Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study

Abstract

The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients.

The Neutrophil-to-Monocyte Ratio and Lymphocyte-to-Neutrophil Ratio at Admission Predict In-Hospital Mortality in Mexican Patients with Severe SARS-CoV-2 Infection (Covid-19)

“…In humans, neutrophils are the most abundant type of peripheral WBC with prominent functions in the acute inflammatory response by migrating toward injured tissues in response to chemoattractant signals such as interleukin (IL-) 8 [ 29 ]. Neutrophils are now considered one of the most important immune cells in defending the airway epithelium against the SARS-CoV-2 infection by locally stimulating the production of IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and reactive oxygen species (ROS) [ 30 ]. Paradoxically, neutrophil hyperactivation and recruitment intensify the acute inflammatory response and worsen epithelial tissue damage thus leading to disease progression [ 30 , 31 ].…”

“…Neutrophils are now considered one of the most important immune cells in defending the airway epithelium against the SARS-CoV-2 infection by locally stimulating the production of IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and reactive oxygen species (ROS) [ 30 ]. Paradoxically, neutrophil hyperactivation and recruitment intensify the acute inflammatory response and worsen epithelial tissue damage thus leading to disease progression [ 30 , 31 ]. On the contrary, lymphocytes are very important leukocytes in charge of mediating immune tolerance to self-antigens, activation of pathogen-specific adaptive immunity, and, last but not less important, orchestration of immunomodulatory mechanisms [ 32 , 33 ].…”

In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

“…Recently, the role of neutrophils in severe COVID-19 has received immense attention. Specifically, a microarray-based study of SARS-CoV-2 infected a peripheral blood mononuclear cell (PMBC) and single cell analysis of epithelial and immune cells in COVID-19 patients revealed that the neutrophil markers were overexpressed, suggesting that the patients were under neutrophilia [9,10]. Furthermore, a meta-analysis based on gene network constructed from the published datasets derived several neutrophil-enriched genes [11].…”

The immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2: Vaccine design strategies

“…Activation and degranulation of these cells in the microenvironment of infected cells can damage the host tissue and worsen the disease outcome. The neutrophils, via the induction of pro-inflammatory cytokines, as well as ROS production, could worsen the disease manifestation [64] . It is suggested that severe host response in the infected patients with COVID-19 is due to improper activation of leukocytes such as neutrophils in peripheral blood.…”