trust, Barnsley Hospital NHS Foundation Trust, Mid Yorkshire Hospitals NHS Trust, Northwick Park Hospital, Warrington and Halton Teaching Hospitals NHS Foundation Trust, Manchester University NHS Foundation Trust, Homerton University Hospital NHS Foundation Trust, Bolton NHS Foundation Trust, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Salford Royal NHS Foundation Trust, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, York and Scarborough Teaching Hospitals NHS Foundation, Lancashire Teaching Hospitals; North Tyneside General Hospital, The Royal Wolverhampton NHS Trust, University Hospitals Sussex NHS trust; Stockport NHS Foundation Trust, North West Anglia NHS Foundation Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust.
Large increases in SARS-CoV-2 seropositivity in children in England: effects of the delta wave and vaccination.