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

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 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).

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…Moreover, retrospective analysis demonstrates that rates of hospitalization for 2,336 Belgian subjects with T1D do not appear to be increased from February 1 to April 30, 2020, relative to hospitalization numbers for individuals without T1D ( Vangoitsenhoven et al., 2020 ). Similarly, there does not appear to be any relationship between SARS-CoV-2 positivity and development of T1D in children, including individuals at greater risk due to islet autoantibodies ( Hippich et al., 2020 ). Consistent with reduced rates of clinical infection and the generally mild course of COVID-19 in children, the available data do not support T1D as a risk factor for severe COVID-19 in children or adolescents ( Cardona-Hernandez et al., 2020 ).…”

Epidemiological analysis of 3,219 COVID-19 outbreaks in the state of Baden-Wuerttemberg, Germany.

“…9 A recent German study found a high seroprevalence in children compared to health-authority reported cases. 10 However, one cannot exclude the presence of false positives due to beta coronavirus crossreactivity in this study. 10 Second, there may be a time lag in outbreak noti cations due to information gathering processes at the level of the notifying local health o ces.…”

“…10 However, one cannot exclude the presence of false positives due to beta coronavirus crossreactivity in this study. 10 Second, there may be a time lag in outbreak noti cations due to information gathering processes at the level of the notifying local health o ces. Third, the quality of reporting in the national surveillance system varies in terms of completeness of data.…”

COVIDStrategyCalculator: A software to assess testing- and quarantine strategies for incoming travelers, contact person management and de-isolation

“…Moreover, the user can define the percent of SARS-CoV-2 cases that have actually been diagnosed. The 'percent diagnosed' has been the focus of intense research with highly conflicting predictions [77][78][79][80][81][82] . To date, there is no reliable estimate of this parameter, which is likely influenced by changes in testing strategies and variations in testing capacities over time.…”