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Self-collected finger-prick blood for gene expression profiling: Unveiling early immune responses in mild COVID-19

Year: 2025

Type: article

Abstract: Background Whole blood gene expression analysis is essential for understanding molecular host responses and identifying markers of disease severity. Self-collected finger-prick capillary blood provides a promising alternative to venous sampling, yet its application to transcriptomics is still underexplored. Methods COVERAGE-Immuno sub-study is an ancillary study of the COVERAGE France platform trial ( NCT04356495 ), a randomized controlled trial of COVID-19 early treatment in at risk patients with mild COVID-19 monitored at home. Participants recruited additional sampling for in-depth, repeated evaluation of the immunological markers and gene expression data. We compared gene expression data obtained simultaneously from venous blood (Tempus tube) and ultralow-volume fingerstick samples. Findings Our analysis revealed excellent concordance between the two sampling methods at the gene level (ICC=0·74) and a nearly perfect agreement at the geneset level. Gene expression profiles correlated well with deconvoluted cell frequencies of B and CD8+ T cells and serum biomarker IL-1b and IP-10 dynamics, offering valuable insights into SARS-CoV-2 pathophysiology. Hence, the dynamics of the immune response could be analyzed at a daily resolution, confirming early signals of neutrophil activation, interferon signaling, erythroid cell involvement, and inflammation pathways during the early stages of mild COVID-19. Interpretation These findings validate the feasibility and reliability of fingerstick sampling for at-home use, providing a unique tool for advanced clinical research and precision medicine. Funding EIT Health (Grant number: 20874 COVERAGE-Immuno) Research in context Evidence before this study Gene expression analysis of whole blood is widely used to investigate host immune responses and identify biomarkers of disease severity. While venous blood is the standard for transcriptomic studies, capillary blood sampling via self-collected finger-prick offers a less invasive and more accessible alternative, particularly for remote monitoring. However, its application to transcriptomics remains underexplored. Prior studies have demonstrated the feasibility of capillary blood for certain molecular analyses, but its reliability compared to venous sampling for gene expression profiling is not well established. Added value of this study This study provides the first comprehensive comparison of transcriptomic profiles from venous and capillary blood in a clinical trial setting. We show that gene expression measurements from self-collected fingerstick samples exhibit strong concordance with venous samples (ICC = 0·74) and near-perfect agreement at the gene set level. These findings demonstrate that capillary sampling can capture dynamic immune responses, including neutrophil activation, interferon signaling, and inflammation pathways, with correlations to key immune biomarkers (IL-1b, IP-10). Implications of all the available evidence Fingerstick-based gene expression analysis is a reliable and scalable alternative to venous blood sampling, offering a practical solution for at-home immune monitoring. These findings support its integration into clinical research and precision medicine approaches, enabling frequent, minimally invasive monitoring of immune responses in infectious diseases and beyond.

Source: iScience

DOI: 10.1016/j.isci.2025.114593