INVESTIGATING THE PERIPHERAL IMMUNE LANDSCAPE OF NEUROCOVID: A SINGLE-CELL TRANSCRIPTOMICS AND PLASMA PROTEOMICS APPROACH TOWARD CLINICAL STRATIFICATION

During the COVID-19 pandemic, an increasing number of individuals started reporting a wide range of symptoms persisting months after even mild SARS-CoV2 infection, a complex multi-systemic condition, including fatigue, but also neurological, cognitive, and psychological sequelae, then clinically defined as post-COVID19 syndrome (PCS). Dysregulation of peripheral immunity may be one of the possible causes for the observed symptoms, possibly linked to sustained neuroinflammation. While some studies have reported on plasma biomarkers, considering the disease complexity and inter-individual variability, multi-site cohorts are required to efficiently determine blood biomarkers for the disease and to further refine patient stratification. As part of the European NeuroCOV consortium, this study aims to investigate potential peripheral dysregulations at the transcriptional and proteomic levels in conjunction with deep neurological and neuropsychiatric phenotyping of post-COVID-19 patients to identify the molecular immune hallmarks of the disease. For this purpose, PBMCs and plasma samples from two independent cohorts (n=284) in Italy and Germany, including recovered controls and NeuroCOVID patients, have been analyzed at the single-cell level using a multi-omics approach that includes transcriptome and surfaceome analysis. 1.5 million high-quality cell profiles highlighted signs of dysregulations affecting T cells, NK cells and the monocyte compartment. Furthermore, investigating plasma proteomics using a high-sensitivity tool with high-accuracy screening through testing n=250, even low-abundant targets, enabled us to determine dysregulated proteins that may serve as potential biomarkers of the disease. The combination of these approaches will allow for the identification of refined disease signatures across modalities for a more comprehensive understanding of the disease.