Large increases in SARS-CoV-2 seropositivity in children in England: Effects of the delta wave and vaccination.

Recently, Whitaker et al. reported changes in SARS-CoV-2 seroprevalence in adults after introduction of a vaccination programme. Here we describe the impact of the delta wave and initiation of vaccination on seroprevalence in children. Sero-epidemiological surveys are important to monitor temporal and geographical distribution of SARS-CoV-2 and provide information on asymptomatic infections. Age-stratified surveys enable monitoring of prevalence estimates in different age groups and their contribution to transmission.

The UK Health Security Agency (UKHSA, formerly PHE) along with NHS partners and academic collaborators implemented a range of national sero-surveillance programmes to monitor antibody prevalence to COVID-19 in children and young adults, which included expansion of existing collections. Here we present results from residual serum samples collected from children aged one to 17 years in England from September 2020 to October 2021.

The UKHSA Sero-epidemiology Unit (SEU) coordinates a national collection across seven NHS regions of residual serum samples from routine microbiological testing which was enhanced at the start of the pandemic to increase sample numbers and geographic representation. Overall, a total of 26 hospital trusts have participated in the main SEU collection since the start of the pandemic with an average of 200 samples from children aged one to 17 years tested each month. In addition, a targeted paediatric collection from 18 hospitals across England providing paediatric services was established, with approximately 500 paediatric samples collected each month. Demographical data collected include age, sex and geographical region. The SEU has ethical approval for collection of anonymised samples for serosurveys of diseases for which a vaccine exists or is in active development (05/Q0505/45).

Samples were tested using two serological assays. The Roche Elecsys assay was used for detection of high avidity total antibody to SARS-CoV-2 nucleocapsid (N) protein, which informs on previous exposure to SARS-CoV-2. Sensitivity and specificity are 83.9% (95% CI 74.8–90.7) and 100% (95% CI 99.1–100), respectively in samples collected within 12 weeks of onset. The Roche Elecsys assay was used to detect antibodies to SARS-CoV-2 spike (S) protein receptor binding domain with a sensitivity of 95.5% (95%CI 93.2–97.1) and specificity of 100% (95% CI 99.1–100). This assay detects previous infection as well as vaccine induced immune response. As waning with assays based on S antibody detection are less pronounced than for N-based assays, analyses are focused on results from the S assay.

Bayesian multilevel regression and poststratification (MRP) models were used to estimate seropositivity, with poststratification by age group and NHS region based on Office for National Statistics population estimates. Analyses were carried using RStan within R.

From 1st September 2020 to 31st October 2021, 5209 paediatric sera (age groups 1–4 years, n = 945; 5–11 years, n = 1525; 12–15 years, n = 2033; 16–17 years, n = 706) were obtained from the SEU and targeted paediatric collections.

The overall national prevalence estimate of seropositivity, weighted by age group and NHS region based on results from the Roche S assay, increased from 7.6% (95% CrI 3.2–18.2%) for the period September to October 2020 to 31.5% (25.3%–39.1%) in March and April 2021, and, after remaining stable over summer, increased to 46.1% (38.3–53.6%) in October 2021 (Fig. 1 and Table 1 ).

Fig. 1.

Population weighted seropositivity estimates (posterior median) of residual samples from the SEU and paediatric collections by period and age group, obtained from September 2020 to October 2021 using the Roche S and N assay. Stacked columns represent the proportion of samples testing positive with both assays (yellow) and the proportion testing positive with the Roche S, but negative with Roche N (blue).

Table 1

Population weighted seropositivity estimates (posterior median with 95% credible interval) of residual SEU and paediatric collections samples collected September 2020 to October 2021 using the Roche S and N assays.

		Roche S			Roche N
Period	Age, region	Pos	Total	Population weighted% pos (95% CI)	Pos	Total	Population weighted% pos (95% CI)
Sept-Oct 2020	All	8	119	7.6% (3.2% - 18.2%)	6	120	6.3% (2.2% - 17%)
	1–4	0	26	5.1% (0.4% - 16.4%)	0	26	4.5% (0.4% - 15.7%)
	5–11	3	42	7.5% (2.4% - 20.5%)	3	43	6.7% (2% - 20.3%)
	12–15	4	35	9.5% (3.3% - 25.5%)	2	35	6.1% (1.6% - 19.2%)
	16–17	1	16	7% (1.4% - 21.8%)	1	16	6% (1.3% - 20.4%)
	Lon	3	14	10.7% (3.3% - 32.4%)	3	14	10.5% (2.5% - 33.2%)
	NE	2	63	4.3% (1% - 10.2%)	1	64	2.7% (0.4% - 8%)
	NW	3	27	8.1% (2.7% - 20%)	2	27	5.6% (1.4% - 15.9%)
	SW	0	13	4.6% (0.3% - 14.6%)	0	13	3.3% (0.2% - 12.9%)
Nov-Dec 2020	All	94	711	14.8% (11.2% - 19.8%)	90	712	14.1% (10.6% - 19%)
	1–4	13	124	13% (7.6% - 19.2%)	11	124	11.7% (6.3% - 18%)
	5–11	42	259	16.2% (11.7% - 22.8%)	40	260	15.6% (11.2% - 22.1%)
	12–15	25	225	13.4% (9% - 19.1%)	25	225	13.1% (8.8% - 18.8%)
	16–17	14	103	15.5% (10.2% - 24.4%)	14	103	15.3% (9.9% - 24.4%)
	Lon	20	61	30.3% (19.8% - 42.6%)	20	61	30.3% (19.8% - 42.5%)
	Mid	3	20	13.3% (4.6% - 28.9%)	3	20	12.9% (4.3% - 28.6%)
	NE	30	206	14.5% (10.2% - 19.6%)	28	206	13.5% (9.4% - 18.5%)
	NW	32	199	15.6% (11.2% - 21%)	31	200	15% (10.6% - 20.2%)
	SW	3	35	9.2% (3.2% - 19.6%)	2	35	7% (1.9% - 16.5%)
Jan-Feb 2021	All	201	970	23.3% (18.4% - 29.5%)	182	975	22.1% (17.3% - 28.3%)
	1–4	32	190	22.2% (15.5% - 29.3%)	31	190	21.8% (15.6% - 28.7%)
	5–11	68	340	22.6% (17.1% - 29.4%)	62	341	21.6% (16.3% - 28.3%)
	12–15	70	298	25.2% (19.4% - 32.6%)	61	300	23% (17.6% - 30.2%)
	16–17	31	142	24.5% (18.3% - 32.6%)	28	144	22.8% (17% - 30.5%)
	Lon	32	88	34% (24.7% - 44.3%)	31	90	32.6% (23.6% - 42.7%)
	Mid	10	22	39.4% (21.8% - 59.6%)	10	22	39.5% (21.9% - 59.7%)
	NE	74	412	17.7% (14.3% - 21.6%)	67	413	16.1% (12.8% - 19.8%)
	NW	75	288	25.6% (20.9% - 30.8%)	66	288	22.6% (18.1% - 27.7%)
	SW	2	66	4.8% (1.3% - 11.3%)	2	68	4.5% (1.2% - 10.8%)
Mar-Apr 2021	All	288	925	31.5% (25.3% - 39.1%)	244	930	25.7% (20.1% - 33%)
	1–4	53	178	31.9% (24.3% - 40.6%)	43	179	25.4% (18.5% - 33.8%)
	5–11	87	315	29.7% (22.6% - 37.9%)	78	316	25% (18.7% - 32.8%)
	12–15	107	329	33.6% (26.4% - 42.3%)	97	331	28.3% (21.4% - 37.1%)
	16–17	41	103	33.5% (25.5% - 43.8%)	26	104	24.1% (16.4% - 32.7%)
	Lon	41	102	38% (29% - 47.7%)	35	102	33% (24.5% - 42.6%)
	Mid	9	20	39.4% (22.9% - 59.5%)	8	21	32.9% (17.8% - 52.6%)
	NE	114	489	23.1% (19.4% - 27%)	103	492	20.3% (16.9% - 24.1%)
	NW	118	267	43.3% (37.4% - 49.2%)	95	267	34.9% (29.4% - 40.7%)
	SW	4	35	15.9% (6.5% - 29%)	2	36	10.1% (2.8% - 22.2%)
May-Jun 2021	All	328	1186	27.5% (20.7% - 37.2%)	281	1187	21.8% (16.1% - 31.1%)
	1–4	43	196	24.3% (16.3% - 34.9%)	39	196	20.3% (13.6% - 30.1%)
	5–11	76	284	27.5% (19.9% - 37.9%)	63	284	21.4% (15.1% - 31.3%)
	12–15	152	537	29.4% (22% - 39.7%)	141	538	24.4% (17.7% - 34.7%)
	16–17	57	169	30.5% (22.1% - 42.2%)	38	169	21.3% (14.6% - 31.5%)
	Lon	96	211	42.6% (35.6% - 49.9%)	80	211	36.1% (29.6% - 43.1%)
	Mid	5	16	27.5% (12.4% - 48.7%)	3	16	17.4% (6% - 36.2%)
	NE	125	511	23.8% (20% - 27.9%)	120	512	22% (18.3% - 26.1%)
	NW	87	276	31.2% (25.9% - 36.9%)	69	276	24.7% (19.8% - 30.1%)
	SW	15	171	9% (5.4% - 13.9%)	9	171	5.8% (3% - 10%)
Jul-Aug 2021	All	202	685	26.4% (20.1% - 35.3%)	176	685	22.2% (16.5% - 31.4%)
	1–4	29	138	24.7% (16.8% - 34.9%)	24	138	20.5% (13.3% - 30.6%)
	5–11	39	167	24.2% (16.7% - 34.1%)	36	167	21% (14.3% - 30.9%)
	12–15	98	293	31.2% (23.1% - 41.8%)	89	293	26.6% (19% - 37.5%)
	16–17	36	87	29.2% (20.4% - 41.2%)	27	87	22.1% (14.6% - 33%)
	Lon	81	161	45.7% (37.1% - 54.4%)	72	161	41.4% (33.2% - 49.9%)
	Mid	35	111	30% (22.1% - 38.8%)	24	111	20.8% (14.1% - 28.9%)
	NE	80	354	21.3% (17.1% - 26%)	76	354	20% (15.9% - 24.6%)
	NW	3	12	24.3% (8.7% - 47.6%)	3	12	22.5% (7.5% - 46.6%)
	SW	3	45	8.6% (2.8% - 18.6%)	1	45	4.7% (0.9% - 13.3%)
Sep-Oct 2021	All	327	600	46.1% (38.3% - 53.6%)	239	600	33.5% (26.8% - 40.9%)
	1–4	42	92	41.5% (30.2% - 53.6%)	30	92	31.1% (21.7% - 41.9%)
	5–11	37	114	33.3% (24% - 44.1%)	29	114	26.7% (18.3% - 36.8%)
	12–15	182	311	59% (48.9% - 67.5%)	152	311	46.9% (37.5% - 56%)
	16–17	66	83	80.3% (69.2% - 88.4%)	28	83	36.9% (26.5% - 48.9%)
	Lon	39	63	43.3% (31.8% - 55.4%)	31	63	40.2% (29.3% - 52.8%)
	Mid	52	87	55% (45.3% - 65.1%)	34	87	36.6% (27.7% - 46.5%)
	NE	159	316	44.1% (38.2% - 50.2%)	135	316	34.4% (28.6% - 40.8%)
	NW	37	55	59.5% (47% - 72.1%)	25	55	39.4% (28.5% - 52%)
	SW	39	76	34.9% (24.7% - 46.9%)	14	76	18.2% (10.4% - 29%)

Roche S seropositivity varies by age with higher seropositivity persisting in children aged above 12 years at 59% (48.9–67.5%) for 12 to 15 year olds and 80.3% (69.2–88.4%) in those aged 16 to 17 in October.

Estimates based on the Roche N assay were largely comparable to results from the S assay from September to February 2021. However thereafter, N-based estimates were overall lower, with more pronounced increases of S-based estimates, particularly in those aged 16 to 17-years in recent months sowing an increase from 36.9% in August to 80.3% in October.

Seropositivity also varies by geographical region with the higher seropositivity in London and Northern regions compared to the South West throughout the surveillance period (see Table 1).

Our findings show large recent increases in seropositivity in children from September to October 2021 after a plateau which had persisted since the beginning of a phased exit out of national lockdown. Whilst increases of estimates in all age groups based on the Roche N assay indicate an increase in transmission following the start of the school academic year and is consistent with other surveillance data, the more pronounced increases seen in S-based estimates during this time period in older children reflect the deployment of a vaccine programme for 16–17 year olds. Over 80% of this age group had detectable antibodies through infection and /or vaccination by October. The initial moderately higher estimates through S-based assays during the summer months is likely to reflect early waning of antibodies in the Roche N-assay. In comparison, in those aged 12 to 15 years for whom a vaccine has been made available at the end of the reported period there was a significant increase in N-based estimates (26.6–46.9%) in October.

Seroprevalence studies are required to understand transmission dynamics and inform on the amount of asymptomatic infection; in children, almost half of all COVID−19 infection have been shown to be asymptomatic.

This study has limitations, residual samples are not collected at random but obtained from individuals undergoing diagnostic and screening tests. Individuals having to provide regular blood samples may be more vulnerable, using more precautions and thus are unlikely to be representative of the general population. However, these provide valuable information on trends over time and enable comparison with other surveillance data which show trends consistent with our findings; school based studies report large increases in the beginning of the year with a third of students seropositive by Ladhani which then stabilized over summer.

These findings highlight the importance of ongoing surveillance of paediatric seroprevalence to assess the extent of transmission in the paediatric population during the third wave and inform plans for future interventions, including the offer of a second dose to adolescents and expanding the paediatric programme with potential future availability of vaccines approved for use in children from 5 years of age. Acknowledgement: We would like to thank all hospital trusts that made this surveillance possible by providing samples throughout the pandemic.