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In this study, we aimed to investigate the relationship between blood lactate levels and lactate kinetics (lactate clearance and Δ lactate) for predicting mortality in patients with COVID-19 admitted to the emergency department. This study was performed as a retrospective study that included patients admitted to the emergency department between March 1st, 2020, and January 1st, 2022. Lactate levels were recorded at the first admission (0 h lactate) and the highest blood lactate levels in the first 24 h of follow-up (2nd highest lactate). Lactate kinetics were calculated. Clinical severity was determined according to the quick COVID Severity Index (qCSI). 300 patients were included in the study. Lactate levels at admission were similar in groups with or without mortality, but 2nd highest lactate levels were found to be significantly higher in the group with mortality (p < 0.001). Lactate clearance and ∆ lactate levels were also found to be lower in the mortality group (p < 0.001). Lactate kinetics in patients in the clinically low severity group were lower in the mortality group (p = 0.02 and p = 0.039, respectively). In the low-intermediate and high-intermediate groups, 0-h lactate and 2nd highest lactate levels were found to be higher in the mortality group, and lactate kinetics were similar in the groups with and without mortality. In the group with high clinical severity, 2nd highest lactate levels were found to be higher in the group with mortality (p = 0.010). Lactate kinetics were also found to be significantly lower in the mortality group (p < 0.001). In the high qCSI group, based on ROC analysis, the AUC for 2nd highest lactate levels predicting mortality was 0.642 (95% CI: 0.548–0.728). The optimal cut-off value for mortality was greater than >2.4 mmol/L (60.6% sensitivity, 67.4% specificity). The AUC for lactate clearance was 0.748 (95% CI: 0.659–0.824). The lactate clearance cut-off value was ≤ −177.78% (49.3% sensitivity, 100% specificity). The AUC for ∆ lactate was 0.707 (95% CI: 0.616–0.787). The optimal ∆ lactate cut-off was ≤ −2 mmol/L (45.1% sensitivity, 93.5% specificity). In COVID-19, 2nd highest blood lactate and lactate kinetics were found to be prognostic indicators of the disease. High 2nd highest lactate levels and low lactate kinetics in patients with high clinical severity were guiding physicians regarding the outcome of the disease. • Lactate has an important role in the follow-up of critically ill patients. • qCSI is an effective scoring system in the triage of critical Covid-19 patients in the emergency department. • Lactate clearance is effective in predicting mortality in critical Covid −19 patients [ABSTRACT FROM AUTHOR]

• We measured autonomic outflow and efferent metabolism before and after consumption. • We manipulated the location of nVNS stimulation in the outer ear. • The different locations were earlobe, cymba conchae, tragus, cymba conchae+tragus. • nVNS in cymba conchae decreases pre -consumption heart-rate variability. • nVNS in other locations decreases post -consumption heart-rate variability. Vagus nerve signals from the gut to brain carry information about nutrients and drive food reward. Such signals are disrupted by consuming large amounts of high-calorie foods, necessitating greater food intake to elicit a similar neural response. Non‐invasive vagus nerve stimulation (nVNS) via a branch innervating the ear is a candidate treatment for obesity in humans. There is disagreement on the optimal location of nVNS in the ear for experimental and clinical studies. There are also no studies comparing nVNS in hungry and post-prandial states. We aimed to compare ear position(s) for nVNS and explore the effects of nVNS during hungry and post-prandial states on proxies for autonomic outflow (heart-rate variability) and efferent metabolism (gastric wave frequency and resting energy expenditure). In a within-subject design, 14 participants (10 women, on average 29.4 +/- 6.7 years old) received nVNS in four different locations (cymba conchae, tragus, earlobe, or tragus AND cymba conchae) on separate days. In each session, participants were asked to consume a palatable chocolate flavored milk. With electrography on the abdomen and indirect calorimetry in a canopy, we measured electro-cardiogram, electro-gastrogram and resting energy expenditure for 15 min before and at least 35 min after consumption of the palatable drink. We also collected ratings of the palatable drink and internal and other states. Pre-drink consumption (in a hungry state) we observed no differences in the effect of location of acute nVNS on resting energy expenditure and gastric wave measures. However, nVNS in cymba conchae decreases heart-rate variability (relative to sham) and ratings of how much participants want to consume the drink (relative to tragus AND cymba conchae and a trend relative to sham). After drink consumption and with continued nVNS, gastric wave frequency is unchanged, and resting energy expenditure increases regardless of stimulation location. Heart-rate variability decreases in all locations, except cymba conchae. We also observe a trend for an increase in gastric wave amplitude in late post-drink consumption time-points in cymba conchae. We observe no support for the combined stimulation of tragus AND cymba conchae being more effective than either of the individual locations. These results suggest that nVNS in the cymba conchae in a hungry state has a similar acute effect on vagal tone as food consumption: to decrease heart rate variability. This effect then negates the usual postprandial effects of a decrease in heart rate variability as seen in the other nVNS locations. These preliminary observations suggest that nVNS in cymba conchae may act primarily on vagal afferent autonomic (and only modestly on metabolic output) in a similar way as food consumption does. [ABSTRACT FROM AUTHOR]