SARS-COV-2 IgG positivity in vaccinated and non-vaccinated Chilean children: a national cross-sectional study in schools.

Introduction

COVID-19 vaccination of children is gaining global support (Committee on Infectious Diseases, 2022), and data on immunogenicity and efficacy/effectiveness are increasing (Walter et al., 2022; Frenck et al., 2021; Han et al., 2021). Chile has rapidly advanced in a national vaccination campaign for children: as of February 17, 2022, 79% of children aged 3–17 years have been fully vaccinated (Ministerio de Salud Chile, 2022). Children aged 12–17 years have been vaccinated since June 22, 2021, with the mRNA Pfizer/BioNTech vaccine, followed weeks later by children aged 6–11 years, who received the inactivated Sinovac vaccine. We previously reported a national COVID-19 IgG seropositivity study in adults vaccinated with either vaccine that demonstrated the utility of large cross-sectional immunologic surveys using lateral flow tests (LFTs) (Sauré et al., 2022). In this study, we reported IgG seropositivity in vaccinated and non-vaccinated Chilean school-aged children who received the inactivated vaccine from Sinovac (CoronaVac) or the mRNA vaccine from Pfizer/BioNTech (BNT162b2) within 1–20 weeks before sample collection, or no vaccine. Data on IgG seropositivity among vaccinated children with inactivated as compared with mRNA vaccines are currently non-existent and can provide important information for decision-makers worldwide.

Methods

We performed SARS-CoV-2 IgG testing using the OnSite (CTK Biotech Inc, Poway, CA, US) LFT. This was the same LFT as the one used in adults (Sauré et al., 2022), with reported sensitivity and specificity of 96.7% and 98.1%, respectively (CTK Biotech, 2021). In conjunction with the Chilean Ministries of Education and Health, 24 schools located in the three most populated regions in Chile were invited to take part in the study. Briefly, all parent/children pairs were invited to participate through a letter sent by school authorities. Accepting parents signed informed consent, and children aged >8 years an assent. Children of every accepting parent were tested. Trained staff in each school obtained basic information from the parent/caregiver of the child participant, including type of vaccine and vaccination dates, age, gender, country of origin, general medical history, previous COVID-19 IgG or polymerase chain reaction testing, home address and usual transportation method to school. A finger-prick blood sample was obtained from children as previously described (Sauré et al., 2022). Tests were read on-site and results (positive, negative, or not conclusive) and surveillance data were instantly uploaded through a web interface to a database harbored at the Instituto Sistemas Complejos de Ingeniería, as in previous reports (Sauré et al., 2022). The study was approved by the Comité de Ética de Investigación en Seres Humanos (Universidad de Chile, Santiago, Chile).

Results

As of December 24, 2021, a total of 2302 children have been included, as described in Table 1 . Whereas most Sinovac recipients were aged 6–11 years (920), Pfizer/BioNTech recipients were almost exclusively aged 12–18 years (647). IgG positivity was significantly higher in Pfizer than in Sinovac recipients for all study variables except comorbidities (Table 1). In 670 children receiving the Pfizer/BioNTech vaccine, seropositivity was 91.7% three to four weeks after the second dose, with figures above 90% by 20 weeks after full vaccination (Fig. 1 ). In 1506 children receiving Sinovac, seropositivity was 91.8 % three to four weeks after the second dose, with a declining trend thereafter (Fig. 1).

Table 1

Covid-19 IgG positivity according to population characteristics and vaccine receiveda.

Characteristics	Total		Unvaccinated		Sinovac		Pfizer
	n/N	IgG positivity (95% CI)	n/N	IgG positivity (95% CI)	n/N	IgG positivity (95% CI)	n/N	IgG positivity (95% CI)
Age range
6–11 years	837/1033	81.0% (78.6%, 83.4%)	25/90	27.8% (18.5%, 37.0%)	792/920	86.1% (83.9%, 88.3%)	20/23	87.0% (73.2%, 100%)
12–18 years	1136/1269	89.5% (87.8%, 91.2%)	7/31	22.6% (7.9%, 37.3%)	505/591	85.4% (82.6%, 88.3%)	624/647	96.4% (95.0%, 97.9%)
Gender
Male	866/1001	86.5% (84.4%, 88.6%)	15/62	24.2% (13.5%, 34.9%)	598/678	88.2% (85.8%, 90.6%)	253/261	96.9% (94.8%, 99.0%)
Female	1107/1301	85.1% (83.2%, 87.0%)	17/59	28.8% (17.3%, 40.4%)	699/833	83.9% (81.4%, 86.4%)	391/409	95.6% (93.6%, 97.6%)
Region
Metropolitan	1301/1459	89.2% (87.6%, 90.8%)	19/72	26.4% (16.2%, 36.6%)	920/1021	90.1% (88.3%, 91.9%)	362/366	98.9% (97.8%, 100%)
Valparaíso	374/461	81.1% (77.6%, 84.7%)	12/36	33.3% (17.9%, 48.7%)	238/292	81.5% (77.1%, 86.0%)	124/133	93.2% (89.0%, 97.5%)
Biobío	298/381	78.2% (74.1%, 82.4%)	1/13	7.7% (0%, 22.2%)	139/197	70.6% (64.2%, 76.9%)	158/171	92.4% (88.4%, 96.4%)
Prev. pos. PCRb	35/45	77.8% (65.6%, 89.9%)	3/6	50.0% (10.0%, 90.0%)	20/27	74.1% (57.5%, 90.6%)	12/12	100% (100%, 100%)
Comorbidities
Obesity	50/56	89.3% (81.2%, 97.4%)	1/6	16.7% (0%, 46.5%)	38/39	97.4% (92.5%, 100%)	11/11	100% (100%, 100%)
Chronic pulmonary disease	82/94	87.2% (80.5%, 94.0%)	1/4	25.0% (0%, 67.4%)	33/40	82.5% (70.7%, 94.3%)	48/50	96.0% (90.6%, 100%)
Cardiovascular	13/14	92.9% (79.4%, 100%)	0/0	-	6/7	85.7% (59.8%, 100%)	7/7	100% (100%, 100%)
Otherc	8/9	88.9% (68.4%,100%)	0/0	-	0/0	-	8/9	88.9% (68.4%, 100%)
None identified	1820/2129	85.5% (84.0%, 87.0%)	30/111	27.0% (18.8%, 35.3%)	1220/1425	85.6% (83.8%, 87.4%)	570/593	96.1% (94.6%, 97.7%)
Total	1973/2302	85.7% (84.3%, 87.1%)	32/121	26.4% (18.6%, 34.3%)	1297/1511	85.8% (84.1%, 87.6%)	644/670	96.1% (94.7%, 97.6%)

CI, confidence interval; PCR, polymerase chain reaction.

The data exclude participants with incomplete information (n=6), inconsistent vaccination status information (n=86), region other than those listed (n=1) and those vaccinated with vaccines other than Sinovac or Pfizer (n=11)

Positive PCR previously obtained

Includes four cases of hypertension, four cases of diabetes and one case of cancer.

Fig. 1

Seropositivity one to four weeks after first dose (light blue-shaded region) or after second dose for recipients of Sinovac or Pfizer vaccines with no prior positive PCR result.

Discussion

In school-aged Chilean children, SARS-CoV-2 IgG seropositivity surpassed 90% two weeks after the administration of a second dose in the case of the inactivated vaccine (Sinovac), and up to 10 weeks after administering a second dose in the case of the mRNA vaccine (Pfizer/BioNTech). Compared with the adult population (Sauré et al., 2022), children showed a slightly weaker response to the mRNA vaccine and a slightly stronger response to the inactivated vaccine in terms of the overall proportion of seropositive individuals in the short-term period after vaccination. Nevertheless, in the case of adults, seropositivity in the inactivated vaccine recipients declines over time, suggesting that a booster dose will most likely be required for children; however, by 22–24 weeks after immunization, we reported a small sample size for the inactivated vaccine. LFTs do not differentiate IgG responses due to vaccination vs infection, which may have influenced some of the responses observed; positivity in a small number of non-vaccinated children reached 27%. Self-reporting of child characteristics reduces robustness for the comparison of comorbidities.

Chile was one of the first Western countries to begin vaccinating children (Ministerio de Salud 2021), a decision that may be relevant given the scenario of circulation of more transmissible variants. With the Omicron variant, SARS-CoV-2 infections and hospitalizations reached high levels in children, but severe clinical outcomes were less frequent than with the Delta variant in this population (Wang et al., 2022). The impact of the COVID-19 vaccines on protection against infection and especially severe disease has yet to be elucidated in children. However, immunization of children could have an impact on both direct and indirect effects of SARS-CoV-2 infection, favoring school attendance, mental health and cognitive learning, especially in vulnerable children (Fore, 2020).

Declaration of Competing Interest

The authors have no conflicts of interest relevant to this article to disclose.