Macrophage responses associated with COVID-19: A pharmacological perspective

Abstract

COVID-19 has caused worldwide death and economic destruction. The pandemic is the result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has demonstrated high rates of infectivity leading to great morbidity and mortality in vulnerable populations. At present, scientists are exploring various approaches to curb this pandemic and alleviate its health consequences, while racing to develop a vaccine. A particularly insidious aspect of COVID-19 is the delayed overactivation of the body's immune system that is manifested as the cytokine storm. This unbridled production of pro-inflammatory cytokines and chemokines can directly or indirectly cause massive organ damage and failure. Systemic vascular endothelial inflammation and thrombocytopenia are potential consequences as well. In the case of COVID-19, the cytokine storm often fits the pattern of the macrophage activation syndrome with lymphocytopenia. The basis for the imbalance between the innate and adaptive immune systems is not clearly defined, but highlights the effect of SARS-CoV-2 on macrophages. Here we discuss the potential underlying basis for the impact of SARS-CoV-2 on macrophages, both direct and indirect, and potential therapeutic targets. These include granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 6 (IL-6), interferons, and CXCL10 (IP-10). Various biopharmaceuticals are being repurposed to target the cytokine storm in COVID-19 patients. In addition, we discuss the rationale for activating the macrophage alpha 7 nicotinic receptors as a therapeutic target. A better understanding of the molecular consequences of SARS-CoV-2 infection of macrophages could lead to novel and more effective treatments for COVID-19.