Journal of Clinical Medicine (Apr 2024)

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

  • Domenico Galati,
  • Domenico Mallardo,
  • Carmine Nicastro,
  • Serena Zanotta,
  • Ludovica Capitelli,
  • Carmen Lombardi,
  • Bianca Baino,
  • Ernesta Cavalcanti,
  • Silvia Sale,
  • Francesco Labonia,
  • Rita Boenzi,
  • Luigi Atripaldi,
  • Paolo Antonio Ascierto,
  • Marialuisa Bocchino

DOI
https://doi.org/10.3390/jcm13092481
Journal volume & issue
Vol. 13, no. 9
p. 2481

Abstract

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Background: 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. Methods: 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. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p + monocytes above the median value of 114.68/μL had significantly higher in-hospital mortality (HR 4.96; 95% CI: 1.42–17.27; p = 0.02). Interleukin (IL)-6 concentrations were significantly increased in COVID-19 patients (p + cDC2 (r = −0.29, p = 0.034) and CD303+ pDC (r = −0.29, p = 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. Conclusions: 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.

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