Cell type-specific immune dysregulation in severely ill COVID-19 patients: Cell Reports

https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31579-5

Cell type-specific immune dysregulation in severely ill COVID-19 patients

Highlights

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  Defective immune responses distinguish severe COVID-19 from moderate disease
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  Monocyte antigen presentation pathway gene expression is lower in severe COVID-19
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  Lymphocyte cytotoxicity pathways are reduced, and B cell activation is blunted
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  Interferon signaling is elevated in lymphocytes but diminished in monocytes

Summary

Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. We use single-cell RNA sequencing (scRNA-seq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) 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 responsiveness in monocytes from ARDS patients, which contrasts with higher responsiveness to interferon signaling in lymphocytes. Furthermore, genes involved in cytotoxic activity are suppressed in both NK and CD8 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 the innate and adaptive immune responses may be contributing to a more severe disease course.

Graphical Abstract

Article Info

Publication History

Accepted: December 10, 2020

Received in revised form: September 3, 2020

Received: July 21, 2020

Publication stage

In Press Accepted Manuscript

Footnotes

The authors have declared that no conflict of interest exists.

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