Role of immune mediators in predicting hospitalization of SARS-CoV-2 positive patients.

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.

Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H-MRS.

We used (1)H-magnetic resonance spectroscopy to noninvasively determine total creatine (TCr), choline-containing compounds (Cho), and intracellular (IT) and extracellular (between-muscle fibers) triglycerides (ET) in three human skeletal muscles. Subjects' (n = 15 men) TCr concentrations in soleus [Sol; 100.2 +/- 8.3 (SE) mmol/kg dry wt] were lower (P < 0.05) than those in gastrocnemius (Gast; 125.3 +/- 9.2 mmol/kg dry wt) and tibialis anterior (TA; 123. 7 +/- 8.8 mmol/kg dry wt). The Cho levels in Sol (35.8 +/- 3.6 mmol/kg dry wt) and Gast (28.5 +/- 3.5 mmol/kg dry wt) were higher (P < 0.001 and P < 0.01, respectively) compared with TA (13.6 +/- 2. 4 mmol/kg dry wt). The IT values were found to be 44.8 +/- 4.6 and 36.5 +/- 4.2 mmol/kg dry wt in Sol and Gast, respectively. The IT values of TA (24.5 +/- 4.5 mmol/kg dry wt) were lower than those of Sol (P < 0.01) and Gast (P < 0.05). There were no differences in ET [116.0 +/- 11.2 (Sol), 119.1 +/- 18.5 (Gast), and 91.4 +/- 19.2 mmol/kg dry wt (TA)]. It is proposed that the differences in metabolite levels may be due to the differences in fiber-type composition and deposition of metabolites due to the adaptation of different muscles during locomotion.

Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men.

AIMS/HYPOTHESIS: To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. METHODS: Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. RESULTS: South Asians compared with Europeans had a higher mean per cent body fat (26.8% vs 22.5%, p = 0.05) and lower insulin sensitivity (mean +/- SEM 2.4 +/- 0.2 vs 3.4%/min +/- 0.3, p = 0.013). Mean (+/- SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 +/- 7.5 vs 53.6 +/- 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = -0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. CONCLUSION/INTERPRETATION: The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group.

Evaluation of the stability of the proton chemical shifts of some metabolites other than water during thermal cycling of normal human muscle tissue.

MR temperature measurements made by the chemical-shift-of-water technique in peripheral muscle of volunteers have produced larger-than-expected coefficients of change and shown significant hysteresis effects as the temperature was cycled, although these effects were not reproduced in the present study. Previous work has suggested that susceptibility effects could be a contributor to the behavior of the chemical shift data. Here, we use proton spectroscopy of muscle in conjunction with temperature cycling to evaluate the relative shifts of the water peak and those of creatine, choline, and lipids. These latter are considered not to have significant temperature coefficients of chemical shift. The results show that these lines remain very stable as the temperature is cycled, suggesting that susceptibility effects are not present in this study. The method offers the possibility that the lines can be used as frequency references if there are any questions about the stability of other moieties.

Noninvasive characterization of neonatal adipose tissue by 13C magnetic resonance spectroscopy.

In vivo 13C magnetic resonance spectroscopy (MRS) was applied noninvasively to analyze the fatty acid composition of adipose tissue in 21 full-term newborn infants and 6 mothers. In order to assess the effects of gestational and postnatal age on adipose tissue composition, we studied preterm infants at birth, term infants at the ages of 6 wk and at 6 mon. We also investigated the influence of maternal diet on infant adipose tissue composition by studying the breast-fed infants of women who maintained either an omnivore or a vegan diet. Significant differences were observed in adipose tissue composition of neonates compared with their mothers. Neonates had more saturated and less unsaturated fatty acids than their mothers (P < 0.01). We also observed changes in adipose tissue composition with maturity. From birth to 6 wk of age 13C MR spectra showed a significant increase in the amount of unsaturated fatty acids, particularly polyunsaturated fatty acids (P < 0.01). Similarly, differences were seen as a result of gestational age. Preterm infants had relatively fewer unsaturated fatty acids than full-term infants. A greater proportion of these unsaturated fatty acids were polyunsaturated. Our results demonstrate that 13C MRS can be utilized to assess noninvasively neonatal adipose tissue lipid composition and to monitor the effects of developmental changes due to gestational age and oral feeding.