A public health antibody screening indicates a 6-fold higher SARS-CoV-2 exposure rate than reported cases in children

BACKGROUND: Antibody responses to virus reflect exposure and potential protection. METHODS: We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immuno-precipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (Clinicaltrials.gov NCT04039945), in 1,916 dried blood spots from neonates in a Bavarian screening study (Clinicaltrials.gov NCT03316261), and in 75 SARS-CoV-2 positive individuals. Virus positive incidence was obtained from Bavarian health authority data. FINDINGS: Dual-antibody positivity was detected in none of 3887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2 positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June and 0.91% in July. Antibody prevalence from April 2020 was six-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (P<0.0001), and was not associated with age or sex. Transmission in children with virus-positive family members was 35%; 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. CONCLUSION: We demonstrate the value of population-based screening programs for pandemic monitoring.