Longitudinal change in SARS-CoV-2 seroprevalence in 3-to 16-year-old children: The Augsburg Plus study

Abstract

Background Currently, more than 30,200,000 COVID-19 cases have been diagnosed in Germany alone. However, data regarding prevalence of COVID-19 in children, both in Germany and internationally, are sparse. We sought to evaluate the number of infected children by measuring IgG antibodies. Methods Oropharyngeal swabs were collected between December 2020 and August 2021 to measure SARS-CoV-2, and capillary blood for the detection of SARS-CoV-2 antibodies (by rapid test NADAL® and filter paper test Euroimmun® ELISA); venous blood was taken for validation (Roche® ECLIA and recomLine Blot) in 365 German children aged 3–16 years from 30 schools and preschools. We used multiple serological tests because the filter paper test Euroimmun® ELISA performs better in terms of sensitivity and specificity than the rapid test NADAL®. The Roche® ECLIA test is used to detect SARS-CoV-2 spike protein, and the recomLine Blot test is used to rule out the possibility of infection by seasonal SARS-viruses and to test for specific SARS-CoV-2 proteins (NP, RBD and S1). In addition, one parent each (n = 336), and 4–5 teachers/caregivers (n = 90) per institution were tested for IgG antibodies from capillary blood samples. The total study duration was 4 months per child, including the first follow-up after 2 months and the second after 4 months. Results Of 364 children tested at baseline, 3.6% (n = 13) were positive for SARS-CoV-2 IgG antibodies using Euroimmun® ELISA. Seven children reported previously testing positive for SARS-CoV-2; each of these was confirmed by the Roche® Anti-SARS-CoV-2-ECLIA (antibody to spike protein 1) test. SARS-CoV-2 IgG antibodies persisted over a 4-month period, but levels decreased significantly (p = 0.004) within this timeframe. The median IgG values were 192.0 BAU/ml [127.2; 288.2], 123.6 BAU/ml [76.6; 187.7] and 89.9 BAU/ml [57.4; 144.2] at baseline, 2 months and 4 months after baseline, respectively. During the study period, no child tested positive for SARS-CoV-2 by oropharyngeal swab. A total of 4.3% of all parents and 3.7% of teachers/caregivers tested positive for IgG antibodies by Euroimmun® ELISA at baseline. Conclusion We noted a rather low seroprevalence in children despite an under-reporting of SARS-CoV-2 infections. Measurement of IgG antibodies derived from capillary blood appears to be a valid tool to detect asymptomatic infections in children. However, no asymptomatic active infection was detected during the study period of 4 months in the whole cohort. Further data on SARS-CoV-2 infections in children are needed, especially in the group of <5-year-olds, as there is currently no licensed vaccine for this age group in Germany. The Robert Koch Institute’s Standing Commission on Vaccination (STIKO) recommended COVID-19 vaccination for 12–17 and 5–11 year olds in August 2021 and May 2022 respectively.

Seroprevalence, seroconversion, and seroreversion of infection-induced SARS-CoV-2 antibodies among a cohort of children and adolescents in Montreal, Canada

“…5–8 Few data are available on seroreversion in children, although a few cohort studies have found that IgG antibodies waned (yet remained detectable), starting at two months up to 18 months post-infection, with higher antibody levels consistently observed among younger children. 7,9–13…”

“…Among seropositive individuals, estimates of antibody waning are variable with some suggesting that seroreversion occurs more rapidly among younger adults and those with mild or asymptomatic infections. [5][6][7][8] Few data are available on seroreversion in children, although a few cohort studies have found that IgG antibodies waned (yet remained detectable), starting at two months up to 18 months post-infection, with higher antibody levels consistently observed among younger children. 7,[9][10][11][12][13] In this prospective population-based cohort study, we used serological testing to assess the prevalence, seroconversion, and seroreversion of anti-SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada.…”

“…[5][6][7][8] Few data are available on seroreversion in children, although a few cohort studies have found that IgG antibodies waned (yet remained detectable), starting at two months up to 18 months post-infection, with higher antibody levels consistently observed among younger children. 7,[9][10][11][12][13] In this prospective population-based cohort study, we used serological testing to assess the prevalence, seroconversion, and seroreversion of anti-SARS-CoV-2 antibodies in children and adolescents in Montreal, Canada. We also identified characteristics of study participants associated with increased risk of SARS-CoV-2 seropositivity.…”

COVID-19 vaccination in children and adolescents

“…Bei der Beurteilung der Krankheitslast im Kontext eines pandemischen neuen Erregers, der bei Kindern häufig zu asymptomatischen Infektionen führt – wie bei der SARS-CoV‑2-Infektion – sind im Rahmen der Definition von Zähler und Nenner unterschiedliche Aspekte zu berücksichtigen: Der zeitliche Verlauf aller, einschließlich der asymptomatischen Infektionen (Nenner) ist beurteilbar durch: repetitive Untersuchung einer Kohorte oder durch Zeitreihen (wiederholte Querschnittuntersuchungen) mit Bestimmung von serologischen Markern (Enzyme-linked Immunosorbent Assay, ELISA; [ 14 ]). Zur Bestimmung der Seroprävalenz liegen aus Deutschland mehrere Querschnittuntersuchungen vor [ 1 , 8 , 10 , 14 , 18 ]. Die größte Studie mit über 10.000 Kindern und Jugendlichen wurde durch Bundesförderung möglich [ 14 ] und wurde deshalb hier als eine Quelle der Beurteilung der Häufigkeit von SARS-CoV‑2-Infektionen verwendet.…”

“…Randomisierte Studien zur Effektivität der COVID-19-Kinderimpfstoffe erfolgten überwiegend in den ersten Jahren der Pandemie, weil nur dann ausreichend große Kohorten SARS-CoV‑2-naiver Kinder rekrutiert werden konnten. Sie berichten als Endpunkt „Erkrankung an COVID-19“, betrafen frühe VOC und zeigten eine akzeptable Effektivität zur Reduktion des Erkrankungsrisikos [ 5 , 10 , 15 ].…”