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The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to Apr