Prevention of Severe Coronavirus Disease 2019 Outcomes by Reducing Low-Grade Inflammation in High-Risk Categories

The metabolic fingerprint of COVID-19 severity

“…While the altered cholesterol profile of severe COVID-19 can be interpreted as metabolic evidence of inflammation, it can also be construed as evidence of a genetic predisposition to severe infection, similar to what’s been shown for HDL cholestrol 54 . Relevant to the hyperinflammatory state 13 frequently identified as a “cytokine storm” in COVID-19 55 , a meta-analysis of genome-wide association studies has shown a genetic link between cytokine activity and the serum concentration of apolipoprotein B, serum cholesterol and the cholesterol and phospholipid content of IDL, LDL and VLDL 56 , all of which are shown to be lower in severe COVID-19 cases in our results. This interpretation in terms of a predisposition to severe infection finds additional support in the observed association at admission between severity and the blood biomarker score for infectious disease risk, which was constructed by Julkunen et al from biobank samples to associate to the likelihood of severe pneumonia and severe COVID-19 during eight years of follow-up 38 .…”

“…increased GlycA levels and reduced albumin levels, was associated with increased severity ( Figure 2 ). Many populations reported as high-risk for developing severe COVID-19 7 share low-grade chronic inflammation as a common feature 13 . Increased GlycA concentrations have been reported in populations with co-morbidities related to increased risk of severe COVID-19 7,9 such as advanced age 24 , diabetes 47 , obesity 48 , and CVD 21–23,33 .…”

“…ACE2 has been linked to CVD, inflammation and the metabolism through the renin-angiotensin system (RAS) 11 , and it has been shown to regulate amino acid homeostasis 12 . The populations with increased risk of developing severe COVID-19 share low-grade inflammation as a common feature 13 and the major risk factor for severe COVID-19 can be interpreted as metabolic dysregulation 14 . A clear need exists for a systemic investigation into the metabolic processes underlying the diverse immunological pathways affected by SARS-CoV-2 to better understand 1) the factors associated with risk of severe infection, 2) the systemic effects of COVID-19, and 3) the cardiometabolic complications following disease resolution.…”

“…Due to its more persistent and composite nature, being a read-out for many different inflammatory processes, GlycA can be interpreted as a summary measure of a subject’s ‘baseline’ chronic inflammatory burden 33 . In light of the common theme of low-grade inflammation in populations with higher risk for severe COVID-19 13 and reports of increased CVD risk during and following COVID-19 34 , GlycA is of particular relevance in the COVID-19 setting.…”

From ACE2 to COVID-19: A multiorgan endothelial disease

“…A feature that is shared by several medical conditions that increase COVID-19 severity is the presence of low-grade systemic inflammation ( Chiappetta et al, 2020 , Zabetakis et al, 2020 , Ciornei, 2020 ). In several studies, elevated IL-6 was associated with increased COVID-19 severity or case fatality rate ( Chen et al, 2020 , Ulhaq and Soraya, 2020 , Aziz et al, 2020 ).…”