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Investigations of the biological variations that contribute to this risk have been hampered by heterogeneous severity, with immunologic features of critical disease potentially obscuring differences between risk groups. To examine immune heterogeneity related to demographic risk factors, we enrolled 38 patients hospitalized with clinically homogeneous COVID-19 pneumonia \u2014 defined as oxygen saturation less than 94% on room air without respiratory failure, septic shock, or multiple organ dysfunction \u2014 and performed single-cell RNA-Seq of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte\/dendritic cell (Mo\/DC) compartments, revealing altered immune cell type\u2013specific responses in higher risk COVID-19 patient subgroups. 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