Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

Abstract

The COVID-19-, SARS-and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARSand MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development of COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment. 1. Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)mediated COVID-19 has emerged during the late 2019 and caused a serious public health threat, forcing the WHO to announce the SARS-CoV-2 outbreak as a pandemic [1]. SARS-CoV-2, as a member of the coronavirus family, is an enveloped virus containing a positive-sense single-stranded RNA molecule

C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis

“…During SARS-CoV-2 infections, immune cell subsets change, and among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased [44]. Interestingly, one of the characteristics of the formation of SARS-CoV-2 anti-virus antibodies in a trial to limit viral replication is that these protective antibodies will cause friendly damage by the binding of the virus-Ab complex to FcR on monocytes/macrophages induces pro-inflammatory responses that end up with the accumulation of pro-inflammatory M1 macrophages in the lungs escalating lung injury [45].…”

Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GM-CSF Induction

“…First, GM-CSF was upregulated before TNF, IL-6, and MCP-1 in animal model of SARS-CoV infection 32 , and its excessive production adversely contributed to the SARS-CoV-induced lung injury 32 . Second, consistent with the critical contribution of myeloid cells to cytokine storm 28 , the percentage of GM-CSF-expressing leukocytes was significantly increased in a subset of patients with severe COVID-19 33,34 . Thus, the excessive production of GM-CSF may adversely propagate a dysregulated cytokine storm in a subset of COVID-19 patients (Fig.…”

“…Furthermore, we have found two RBM-cross-reactive monoclonal antibodies that competitively and MCP-1). It has also been suggested as a "driver" of the disease progression particularly in a subset (~ 20%) of COVID-19 patients with more severe pneumonia that often escalates to respiratory failure and death [26][27][28][29] . Furthermore, GM-CSF might also be a key mediator of the cytokine storm in COVID-19 and other inflammatory diseases 30,31 .…”

C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis 

“…During SARS-CoV-2 infections, immune cell subsets change, and among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased [45]. Interestingly, one of the characteristics of the formation of SARS-CoV-2 anti-virus antibodies in a trial to limit viral replication is that these protective antibodies will cause friendly damage by the binding of the virus-Ab complex to FcR on monocytes/macrophages induces pro-in ammatory responses that end up with the accumulation of pro-in ammatory M1 macrophages in the lungs escalating lung injury [46].…”