Key patient demographics shape innate immune topography in non-critical hypoxic COVID-19 pneumonia
Risk of severe disease and death due to coronavirus 2019 (COVID-19) is increased in certain patient demographic groups, including those who are of advanced age, male sex, and obese body mass index. 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 – defined as oxygen saturation <94% on room air without respiratory failure, septic shock, or multiple organ dysfunction – and performed single-cell RNA-sequencing of leukocytes collected at admission. Examination of individual risk factors identified strong shifts within neutrophil and monocyte/dendritic cell compartments, revealing altered immune cell type-specific responses in higher-risk COVID-19 patient subgroups. Specifically, we found transcriptional evidence of altered neutrophil maturation in aged versus young patients and enhanced cytokine responses in monocytes/dendritic cells of male versus female patients. Such innate immune cell alterations may contribute to outcome differences linked to these risk factors. They also highlight the importance of diverse patient cohorts in studies of therapies targeting the immune response in COVID-19. Overall design: Study involved enrollment of 38 patients presenting to the hospital with COVID-19 and 3 healthy controls. See paper Methods for inclusion/exclusion criteria. Whole blood was collected within 1 day of hospitalization and buffy coats isolated for generation of scRNA-seq libraries. No replicates are included.