PMC:7456455 / 29162-32048 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7456455","sourcedb":"PMC","sourceid":"7456455","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7456455","text":"5 PERSPECTIVE\nWhat distinguishes SARS-CoV2 from other viruses, including other coronaviruses, although the hyperinflammatory storm is clearly a feature of its forerunners [6]. A strong candidate must be the expression level of ACE2 as a viral entry receptor. The host also determines the outcome of exposure to the virus. In his prescient views of the role of the external and internal host environment, Rene Dubos differed from the standard germ theory of infectious disease, as necessary, but not sufficient [77]. The pre- and post- clinical features of the present pandemic illustrate this concept superbly. Although host susceptibility and severity of infection are clearly multifactorial, there is a thread from the role of its receptor in angiotensin regulation, vascular tone and permeability, through hypertension and cardiovascular function. The connection with the metabolic syndrome suggests an unknown link to lipid metabolism, including interactions of adipocytes and macrophages [35].\nSeparate streams of the mononuclear phagocyte lineage co-exist to generate monocytic, granulocytic and dendritic cell-like monocytes [78], and the impact of COVID-19 infection on monocyte activation needs to be determined to identify targets for diagnosis and intervention. The different monocytic lineage receptors for CSF1, 2 and 3 provide direct markers of disturbed haematopoiesis and skewed cell differentiation [79]; and can be combined with downstream effectors such as CD14 [80] and FcR to determine their full activation potential. Anti-growth factor/cytokine receptor antibodies may therefore be more effective in attenuating a hyperinflammatory storm and attendant organ damage than using individual anti-cytokine reagents for GM-CSF, IL-6 and TNF, for example [22]. Recent studies with anti CSF2R blockade by mavrilimumab show promise [12,81] and anti CSF1R blockade presents an alternative or additional option. Repurposing trials of anti-inflammatory drugs have targeted a variety of macrophage pathways, with mixed results. In each case, we have to weigh potential benefits against interfering with macrophage antimicrobial and other essential functions such as antiviral-antibody dependent killing, clearance of necrotic cells and debris, and repair, as well as the risk of potentiating inflammatory responses of mononuclear phagocytes through antibody -dependent mechanisms.\nMacrophage “activation” is a complex process with limited knowledge of its regulation or variable expression in different tissues and by diverse causes [7]. Reciprocal interactions between mononuclear phagocytes and adaptive T and B lymphocyte subtypes play a decisive role in the control of macrophage activation. Further studies on monocytes from infected patients will establish how this virus manipulates innate and adaptive control mechanisms to facilitate its survival and spread 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