Multi-molecular phenotyping in a self-sampling population

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Abstract

The recent COVID-19 pandemic has posed major health challenges. To expand our molecular understanding beyond those seeking medical care, we conducted a cross-sectional survey targeting random residents from Sweden’s two largest cities.

Two thousand participants were invited during 2021 to self-sample dried blood spots (DBS) and provide health information. DBS samples were analysed for multiple anti-SARS-CoV-2 antibodies (Abs), auto-reactive antibodies (AAbs) against 23 interferons (IFNs), and for 502 circulating immune-related proteins. Data-driven methodologies characterised the DBS phenotypes in response to infections and vaccination.

We received DBS samples from 437 (22%) volunteers aged 18-69, 60% females, and 50% per city. Multi-analyte serology distinguished self-reported infections (26%) and vaccination (40%), revealing a time-dependent discrepancy between reported and measured immunity. Anti-IFN Abs were detected in 21% of the donors and more frequent for type 1 IFNs alongside a natural infection. Integrating proteomics with antibody data provided additional insights into processes of cell-mediated immunity. Proteomics-centric analysis identified 24% of the participants to deviate in their phenotypes due to infection, immunity, respiratory distress, and age-related traits.

Multi-molecular analysis of layperson samples uncovered heterogeneity and diversity of immunity and health phenotypes, complementing clinical investigations.

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