SARs-CoV-2 Infection Impacts the Function and Phenotype of Plasmacytoid Dendritic Cells

Abstract Plasmacytoid dendritic cells (pDC) are innate immune cells and potent producers of interferon alpha (IFN-α). Sars-CoV-2, an RNA virus that causes Coronavirus Disease 2019 (COVID-19), has taken the lives of more than 400,000 people in the United States. Reports indicate that COVID-19 patients have reduced plasma IFN-α, suggesting a potential use of IFN-α as a disease therapeutic. However, investigations on pDC function and phenotype in COVID-19 patients are needed. We isolated peripheral blood mononuclear cells from fifty hospitalized COVID-19 patients. PBMC were stimulated with HSV-1 or Influenza A virus and IFN-α production and phenotype were assessed by flow cytometry. After stimulation, there were fewer IFN-α+ pDC from COVID-19 patients compared to controls. To reduce inflammation, COVID-19 patients may be treated with dexamethasone, a corticosteroid that has negative effects on pDC function. Although there was more impairment of pDC numbers and function in dexamethasone-treated subjects, the pDC dysregulation was also seen prior to dexamethasone treatment. Phenotypically, we identified reduced expression of pDC markers BDCA2 and CD123, and an upregulation of co-stimulatory markers on pDC from COVID-19 patients. We also observed an increased proportion of Ki67+ pDCs, which indicates increased turnover of pDCs during moderate to severe COVID-19 disease. In summary, pDC from COVID-19 patients produce significantly less IFN-α, express costimulatory ligands used to stimulate adaptive immunity, and may be undergoing rapid turnover. Overall, these changes may compromise the antiviral and adaptive immune response or represent pDC exhaustion during SARS-CoV-2 infection.