COVID-19, caused by SARS-CoV-2, is an acute self-resolving disease MESHD in most of the patients, but some patients can develop a severe illness or even death MESHD. To characterize the host responses and identify potential biomarkers during disease progression MESHD, we performed a longitudinal transcriptome analysis for peripheral blood SERO mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset TRANS to recovery. We found that PBMCs at different COVID-19 disease MESHD stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection MESHD dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death MESHD, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia MESHD may exacerbate disorders in blood coagulation MESHD blood SERO coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression MESHD and predicting the risk of severity.