scholarly journals Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
◽  
Heli Julkunen ◽  
Anna Cichońska ◽  
P Eline Slagboom ◽  
Peter Würtz
Keyword(s):  
General Population ◽  
Disease Onset ◽  
Severe Pneumonia ◽  
Blood Sampling ◽  
Low Grade ◽  
Healthy Individuals ◽  
Metabolic Biomarkers ◽  
Low Grade Inflammation ◽  
Increased Susceptibility

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

scholarly journals Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population

2019 ◽  
Vol 65 (2) ◽  
pp. 321-332 ◽  
Author(s):  
Signe E J Hansen ◽  
Christian M Madsen ◽  
Anette Varbo ◽  
Børge G Nordestgaard
Keyword(s):  
Acute Pancreatitis ◽  
General Population ◽  
Low Grade ◽  
General Population Study ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Heart Study ◽  
Blood Leukocyte ◽  
Low Grade Inflammation ◽  
Multivariable Adjustment

Abstract BACKGROUND How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177–886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10−17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10−17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10−6), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10−4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

scholarly journals Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

2020 ◽  
Vol 9 (9) ◽  
pp. 3006
Author(s):  
Vadim V. Klimontov ◽  
Anton I. Korbut ◽  
Nikolai B. Orlov ◽  
Maksim V. Dashkin ◽  
Vladimir I. Konenkov
Keyword(s):  
Growth Factors ◽  
Kidney Disease ◽  
Low Grade ◽  
Hs Crp ◽  
Low Grade Inflammation ◽  
Egfr Decline ◽  
Multiplex Bead ◽  
Circulating Cytokines

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; albuminuria and eGFR <60 mL/min/1.73 m2. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

scholarly journals Serum Calprotectin and Chemerin Concentrations as Markers of Low-Grade Inflammation in Prepubertal Children with Obesity

2020 ◽  
Vol 17 (20) ◽  
pp. 7575 ◽  
Author(s):  
Grażyna Rowicka ◽  
Hanna Dyląg ◽  
Magdalena Chełchowska ◽  
Halina Weker ◽  
Jadwiga Ambroszkiewicz
Keyword(s):  
Low Grade ◽  
Serum Concentrations ◽  
C Reactive Protein ◽  
Prepubertal Children ◽  
Reactive Protein ◽  
Study Population ◽  
Normal Body Weight ◽  
Wbc Count ◽  
Low Grade Inflammation

In adults, obesity is associated with chronic low-grade inflammation, which may cause long-term adverse health consequences. We evaluated whether obesity in prepubertal children also generates this kind of inflammation and whether calprotectin and chemerin may be useful markers for early detection of such inflammation in this group of children. The study population included 83 children aged 2 to 10 years; 62 with obesity and without components of metabolic syndrome and 21 healthy controls with normal body weight. White blood cell (WBC) count, concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), calprotectin, and chemerin were determined in peripheral blood. Our study showed that in the group with obesity, serum concentrations of calprotectin and chemerin, as well as CRP were significantly higher as compared with the controls. We found a significant positive correlation between serum chemerin concentrations and BMI z-score (r = 0.33, p < 0.01) in children with obesity. Chemerin concentration was also positively correlated with CRP level (r = 0.36, p < 0.01) in the whole group of children. These findings suggest that obesity may generate chronic low-grade inflammation as early as in the prepubertal period which can be indicated by significantly higher serum concentrations of calprotectin and chemerin. Calprotectin and especially chemerin seem to be promising indicators of this type of inflammation in children with obesity, but the correlation between these markers requires further research.

scholarly journals Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71875 ◽  
Author(s):  
Helen G. L. Gao ◽  
Paul W. Fisher ◽  
Alex G. Lambi ◽  
Christine K. Wade ◽  
Ann E. Barr-Gillespie ◽  
...  
Keyword(s):  
Upper Extremity ◽  
Rat Model ◽  
Low Grade ◽  
Low Grade Inflammation

scholarly journals Elevated alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality

2018 ◽  
Author(s):  
Scott C. Ritchie ◽  
Johannes Kettunen ◽  
Marta Brozynska ◽  
Artika P. Nath ◽  
Aki S. Havulinna ◽  
...  
Keyword(s):  
Disease Risk ◽  
Severe Disease ◽  
Disease Onset ◽  
Population Based ◽  
Morbidity And Mortality ◽  
Low Grade ◽  
Elevated Expression ◽  
Long Term Follow Up ◽  
Alpha 1 Antitrypsin

AbstractIntegration of electronic health records with systems-level biomolecular data has led to the discovery that GlycA, a complex nuclear magnetic resonance (NMR) spectroscopy biomarker, predicts long-term risk of disease onset and death from myriad causes. To determine the molecular underpinnings of the disease risk of the heterogeneous GlycA signal, we used machine learning to build imputation models for GlycA’s constituent glycoproteins, then estimated glycoprotein levels in 11,861 adults across two population-based cohorts with long-term follow-up. While alpha-1-acid glycoprotein had the strongest correlation with GlycA, our analysis revealed that alpha-1 antitrypsin (AAT) was the most predictive of morbidity and mortality for the widest range of diseases, including heart failure (HR=1.60 per s.d., P=1×10−10), influenza and pneumonia (HR=1.37, P=6×10−10), and liver diseases (HR=1.81, P=1×10−6). Despite emerging evidence of AAT's role in suppressing inflammation, transcriptional analyses revealed elevated expression of diverse inflammatory immune pathways with elevated AAT levels, suggesting AAT is elevating to compensate for low-grade chronic inflammation. This study clarifies the molecular underpinnings of the GlycA biomarker and its associated disease risk, and indicates a previously unrecognised association between elevated AAT and severe disease onset and mortality.

scholarly journals Low-grade inflammation is negatively associated with physical Health-Related Quality of Life in healthy individuals: Results from The Danish Blood Donor Study (DBDS)

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0214468 ◽  
Author(s):  
Khoa Manh Dinh ◽  
Kathrine Agergård Kaspersen ◽  
Susan Mikkelsen ◽  
Ole Birger Pedersen ◽  
Mikkel Steen Petersen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Health ◽  
Blood Donor ◽  
Low Grade ◽  
Health Related Quality ◽  
Healthy Individuals ◽  
Related Quality ◽  
Health Related ◽  
Low Grade Inflammation

scholarly journals Implication of Aging Related Chronic Neuroinflammation on COVID-19 Pandemic

2020 ◽  
Vol 10 (3) ◽  
pp. 102 ◽  
Author(s):  
Paola Bossù ◽  
Elisa Toppi ◽  
Valentina Sterbini ◽  
Gianfranco Spalletta
Keyword(s):  
Severe Disease ◽  
Severe Case ◽  
Innate Immune ◽  
Low Grade ◽  
Chronic Neuroinflammation ◽  
Low Grade Inflammation ◽  
The Brain ◽  
Neuropsychiatric Conditions

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, leads to a respiratory syndrome and other manifestations. Most affected people show no or mild symptoms, but the risk of severe disease and death increases in older people. Here, we report a narrative review on selected studies targeting aging-related chronic neuroinflammation in the COVID-19 pandemic. A hyperactivation of the innate immune system with elevated levels of pro-inflammatory cytokines occurs during severe COVID-19, pointing to an important role of the innate immune dysregulation in the disease outcome. Aging is characterized by a general condition of low-grade inflammation, also connected to chronic inflammation of the brain (neuroinflammation), which is involved in frailty syndrome and contributes to several age-associated diseases, including neurodegenerative and neuropsychiatric disorders. Since neuroinflammation can be induced or worsened by the virus infection itself, as well as by stressful conditions like those linked to the recent pandemic, the role of neuroinflammatory mechanisms could be central in a vicious circle leading to an increase in the mortality risk in aged COVID-19 patients. Furthermore, triggered neuroinflammatory pathways and consequent neurodegenerative and neuropsychiatric conditions might be potential long-term complications of COVID-19. In order to provide insights to help clinicians in identifying patients who progress to a more severe case of the disease, this review underlines the potential implications of aging-related neuroinflammation in COVID-19 pandemic.

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