A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children

Med (N Y). 2021 Feb 12;2(2):149-163.e4. doi: 10.1016/j.medj.2020.10.003. Epub 2020 Oct 29.

Abstract

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 immunoprecipitation 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 the Bavarian health authority data.

Findings: Dual-antibody positivity was detected in none of the 3,887 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 6-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%.

Conclusions: We demonstrate the value of population-based screening programs for pandemic monitoring.

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

Keywords: RBD; SARS-CoV-2 antibody; nucleocapsid antigen; public health screening; receptor binding domain; seroprevalence; type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • COVID-19* / diagnosis
  • Child
  • Diabetes Mellitus, Type 1* / diagnosis
  • Humans
  • Infant, Newborn
  • Public Health
  • SARS-CoV-2

Substances

  • Antibodies, Viral

Associated data

  • ClinicalTrials.gov/NCT04039945
  • ClinicalTrials.gov/NCT03316261