Prediction of Past SARS-CoV-2 Infections: A Prospective Cohort Study Among Swiss Schoolchildren.

Objective: To assess the predictive value of symptoms, sociodemographic characteristics, and SARS-CoV-2 exposure in household, school, and community setting for SARS-CoV-2 seropositivity in Swiss schoolchildren at two time points in 2020. Design: Serological testing of children in primary and secondary schools (aged 6-13 and 12-16 years, respectively) took place in June-July (T1) and October-November (T2) 2020, as part of the longitudinal, school-based study Ciao Corona in the canton of Zurich, Switzerland. Information on sociodemographic characteristics and clinical history was collected with questionnaires to parents; information on school-level SARS-CoV-2 infections was collected with questionnaires to school principals. Community-level cumulative incidence was obtained from official statistics. We used logistic regression to identify individual predictors of seropositivity and assessed the predictive performance of symptom- and exposure-based prediction models. Results: A total of 2,496 children (74 seropositive) at T1 and 2,152 children (109 seropositive) at T2 were included. Except for anosmia (odds ratio 15.4, 95% confidence interval [3.4-70.7]) and headache (2.0 [1.03-3.9]) at T2, none of the individual symptoms were significantly predictive of seropositivity at either time point. Of all the exposure variables, a reported SARS-CoV-2 case in the household was the strongest predictor for seropositivity at T1 (12.4 [5.8-26.7]) and T2 (10.8 [4.5-25.8]). At both time points, area under the receiver operating characteristic curve was greater for exposure-based (T1, 0.69; T2, 0.64) than symptom-based prediction models (T1, 0.59; T2, 0.57). Conclusions: In children, retrospective identification of past SARS-CoV-2 infections based on symptoms is imprecise. SARS-CoV-2 seropositivity is better predicted by factors of SARS-CoV-2 exposure, especially reported SARS-CoV-2 cases in the household. Predicting SARS-CoV-2 seropositivity in children in general is challenging, as few reliable predictors could be identified. For an accurate retrospective identification of SARS-CoV-2 infections in children, serological tests are likely indispensable. Trial registration number: NCT04448717.