Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection

Experiments were designed to look at the relationship between infective dose and disease severity using 2 clones of Plasmodium chabaudi that differ in virulence. We asked whether there were dose–severity relationships, whether clone differences in virulence were maintained over a range of doses, and whether disease severity could be accounted for by parasite dynamics. Groups of mice were infected with parasite doses differing by an order of magnitude, ranging from 100 to 1×108 parasites. Infective dose affected the probability of death, but only with the more virulent clone. Dose also affected morbidity. For both clones, higher doses induced greater anaemia. Larger doses caused greater weight loss, but only for infections with the more virulent clone. Here, for a given dose, mice lost a fixed amount of weight, irrespective of their initial weight. Larger doses induced earlier mortality and morbidity than did lower dose treatments. Finally, dose affected parasite dynamics, with earlier and higher peak parasite densities in larger dose infections. All these effects were small relative to clone differences in disease severity, which were apparent across the range of doses. Dose effects were manifested through the timing and/or magnitude of peak parasite densities, broadly supporting the idea that dose affects disease severity by altering the time the host has to control parasite densities and ameliorate the effects of parasites. We discuss the possible efficacy of intervention strategies aimed at reducing human disease severity by reducing infective parasite dose.

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Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.592727 ◽

2021 ◽

Vol 12 ◽

Author(s):

Esmaeil Mortaz ◽

Payam Tabarsi ◽

Hamidreza Jamaati ◽

Neda Dalil Roofchayee ◽

Neda K. Dezfuli ◽

...

Keyword(s):

Disease Severity ◽

Healthy Subjects ◽

Severe Disease ◽

Serum Levels ◽

Clinical Feature ◽

Tnf Receptor ◽

Icu Patients ◽

Future Studies ◽

Tnf Α ◽

Soluble Tnf Receptor

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm.ObjectivesTo elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity.MethodsWe determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran.ResultsSerum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR.ConclusionsThe study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

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Disease severity predicts bone loss: A longitudinal study in inflammatory bowel disease patients

Gastroenterology ◽

10.1016/s0016-5085(01)83124-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A628-A628

Author(s):

S HENDERSON ◽

S DHALIWAL ◽

N HOFFMAN ◽

R PRINCE

Keyword(s):

Inflammatory Bowel Disease ◽

Longitudinal Study ◽

Bone Loss ◽

Disease Severity ◽

Bowel Disease ◽

Inflammatory Bowel

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Psoriasis Lessens Quality of Life Regardless of Disease Severity

Skin & Allergy News ◽

10.1016/s0037-6337(06)71449-8 ◽

2006 ◽

Vol 37 (8) ◽

pp. 13

Author(s):

KERRI WACHTER

Keyword(s):

Quality Of Life ◽

Disease Severity

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361 The intrinsic mitochondrial oxidative capacity of human failing hearts is depressed and relates to disease severity but keeps normal regulatory properties

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(03)90218-9 ◽

2003 ◽

Vol 2 (1) ◽

pp. 70

Author(s):

B METTAUER ◽

J ZOLL ◽

B NGUESSAN ◽

F RIBERA ◽

E LAMPERT ◽

...

Keyword(s):

Disease Severity ◽

Oxidative Capacity ◽

Mitochondrial Oxidative Capacity ◽

Regulatory Properties

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Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000667 ◽

2020 ◽

pp. 1-8

Author(s):

Jeniffer Danielle M. Dutra ◽

Quelson Coelho Lisboa ◽

Silvia Marinho Ferolla ◽

Carolina Martinelli M. L. Carvalho ◽

Camila Costa M. Mendes ◽

...

Keyword(s):

Vitamin D ◽

Liver Disease ◽

Fatty Liver ◽

Disease Severity ◽

Fatty Liver Disease ◽

Hypovitaminosis D ◽

Alcoholic Fatty Liver ◽

Vitamin D Levels ◽

The Mean ◽

Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

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