Hyperferritinemia as a factor associated with poor prognosis in COVID-19 patients.

Worldwide, hundreds of millions of people have been infected with COVID-19 since December 2019; however, about 20% or less developed severe symptoms. The main aim of the current study was to  assess  the  relationship  between  the  severity of Covid-19 and different clinical and laboratory parameters. A total number of 466 Arabs have willingly joined this prospective cohort. Out of the total number, 297 subjects (63.7%) had negative COVID-19 tests, and thus, they were recruited as controls, while 169 subjects (36.3%) who tested positive for COVID-19 were enrolled as cases. Out of the total number of COVID-19 patients, 127 (75.15%) presented with mild symptoms, and 42 (24.85%) had severe symptoms. The age range for the participants was 20 to 82 years. Compared with controls, the severity of the disease was associated with significantly high ferritin levels (P < 0.001). The severity of the disease was also associated with a significant increase in C-reactive protein (P < 0.001), D-dimer (P < 0.001), white blood cell count (WBC) (P < 0.01), IgM (P < 0.001), and Granulocytes (P < 0.01). In addition, severe COVID-19 symptoms in the current study were associated with a significant decrease in lymphocytes (P < 0.01). There was a four-fold increase in serum ferritin levels in COVID-19 patients presented with severe symptoms upon admission. The former was associated with significantly high levels of CRP and D-dimer. Thus, hyperferritinemia, together with high CRP and D-dimer concentrations, may serve as reliable predictors for disease severity and poor prognosis in Arabs with COVID-19.

Hyperferritinemia as a factor associated with poor prognosis in COVID-19 patients.

Worldwide, hundreds of millions of people have been infected with COVID-19 since December 2019; however, about 20% or less developed severe symptoms. The main aim of the current study was to  assess  the  relationship  between  the  severity of Covid-19 and different clinical and laboratory parameters. A total number of 466 Arabs have willingly joined this prospective cohort. Out of the total number, 297 subjects (63.7%) had negative COVID-19 tests, and thus, they were recruited as controls, while 169 subjects (36.3%) who tested positive for COVID-19 were enrolled as cases. Out of the total number of COVID-19 patients, 127 (75.15%) presented with mild symptoms, and 42 (24.85%) had severe symptoms. The age range for the participants was 20 to 82 years. Compared with controls, the severity of the disease was associated with significantly high ferritin levels (P < 0.001). The severity of the disease was also associated with a significant increase in C-reactive protein (P < 0.001), D-dimer (P < 0.001), white blood cell count (WBC) (P < 0.01), IgM (P < 0.001), and Granulocytes (P < 0.01). In addition, severe COVID-19 symptoms in the current study were associated with a significant decrease in lymphocytes (P < 0.01). There was a four-fold increase in serum ferritin levels in COVID-19 patients presented with severe symptoms upon admission. The former was associated with significantly high levels of CRP and D-dimer. Thus, hyperferritinemia, together with high CRP and D-dimer concentrations, may serve as reliable predictors for disease severity and poor prognosis in Arabs with COVID-19.

OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion.

The 2',5' (OASs) are known as mediators of the antiviral response system through activation of the RNA cleavage pathway. Interestingly, we observe OAS1, OAS2 and OAS3 upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however their biological role during bacterial infection has not yet been elucidated. We observed that the expression of these genes was associated with pathogenicity and virulence of mycobacteria as infection with Mycobacterium bovis BCG failed to significantly induce OAS expression. Further, we observed that after silencing of these genes, M. tb CFU counts increased significantly 96h post-infection in comparison to the respective controls. Luminex revealed that OAS silencing significantly decreased IL-1ß, TNF-α and MCP-1 and had no effect of IL-10 secretion. We show for the first time that OAS1, 2 and 3 restrict intracellular pathogenic mycobacterial replication and enhance pro-inflammatory cytokine secretion.

The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver-enzymes, albumin, and bilirubin.

Alkaline phosphatase (ALP) is present in human preadipocytes. The aim of this study was to determine the relationship between anthropometry and serum levels of ALP isoenzymes, liver enzymes, albumin, and bilirubin. Anthropometric variables; serum total, bone, liver, and intestinal ALP levels; and alanine aminotransferase (ALT), albumin, total protein, total bilirubin, and g-glutamyltransferase serum levels were measured in 100 volunteers. The levels (given as median [interquartile range]) for total (74.0 U/L [30.0 U/L] vs 62.0 U/L [22.0 U/L]; P <.05) and liver ALP (37.3 U/L [14.6 U/L] vs 26.1 U/L [12.0 U/L]; P < .05) were higher in obese than in lean subjects. The levels of the other ALP isoenzymes and blood analytes were not significantly different between these groups. Albumin and ALT were the only blood proteins studied with serum levels that correlated significantly with waist circumference. This present study demonstrates a relationship between abdominal obesity and serum ALT levels and between body mass index and ALP levels. These findings suggest that serum ALP, particularly liver ALP, is derived from adipose and hepatic tissue.

The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue.

BACKGROUND: A previous study has demonstrated that alkaline phosphatase (AP) may play a role in the control of intracellular lipid accumulation in the rodent preadipocyte cell line, 3T3-L1. The present study investigated whether AP may have a similar function in preadipocytes isolated from human mammary gland tissue. METHODS: Preadipocyte maturation was induced in the presence or absence of the tissue non-specific AP inhibitors levamisole and histidine, and the tissue-specific AP inhibitor PheGlyGly. Cellular AP activity and adipogenesis were both assessed at 0 and 12 days post-induction of differentiation. RESULTS: After differentiation, AP activity increased 5.1 +/- 1.3-fold in the absence and 8.9 +/- 2.8-fold (P < 0.05) in the presence of levamisole. However, adipogenesis increased 1.95 +/- 0.11-fold in the absence but only 1.36 +/- 0.06-fold (P < 0.001) in the presence of levamisole. There was a 4.2 +/- 2.2-fold increase in AP activity in the absence and a 0.51 +/- 0.46-fold (P < 0.05) decrease in the presence of histidine. Adipogenesis increased 2.09 +/- 0.35-fold in the absence of histidine but only 1.22 +/- 0.30-fold (P < 0.05) in the presence of histidine. PheGlyGly had no effects. Fluorescent microscopy showed AP activity was localized to the triglyceride-containing droplets of the cell. CONCLUSION: This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes.

Ethnic differences in pre-adipocyte intracellular lipid accumulation and alkaline phosphatase activity.

Alkaline phosphatase (ALP) increases lipid accumulation in human pre-adipocytes. This study was performed to assess whether ethnic differences in the prevalence of obesity in African and European females are related to differences in pre-adipocyte lipid accretion and ALP activity. Pre-adipocytes were isolated from 13 black and 14 white females. Adipogenesis was quantified using the lipid dye, Oil red O, whilst ALP activity was assayed in cell extracts on day zero and 12days after initiating adipogenesis. Lipid levels (OD units/mg protein) were lower in pre-adipocytes from white than black females on day 0 (0.36±0.05 versus 0.44±0.03, respectively; p<0.0005) and day 12 (1.18±0.14 versus 1.80±0.22, respectively; p<0.0005), as was ALP activity (mU/mg protein) on day zero (36.5±5.8 versus 136.4±10.9, respectively; p<0.0005) and day 12 (127±16 versus 278±27, respectively; p<0.0005). Treatment of pre-adipocytes with histidine, an ALP inhibitor, blocked lipid accumulation. Thus, lipid uptake is higher in pre-adipocytes isolated from black compared to white females which parallels the obesity prevalence rates in these population groups. The reason for higher fat accumulation in pre-adipocytes isolated from black females may be related to higher ALP activity.

The relationship between alkaline phosphatase activity and intracellular lipid accumulation in murine 3T3-L1 cells and human preadipocytes.

Alkaline phosphatase (ALP) is expressed in 3T3-L1 preadipocytes, and its activity increases during adipogenesis. The purpose of this study was to determine whether ALP activity could be used as a measure of intracellular lipid accumulation in human preadipocytes and 3T3-L1 cells and which of the factors that induce adipogenesis are responsible for stimulating ALP activity. Adipogenesis was initiated in 3T3-L1 cells by incubation with differentiation medium containing insulin, dexamethasone, and 3-isobutyl-1-methylxanthine. The effect of leaving out each of the differentiation medium components was studied. Adipogenesis was also assessed in human preadipocytes and 3T3-L1 cells in the presence of the ALP inhibitor histidine. ALP activity was measured using an automated colorimetric assay and intracellular lipid accumulation was measured using the lipid-specific dye oil red O. Removal of insulin or dexamethasone from the differentiation medium had little effect on either ALP activity or lipid accumulation in 3T3-L1 cells, while removal of IBMX blocked both. Histidine inhibited ALP activity and adipogenesis in human preadipocytes and 3T3-L1 cells. Pearson univariate correlation analysis demonstrated strong correlations between ALP activity and lipid accumulation in human preadipocytes (r=0.78, n=69) and in 3T3-L1 cells (r=0.92, n=27). These data suggest that ALP and fat storage are tightly linked during preadipocyte maturation and that the measurement of ALP activity may be a novel technique for the quantification of intracellular lipid accumulation that is more sensitive and rapid than currently used methods.