Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients

Recent studies have demonstrated immunologic dysfunction in severely ill coronavirus disease 2019 (COVID-19) patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMCs) from healthy (n = 3) and COVID-19 patients with moderate disease (n = 5), acute respiratory distress syndrome (ARDS, n = 6), or recovering from ARDS (n = 6). Our data reveal transcriptomic profiles indicative of defective antigen presentation and interferon (IFN) responsiveness in monocytes from ARDS patients, which contrasts with higher responsiveness to IFN signaling in lymphocytes. Furthermore, genes involved in cytotoxic activity are suppressed in both natural killer (NK) and CD8 T lymphocytes, and B cell activation is deficient, which is consistent with delayed viral clearance in severely ill COVID-19 patients. Our study demonstrates that COVID-19 patients with ARDS have a state of immune imbalance in which dysregulation of both innate and adaptive immune responses may be contributing to a more severe disease course.

Automated summary

Recent studies have shown immunologic dysfunction in severely ill patients with COVID-19, particularly in those with ARDS, where defective antigen presentation and interferon responsiveness were observed in monocytes. There was also suppressed cytotoxic activity in NK cells and CD8 T lymphocytes, along with deficient B cell activation, indicating delayed viral clearance in severely ill patients. These findings suggest an immune imbalance in COVID-19 patients with ARDS, potentially contributing to a more severe disease course.