Impaired function and delayed regeneration of dendritic cells in COVID-19

Winheim, Elena; Rinke, Linus; Lutz, Konstantin; Reischer, Anna; Leutbecher, Alexandra; Wolfram, Lina; Rausch, Lisa; Kranich, Jan; Wratil, Paul R.; Huber, Johanna E.; Baumjohann, Dirk; Rothenfußer, Simon; Hellmuth, Johannes C.; Scherer, Clemens; Muenchhoff, Maximilian; Bergwelt-Baildon, Michael von; Stark, Konstantin; Straub, Tobias; Brocker, Thomas; Keppler, Oliver T.; Subklewe, Marion; Krug, Anne B.

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage- HLADR+ cells lacking DC markers. Increased frequency of the recently discovered CD163+ CD14+ DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.