Monocytes and macrophages in COVID-19: Friends and foes

Abstract

The COVID-19 is a novel infectious disease caused by SARS-CoV-2 and is known as a pandemic emergency that has led to a high rate of mortality throughout the world. Evidence has indicated that hyperinflammatory responses triggered by SARS-CoV-2 are the main cause of pathogenicity in the severe cases of patients who have died during the current viral disease. Monocytes and macrophages as the most important cells of the innate arm of the immune system play a substantial part in the body's defense against viral infections. They mainly respond to the microbial antigens by producing inflammatory mediators to remove pathogens and repair tissue injury. Nevertheless, aberrant alterations in their function such as cytokine storm can be so harmful to the host in the acute respiratory distress syndrome cases caused by SARS-CoV-2. Moreover, inflammatory responses stimulated by SARS-CoV-2 have affected the other vital organs of the body including the heart. As cardiovascular complications in COVID-19 patients have been reported in several studies. During the infection, monocytes and macrophages may be involved in the hypersensitive and exacerbated reactions that contribute to the tissue damage, especially lung injury resulted in its dysfunction and respiratory disorder. In this review, we discuss both advantageous and disadvantageous about the pathological potential of monocytes and macrophages during the infection of SARS-CoV-2 to clarify their mutual effects on immune processing as a fist line defender in the current disease.

Keywords: COVID-19; Inflammation; Macrophage; Monocyte; SARS-CoV-2.

Graphical abstract

Fig. 1

The activity of macrophages to attenuate alveolar inflammation after lung injury and regulation of repair process which is necessary for hemostasis. For attenuating alveolar inflammation and repairing tissue damages, macrophages are involved directly and indirectly. Blockage of monocyte and granulocyte (PMN) recruitment, apoptotic parenchymal and neutrophils phagocytosis, alveolar edema fluid clearance, clearance of fibrin are macrophages activities in this process. In addition, the repairing process of the epithelial and endothelial barrier is induced by junctional sealing, ACE2 proliferation or differentiation, and angiogenesis [81].

Fig. 2

Cytokine storm damage mechanisms and new pharmaceutical interventions. Due to the attachment of SARS-CoV-2 to ACE2 in epithelial cells, the hyperinflammatory response is stimulated and epithelial cell-mediated reactive oxygen species (ROS) are produced that lead to cell death. Moreover, ROS can induce NF-Kβ and NLRP3 production which are important to trigger cytokine storm. Cytokine storm leads to some clinical condition such as sepsis, ARDS, MOF, and death. Some new clinical interventions like Emodin and Camostat mesilate have attachment prevention activity of SARS-CoV-2 to ACE2 and TMPRSS2. Flavonoid compounds modulate NLRP3 activity. Tocilizumab and GM-CSF blockers can block IL-6 and GM-CSF, respectively. NRF-2 activator drugs downregulate IL-6 and IL-1β in LPS stimulated macrophages [126]. SARS-CoV-2, severe acute respiratory syndrome 2, ROS, reactive oxygen species, MOF, multiple organ failure, PAMP, pathogen associated molecular pattern, DAMP, damaged associated molecular pattern, TNF, tumor necrosis factor, PRR, pattern recognition receptor, IL, interleukin, NLRP3, (NOD)like receptor protein 3 inflammasome, NFkβ, nuclear factor kappa B-light chain enhancer of activated B cells, NRF2, nuclear factor erythroid 2 p45-related factors 2 (NRF2), GM-CSF, granulocyte-macrophage colony-stimulating factor.