Do free radical NETwork and oxidative stress disparities in African Americans enhance their vulnerability to SARS-CoV-2 infection and COVID-19 severity?

Abstract

This review focuses on the hypothetical mechanisms for enhanced vulnerability of African Americans to SARS-CoV-2 infection, COVID-19 severity, and increased deaths. A disproportionately higher number of African Americans are afflicted with autoimmune and inflammatory diseases ( e.g. , diabetes, hypertension, obesity), and SARS-CoV-2 has helped expose these health disparities. Several factors including socioeconomic status, inferior health care, and work circumstances contribute to these disparities. Identifying potential inflammatory biomarkers and decreasing basal levels in high-risk individuals with comorbidities through preventive measures is critical. Immune cells, particularly neutrophils, protect us against pathogens (bacteria, fungi, and viruses) through increased generation of free radicals or oxidants and neutrophil extracellular traps (NETs) that ensnare pathogens, killing them extracellularly. However, continued generation of NETs coupled with the lack of prompt removal pose danger to host cells. NET levels are increased during pro-inflammatory diseases. COVID-19 patients exhibit elevated NET levels, depending upon disease severity. Conceivably, high-risk individuals with elevated basal NET levels would exhibit hyper-inflammation when infected with SARS-CoV-2, amplifying disease severity and deaths. Drugs inhibiting oxidant formation and vitamin supplements decreased NET formation in mice models of inflammation. Thus, it is conceivable that preventive treatments lowering NET levels and inflammation in high-risk individuals could mitigate SARS-CoV-2-induced complications and decrease mortality.

Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

“…The risk of in-hospital deaths with COVID-19 was significantly higher in patients with diabetes than those without diabetes, with hazard ratio of 2.36 ( 227 ). Because metabolic disorders are associated with NET dysfunction ( 222 , 228 , 229 ), an increase in activated neutrophils and NET formation may contribute to severe COVID-19 in patients with T2DM and obesity. Increased neutrophil-to-lymphocyte ratios have been identified as an early indicator of SARS-CoV-2 infection, predicting severe COVID-19, cytokine storm and poor clinical outcomes ( 41 , 230 ).…”

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

“…In addition to functioning as intracellular DAMPs, cholesterol crystals trigger neutrophils to release neutrophil extracellular traps (NETs) which are found in cholesterol-rich atherosclerotic plaques in apoe -/- mice and prime macrophages to release cytokines [ 55 ]. Notably, elevated serum markers of NETosis are observed in severe cases of COVID-19 [ 56 ].…”

Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans

“…More generally, reduced glutathione has been associated with various cancers, neurodegenerative diseases, Parkinson’s disease, and cystic fibrosis [ 37 ]. In fact, there are timely links to COVID-19 severity which disproportionately affects African Americans; in particular, reduced glutathione is thought to lower viral load and viral infection [ 38 – 40 ]. Needless to say, thorough investigation of these lines of evidence is beyond the scope of this work.…”