Abstract

The COVID-19 pandemic has caused more than three million deaths globally. The severity of the disease is characterized, in part, by a dysregulated immune response. CD16+ monocytes are innate immune cells involved in inflammatory responses to viral infections, and tissue repair, among other functions. We characterized the transcriptional changes in CD16+ monocytes from PBMC of people with COVID-19, and from healthy individuals using publicly available single cell RNA sequencing data. CD16+ monocytes from people with COVID-19 compared to those from healthy individuals expressed transcriptional changes indicative of increased cell activation, and induction of a migratory phenotype. We also analyzed COVID-19 cases based on severity of the disease and found that mild cases were characterized by upregulation of interferon response and MHC class II related genes, whereas the severe cases had dysregulated expression of mitochondrial and antigen presentation genes, and upregulated inflammatory, cell movement, and apoptotic gene signatures. These results suggest that CD16+ monocytes in people with COVID-19 contribute to a dysregulated host response characterized by decreased antigen presentation, and an elevated inflammatory response with increased monocytic infiltration into tissues. Our results show that there are transcriptomic changes in CD16+ monocytes that may impact the functions of these cells, contributing to the pathogenesis and severity of COVID-19.

Highlights

  • Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused more than three million deaths worldwide since December 2019 [1]

  • Unifold Manifold Approximation and Projection (UMAP) visualization of cells according to disease severity demonstrated that the severe COVID-19 group had a lower number of CD16+ monocytes compared to the group with mild COVID-19, and as compared to healthy controls (Figure 1C)

  • One study showed increased classical CD14+HLADRhi monocytes with high IFI6 and ISG15 expression in mild COVID-19 cases when compared to healthy controls [26], similar to our findings

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Summary

Introduction

Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused more than three million deaths worldwide since December 2019 [1]. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), predominantly impacts the respiratory system, and the cardiovascular, hepatic, renal, and neurologic systems. 15% of people with COVID-19 develop severe respiratory illness characterized by hypoxemia and hypoxia, resulting, in part, from Acute Respiratory Distress Syndrome (ARDS) and ventilation-perfusion mismatch [3]. This is typically accompanied by multiorgan system failure. Severe disease leads to death in approximately 1-5% of affected people [3, 4]

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