Comparing definitions of SARS-CoV-2 infection in a prospective household transmission study

Identifying SARS-CoV-2 infections in field studies, especially if they are asymptomatic or reinfections, is challenging. This study aims to compare definitions of an infection and establish an approach to detect reinfections serologically, relying on titre increase.

In a household transmission study in autumn/winter 2022, we collected information on symptoms and two serological samples in a timespan of six to eight weeks from 389 participants of the German digital cohort DigiHero. Blood samples were drawn using dried blood spot cards and analysed in regard to the SARS-CoV-2 S and N antibody. We calculated secondary attack rates (SARs) using three definitions of infection from previous literature, based on reported symptoms or seroconversion, and two approaches accounting for reinfection in serological testing.

SARs differed substantially between definitions. High initial seroprevalence in the study population led to underestimation of the SAR by over 20 % when using seroconversion compared to approaches accounting for reinfections. Symptom-based definitions resulted in misclassification likely due to infections with other pathogens and by disregarding asymptomatic cases.

This methodological study shows that relying on seroconversion is not adequate in high sero-prevalence settings and symptom-based approaches disregard asymptomatic cases. Approaches accounting for substantial titre increases between two antibody measurements reliably identified infections regardless of seroconversion and symptoms in a longitudinal serological assessment. This method could be useful for other pathogens, where asymptomatic disease and reinfections are common.