SARS-CoV-2 Seroprevalence Among School-Age Children in Milan: How Has It Changed With the Fourth Pandemic Wave?

To the Editors:

Starting from December 2021, Italy was hit by a new pandemic wave of SARS-CoV-2 infection, mostly sustained by the omicron variant. To date, in Italy, around 1,168,868 equals to the 9.4 % of the total SARS-CoV-2 reported cases were found among children 0–9 years of age,[1] but, due to the fact that the infection is often asymptomatic in pediatric age, the real impact of this infection among children is difficult to estimate.

We aimed to estimate the SARS-CoV-2 antibody seroprevalence among children in February 2022 and to compare the results to those previously reported by our group in September 2020 and February 2021.

A cross–sectional SARS-CoV-2 serologic testing program using dried blood spots was implemented across 11 pre-schools and primary schools in the province of Milan. Participants 2–11 years old were investigated from the 16th of February to the 28th of February 2022. Filter papers were tested by automated GSP/DELFIA anti-SARS-CoV2 kit (PerkinElmer) targeting IgG antibodies to SARS-CoV-2 Spike protein.[2] Results were classified according to ratio values of sample absorbance over calibrator (ODs/Cal), as recommended by the manufacturer, into 3 categories: negative (<0.9), borderline (≥0.9 and <1.19) and positive (≥1.19).[3]

A total of 687 pupils participated in the study; 22 of them (2.9%) were excluded from the analysis because the blood sample collected was insufficient. Of the remaining 665 pupils, the majority (80%) were enrolled in primary schools and half (51%) of them were males. Five hundred eighteen (77%) pupils were not vaccinated for SARS-CoV-2, 42 (6%) were vaccinated with 1 dose and 105 (16%) had received a full course of vaccination. Overall, 183 of 665 (27%) participants reported a known previous infection, whereas among the 232 nonvaccinated pupils with positive serology, 93 (40%) were not aware of having had SARS-CoV-2 infection. Among 518 nonvaccinated participants, 233 were positive corresponding to a seroprevalence of 45% (95% CI: 0.40–0.49%). Complete characteristics of the study population are shown in Table 1.

TABLE 1.

Characteristics of Study Population

	Total N = 665	Pre-schools N = 128	Primary schools N = 537
Male	343 (51%)	68 (53%)	275 (51%)
Not vaccinated	518 (77%)	128 (100%)	390 (73%)
Vaccinated 1 dose	42 (6%)	0 (0%)	42 (8%)
Vaccinated 2 doses	105 (16%)	0 (0%)	105 (19%)
Previous infection	183 (27%)	26 (20%)	157 (29%)
Reported infection during the IV pandemic wave	106 (16%)	13 (10%)	93 (17%)
SARS-CoV-2 serology
Negative	251 (38%)	61 (47%)	190 (36%)
Borderline	37 (6%)	10 (8%)	27 (5%)
Positive	377 (57%)	60 (45%)	317 (59%)

Considering the average SARS-CoV-2 IgG ratio, values among fully vaccinated pupils (104) were higher than in those who reported a previous infection (136) (median 56.8, ODs/Cal vs. 6.9 ODs/Cal, respectively; T-test P = 0.0001).

The seroprevalence of SARS-CoV-2 of 45% found among nonvaccinated school children in the province of Milan, in February 2022, during the omicron predominant period, indicates a 4-fold increase when compared to data collected among schoolchildren in Milan in September 2020 (2.8%; 95% CI: 1.9–3.9%) and in February 2021 (12.5%; 95% CI: 10.6–14.6%).[4] Moreover, considering the total number of cases in the age group 0–9 as registered by the National Integrated Surveillance System, using notification of positive nasal swab, and a total population of the same age group, we estimate a SARS-CoV-2 infection cumulative incidence of 27% on February 23rd.[1] The wide gap between our findings and the incidence of documented SARS-CoV-2 infections in pediatric age (0–9 years old), though, highlights once again how the infection is often asymptomatic in the pediatric population. Moreover, we found the average SARS-CoV-2 IgG ratio among fully vaccinated children significantly higher than in those previously infected, suggesting a stronger IgG response induced by the vaccine, even though a boosting effect among vaccinated participants driven by natural infection cannot be excluded.