Molecular profiling of repeated self-sampled blood reveals dynamic immune phenotypes in young adults

Abstract Population-based studies of circulating blood proteins have provided profound insights into human biology. However, short-lived changes often remained undetected. To address this, we performed a comprehensive longitudinal dried blood spot (DBS) self-sampling study in 808 young adults of the BAMSE cohort during 2020-2022. We profiled serological, autoimmune, and proteomic phenotypes in relation to SARS-CoV-2 exposures (infection, vaccination), physiological traits, genetic variation, and blood counts. Data-driven seroclustering revealed dynamic immune response to both exposures, while analysis of anti-interferon autoantibodies (AAbs) uncovered associations of pre-existing stable AAbs with prolonged COVID-19 symptoms. Genome-wide mapping determined 664 pQTLs, with cis-pQTLs associated showing increased longitudinal stability. We also identified relationships between blood cell counts and DBS proteins beyond the hematocrit effects. Paired pre- and post-exposure highlighted transient alterations for infection (e.g. LAP3) and vaccinations (e.g. TIMP3). Multi-molecular phenotyping in self-sampling can capture dynamic immune trajectories, informing precision medicine efforts with clinically valuable insights on short-term variability in health phenotypes.