Fatal COVID-19 is Associated with Reduced HLA-DR, CD123 or CD11c Expression on Circulating Dendritic Cells

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Purpose: Severe coronavirus disease 2019 (COVID-19) is linked to insufficient control of viral replication and excessive inflammation driven by an unbalanced immune response. Plasmacytoid dendritic cells (pDCs) are specialized in the rapid production of interferons in response to viral infections, and can also prime and activate T-cells. Conventional DCs (cDCs) are critical for the elimination of viral infections owing to their specialized ability to prime and activate T cells. We assessed the frequency and phenotype of pDCs and cDCs in survivors and non-survivors of COVID-19. Patients and methods: Patients with COVID-19 were enrolled, and 22 were included in this study. Peripheral whole blood was obtained during the 2 nd week of illness, stained with antibodies specific for lineage markers, human leukocyte antigen-DR isotype (HLA-DR), CD11c, and CD123, and analyzed by flow cytometry. Patients were followed-up during hospital admission and grouped into survivors (n=17) and non-survivors (n=5) of COVID-19. Results: The ratio of pDCs to pre-cDCs was significantly lower ( P =0.0005) in non-survivors compared to survivors. The frequency of pDCs was significantly higher than cDC2-like cells ( P =0.0002) and pre-cDCs ( P < 0.0001) in survivors but not in non-survivors. HLA-DR expression level on pDCs and cDC2-like cells was lower in non-survivors compared to survivors ( P =0.02 and P =0.058, respectively), and HLA-DR was inversely correlated with disease severity rating (pDCs: r = – 0.47, P =0.027; cDC2-like cells: r = – 0.45, P =0.037). CD123 expression level on pDCs was significantly lower ( P =0.038) in non-survivors compared to survivors, and CD123 was inversely correlated with disease severity rating ( r =– 0.5, P =0.016). CD11c expression level on cDC2-like cells was significantly lower ( P =0.03) in non-survivors compared to survivors, and CD11c was inversely correlated with disease severity rating ( r =– 0.47, P =0.025). Conclusion: A lower frequency of pDCs compared to other circulating DCs, and lower expression levels of HLA-DR, CD123 or CD11c on DCs is associated with fatal COVID-19. Keywords: SARS-CoV-2, COVID-19, inflammation, innate immunity, plasmacytoid dendritic cells, conventional dendritic cells

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