Following the Omicron wave, the majority of children in England have evidence of previous COVID infection

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 2021.¹ The emergence of the Omicron variant in November 2021 along with multiple subvariant waves thereafter has resulted in high rates of infection across all age groups, particularly in young children.² Additionally, the UK recommended non-urgent COVID-19 vaccination for 5–11 year-olds from April 2022.³ Here, we describe the changes in SARS-CoV-2 seroprevalence rates in children during September 2021 to September 2022 in England.

Our serosurveillance methodology has been described previously.¹ 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.⁴ Statistical methods were described previously.¹

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%).

Fig. 1.

Population weighted seropositivity estimates of residual paediatric samples by period and age group collected from 1st September 2021 to 30th September 2022, using the Roche N and S assays.

Fig. 2.

Population weighted seropositivity estimates of residual paediatric samples by period and age group collected from 1st September 2021 to 30th September 2022, using the Roche N and S assays, stacked columns represent the proportion of samples testing positive with both assays (yellow) and the proportion testing positive with Roche S only (blue).

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 2021.⁵

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’.³ 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.⁵

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.⁶

A national household survey by the Office of National Statistics (ONS)⁷ 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).⁸ By the end of September 2022, this survey estimated that 74.2% of 8–11 year-olds and 93.0% of 12–15 year-olds had antibody levels ≥ 179 ng/ml.⁷

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 1.

Population 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.

	pos	total	modelled population weighted% positive (95% CrI) ≥ 1BAU/ml	≥100	total	modelled population weighted% ≥ 100 BAU/ml (95% CrI)
Overall	658	669	97.2% (93.7% - 98.9%)	553	669	74.6% (67.6% - 82.3%)
age 1–4	30	34	93.3% (80.4% - 98.6%)	18	34	56.5% (38.5% - 73.7%)
age 5–11	192	196	98.1% (95.1% - 99.4%)	130	196	69.9% (60.4% - 79.8%)
age 12–15	349	351	99.2% (97.8% - 99.8%)	321	351	92% (87.7% - 95.1%)
age 16–17	87	88	98.6% (95.1% - 99.8%)	84	88	95.6% (90% - 98.5%)

Limitations of our study include the small sample size and the use of residual sera taken from children attending healthcare settings, potentially limiting the representativeness of our cohort,¹ 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.⁹ 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.¹⁰ Such data are critical for making decisions on COVID-19 vaccination and boosting in countries where nearly all children have been exposed to SARS-CoV-2 at least once.⁹

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.