Background: Endothelial injury can be induced by coronavirus disease 2019 (COVID-19) and seems to exert a crucial pathogenic role in its most severe clinical manifestations. We aimed to investigate the association between brachial artery flow-mediated dilation (bFMD), a potential clinical and non-invasive measure of endothelial function, and in-hospital prognosis of COVID-19 patients. Methods: Brachial artery flow-mediated dilation was assessed in hospitalized COVID-19 patients within 48 h of hospital admission. The association between bFMD and either intensive care unit (ICU) admission or in-hospital death was explored using univariable and multivariable analyses. Results: Four hundred and eight patients were enrolled. Significantly lower bFMD values emerged in COVID-19 patients with either radiographic signs of pneumonia, respiratory distress, or the need for non-invasive ventilation compared with patients without these signs (p < 0.001, p = 0.001, and p < 0.001, respectively). Forty-two (10%) patients were admitted to the ICU, 76 (19%) patients died, and 118 (29%) patients met the composite endpoint of ICU admission/in-hospital death. At unadjusted Cox regression analysis showed that low bFMD (<4.4%, the median value) was associated with a higher risk for the composite endpoint of ICU admission/in-hospital death compared with high bFMD (≥4.4%, the median value) (HR 1.675, 95% CI 1.155–2.428, p = 0.007). Multi-adjusted Cox regression analyses showed that low bFMD was independently associated with a 1.519- to 1.658-fold increased risk for the composite endpoint of ICU admission/in-hospital death. Conclusions: Low bFMD predicts an unfavorable in-hospital prognosis in COVID-19 patients. The measurement of bFMD may be clinically useful in the prognostic stratification of COVID-19 patients upon hospital admission.

Background Acute viral infections, including coronavirus disease 2019 (COVID-19), are characterized by the dysregulation of iron metabolism, resulting in high serum ferritin and low iron levels. Research design and methods This study aimed to evaluate the prospective impact of iron metabolism dysregulation, as expressed by serum Ferritin-to-Iron Ratio (FIR), on the in-hospital prognosis of patients with COVID-19. Serum levels of ferritin and iron, as well as other iron metabolism markers and recognized prognostic indicators of COVID-19 severity, were measured in 362 patients consecutively hospitalized for COVID-19. The prospective relationship between FIR and the risk of the composite outcome of intensive care unit (ICU) admission/in-hospital death was analyzed. Results In the population examined (mean age 74 ± 15 years, males 55%), the rates of radiographic signs of pneumonia, respiratory distress, and the need for noninvasive ventilation were higher in patients with high FIR (≥29.2, the 75 th percentile) than in those with low FIR (<29.2, the 75 th percentile) (p < 0.05 for all comparisons). High FIR was associated with a 1.7-fold (HR 1.709, 95% CI 1.017–2.871, p = 0.043) higher risk of ICU admission/in-hospital death. Conclusions Increasing FIR values significantly and independently predicts worse in-hospital prognosis in hospitalized patients with COVID-19.

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BackgroundChronic systemic inflammation reduces the bioavailability of circulating endothelial progenitor cells (EPCs). Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme of immune tolerance catalyzing the initial step of tryptophan degradation along the so-called l-kynurenine (l-kyn) pathway, that is induced by inflammatory stimuli and exerts anti-inflammatory effects. A specific relationship between IDO1 activity and circulating EPC numbers has not yet been investigated.MethodsIn this study, circulating EPCs were examined in mice treated with low doses of lipopolysaccharide (LPS) to mimic low-grade inflammation. Moreover, the association between IDO1 activity and circulating EPCs was studied in a cohort of 277 patients with variable systemic low-grade inflammation.ResultsRepeated low doses of LPS caused a decrease in circulating EPCs and l-kyn supplementation, mimicking IDO1 activation, significantly increased EPC numbers under homeostatic conditions preventing EPC decline in low-grade endotoxemia. Accordingly, in patients with variable systemic low-grade inflammation, there was a significant interaction between IDO1 activity and high-sensitivity C-reactive protein (hs-CRP) in predicting circulating EPCs, with high hs-CRP associated with significantly lower EPCs at low IDO1 activity but not at high IDO1 activity.InterpretationOverall, these findings demonstrate that systemic low-grade inflammation reduces circulating EPCs. However, high IDO1 activity and l-kyn supplementation limit circulating EPC loss in low-grade inflammation.

A complex dysregulation of lipid metabolism occurs in COVID-19, leading to reduced total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) levels, along with a derangement of thyroid function, leading to reduced thyroid-stimulating hormone (TSH) levels. This study aimed to explore the association between TSH levels during COVID-19 and the variation (Δ) of lipid profile parameters in the period preceding (from 1 month up to 1 year) hospital admission due to COVID-19. Clinical data of 324 patients (mean age 76 ± 15 years, 54% males) hospitalized due to COVID-19 between March 2020 and March 2022 were retrospectively analyzed. The association between TSH levels at hospital admission and either Δ-TC, Δ-LDL-C, or Δ-HDL-C over the selected time frame was assessed through univariable and multivariable analyses. TSH levels were below the lower reference limit of 0.340 μUI/mL in 14% of COVID-19 patients. A significant reduction of plasma TC, LDL-C, and HDL-C was recorded between the two time points (p < 0.001 for all the comparisons). TSH was directly associated with Δ-TC (rho = 0.193, p = 0.001), Δ-LDL-C (rho = 0.201, p = 0.001), and Δ-HDL-C (rho = 0.160, p = 0.008), and inversely associated with C-reactive protein (CRP) (rho = −0.175, p = 0.004). Moreover, TSH decreased with increasing COVID-19 severity (p < 0.001). CRP and COVID-19 severity were inversely associated with Δ-TC, Δ-LDL-C, and Δ-HDL-C (p < 0.05 for all associations). A significant independent association was found between TSH and either Δ-TC (β = 0.125, p = 0.044) or Δ-LDL-C (β = 0.131, p = 0.036) after adjusting for multiple confounders including CRP and COVID-19 severity. In conclusion, lower levels of TSH may contribute to explain TC and LDL-C reduction in the acute phase of COVID-19.