Profound phenotype alteration and delayed regeneration of circulating antigen presenting cells in COVID-19

Abstract Disease manifestations in COVID-19 range from mild symptoms to severe/critical illness with lung inflammation, hypercoagulation and cardiovascular complications, which may be caused by a dysregulated innate immune response. Antigen presenting cells may contribute to the inflammatory response and shape the adaptive immune response in COVID-19 patients. We therefore investigated the frequency and phenotype of circulating dendritic cells (DCs) and monocytes in hospitalized COVID-19 patients with mild/moderate or severe disease at different time points (n=65). We found an overall reduction of DCs and a shift towards the CD14+ DC3 population within the DCs in patients vs. controls. In patients with more severe disease, we observed upregulation of CXCR3, CCR2, CD40 and PD-L1, but reduced expression of CD86 and HLADR in monocytes and conventional DCs (cDCs) within the first 3 weeks after diagnosis (n=26). Increased proliferation and expansion of precursor cells in the blood indicated an enhanced turnover that was observed even in convalescent patients. Proliferating cDC2 and DC3 showed a phenotype similar to that found in healthy controls suggesting that the phenotype alterations are induced in differentiated DCs by external factors. The observed changes were accompanied by increased inflammatory cytokine levels in the plasma and lymphopenia. Thus, in more severe COVID-19 circulating cDCs and monocytes exhibited a profoundly altered expression of costimulatory molecules and were poised to exit the blood in response to inflammatory chemokines. Increased proliferation even after recovery indicated delayed regeneration of the mononuclear phagocyte system.