Arginase 1 (Arg1) as an Up-Regulated Gene in COVID-19 Patients: A Promising Marker in COVID-19 Immunopathy

Abstract

Background: The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic. It is well-established that SARS-CoV-2 infection can lead to dysregulated immune responses. Arginase-1 (Arg1), which has a pivotal role in immune cells, can be expressed in most of the myeloid cells, e.g., neutrophils and macrophages. Arg1 has been associated with the suppression of antiviral immune responses. Methods: Whole blood was taken from 21 COVID-19 patients and 21 healthy individuals, and after RNA extraction and complementary DNA (cDNA) synthesis, gene expression of Arg1 was measured by real-time PCR. Results: The qPCR results showed that the expression of Arg1 was significantly increased in COVID-19 patients compared to healthy individuals (p < 0.01). The relative expression analysis demonstrated there were approximately 2.3 times increased Arg1 expression in the whole blood of COVID-19 patients. Furthermore, the receiver operating characteristic (ROC) analysis showed a considerable diagnostic value for Arg1 expression in COVID-19 (p = 0.0002 and AUC = 0.8401). Conclusion: Arg1 might be a promising marker in the pathogenesis of the disease, and it could be a valuable diagnostic tool.

Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

“…4e) and CD24 (both mRNA and protein; Extended Data Fig. 6i), suggesting that additional immunomodulatory function [45][46][47][48][49] expanded with dexamethasone. Both ARG1 and ANXA1 express glucocorticoid response elements, emphasizing the possibility of their direct regulation by dexamethasone treatment 50,51 .…”

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells

“…Rees et al (12) have reported alterations in amino acid levels, including arginine and ornithine, in COVID-19 patients. Another recent paper has described increased RNA expression of Arg1 in the peripheral blood mononuclear cells of COVID-19 patients, although they did not identify the cell of origin of this Arg1 (13). Arginine depletion inhibits T cell receptor signaling resulting in T cell dysfunction (14,15).…”

Genome‐wide screening of SARS‐CoV‐2 infection‐related genes based on the blood leukocytes sequencing data set of patients with COVID‐19

“…A recently published study performed whole‐transcriptome RNA sequencing of 14 peripheral blood samples from COVID‐19 patients ( n = 10) and healthy donors ( n = 4), from which researchers screened a large number of differentially expressed mRNAs and miRNAs and constructed a lncRNA‐miRNA‐mRNA regulatory network 16 . In addition, Arg1 has recently been found to be highly expressed in the peripheral blood leukocytes of COVID‐19 patients and may be a diagnostic marker for COVID‐19 17 . These studies contribute to the understanding of gene regulatory relationships and inflammatory mechanisms in the immune cells of COVID‐19 patients and lay the foundation for the discovery of new diagnostic markers for COVID‐19.…”

“…16 In addition, Arg1 has recently been found to be highly expressed in the peripheral blood leukocytes of COVID-19 patients and may be a diagnostic marker for COVID-19. 17 These studies contribute to the understanding of gene regulatory relationships and inflammatory mechanisms in the immune cells of COVID-19 patients and lay the foundation for the discovery of new diagnostic markers for COVID- 19. However, at present, there are still few genomic studies on peripheral blood leukocytes in patients with COVID-19, and the mechanism of the abnormal inflammatory response to SARS-CoV-2 infection is still not fully understood.…”