show Abstracthide AbstractIn order to characterise the temporal dynamics of host response during COVID-19, we performed a longitudinal multi-omics study using a two centre German cohort of 13 patients. Bulk RNA was extracted from peripheral blood sampled at up to 5 time points per patient. At each sample point, a patient's disease trajectory, “pseudotime”, was categorised according to clinical parameters. Both, whole transcriptome and B cell receptor sequence analysis was used to determine signatures specific to different disease trajectories. We identified coexpression modules that were associated with specific patterns across different COVID-19 disease trajectories. One module identified was related to failing interferon I response at the peak of disease severity. A second module showed biphasic upregulation of transcripts associated with erythropoiesis. Bulk BCR identified expansion of IgA+ and IgG+ cells. In sum, this study demonstrated distinct gene expression dynamics upon SARS-CoV-2 infection. Overall design: 13 patients were sampled at days 0, 2, 7, 10, 13 and/or at discharge. 1 patient with mild disease was enrolled after recovery as a recovery control. 14 Healthy donors sampled at single time point were included as controls.