The Dysregulation of the Monocyte-Dendritic Cell Interplay Is Associated with In-Hospital Mortality in COVID-19 Pneumonia.

The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F; mean age ± SD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. We measured frequencies and absolute numbers of peripheral blood CD169 monocytes, conventional CD1c and CD141 (namely cDC2 and cDC1), and plasmacytoid CD303 DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory-related human genes and 20 SARS-CoV-2 genes was also performed. Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls ( 0.04 and 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients ( < 0.0001). COVID-19 cases with absolute counts of CD169 monocytes above the median value of 114.68/μL had significantly higher in-hospital mortality (HR 4.96; 95% CI: 1.42-17.27; = 0.02). Interleukin (IL)-6 concentrations were significantly increased in COVID-19 patients ( < 0.0001 vs. controls), and negatively correlated with the absolute counts of circulating CD1c cDC2 (r = -0.29, = 0.034) and CD303 pDC (r = -0.29, = 0.036) subsets. Viral genes were upregulated in patients with worse outcomes along with inflammatory mediators such as interleukin (IL)-1 beta, tumor necrosis-α (TNF-α) and the anticoagulant protein (PROS1). Conversely, surviving patients had upregulated genes related to inflammatory and anti-viral-related pathways along with the T cell membrane molecule CD4. Our results suggest that the dysregulated interplay between the different components of the MPS along with the imbalance between viral gene expression and host anti-viral immunity negatively impacts COVID-19 outcomes. Although the clinical scenario of COVID-19 has changed over time, a deepening of its pathogenesis remains a priority in clinical and experimental research.