This study systematically analyzed key immunological parameters spanning the course of infection, obtained viral genomes directly from clinical samples, and delineated factors associated with prognosis and epidemiological features.

• Authors analyzed the clinical, molecular and immunological data from 326 confirmed cases of COVID-19 in Shanghai.
• Genomic sequences of SARS-CoV-2 assembled from 112 quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) showed a stable evolution and suggested two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes.
• Lymphocytopenia, especially reduced CD4+ and CD8+ T cell counts upon admission, was predictive of disease progression. High levels of IL-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count.
• The determinants of disease severity seemed to stem mostly from host factors such as age, lymphocytopenia, and its associated cytokine storm, whereas viral genetic variation did not significantly affect the outcomes.