Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19

<jats:title>Abstract</jats:title><jats:p>The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8<jats:sup>+</jats:sup> T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8<jats:sup>+</jats:sup> T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c<jats:sup>+</jats:sup> conventional dendritic cells also followed this pattern, whereas CD141<jats:sup>+</jats:sup> conventional and CD123<jats:sup>hi</jats:sup> plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.</jats:p><jats:sec><jats:title>Single-sentence summary</jats:title><jats:p>Depletion from the blood and differential activation patterns of inflammatory monocytes and CD1c<jats:sup>+</jats:sup> conventional dendritic cells associate with development of ARDS in COVID-19 patients.</jats:p></jats:sec>