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)

The authors have declared no competing interest.

NCT04356495

The COVERAGE-Immuno study was funded by EIT Health (Grant number: 20874 COVERAGE-Immuno).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial protocol was approved by a French Ethics Committee: Comité de Protection des Personnes Île-de-France 1 (CPPIDF1-2020-ND45). Written informed consent was obtained from all participants. The trial protocol was registered in the European database EudraCT (2020-001435-27) and on clinicaltrials.gov (NCT04356495).

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Data supporting this study can be accessed on BioStudies database - ebi.ac.uk (E-MTAB-15066).