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Hippich, M. ; Holthaus, L. ; Assfalg, R.* ; Zapardiel-Gonzalo, J. ; Kapfelsperger, H. ; Heigermoser, M. ; Haupt, F. ; Ewald, D.A.* ; Welzhofer, T.C.* ; Marcus, B.A.* ; Heck, S. ; Koelln, A. ; Stock, J. ; Voss, F. ; Secchi, M.* ; Piemonti, L.* ; Rosa, K.* ; Protzer, U. ; Boehmer, M.* ; Achenbach, P. ; Lampasona, V.* ; Bonifacio, E. ; Ziegler, A.-G.

Public health antibody screening indicates a six-fold higher SARS-CoV-2 exposure rate than reported cases in children.

Med. 2, 149-163.e4 (2021)

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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. Funding: The work was supported by funding from the BMBF (FKZ01KX1818).

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