Arterial vessels express one or more heme oxygenase (HO) isoenzymes that catalyze the metabolism of heme to carbon monoxide (CO) and biliverdin. Carbon monoxide promotes vasorelaxation through mechanisms that, depending on the vessels, involve activation of soluble guanylate cyclase, stimulation of calcium-activated potassium channels, or diminished synthesis of constrictor mediators, such as, endothelin and 20-HETE. Inhibitors of HO elicit vasoconstriction in vivo and in isolated pressurized arterioles. Inhibitors of HO also enhance myogenic vasoconstriction, as well as the constriction induced by phenylephrine in several vessels. The blood pressure of awake rats is increased by acute treatment with HO inhibitors, a response that is accompanied by attenuation of baroreflex activity. All in all, it would appear that a product of HO activity manufactured by arterial vessels, presumably CO, promotes vasodilation and decreases the reactivity of vascular smooth muscle to myogenic stimuli and constrictor agonists. In doing so, CO of vascular origin may contribute to the implementation of antihypertensive mechanisms. Carbon monoxide produced in central nervous system structures, for example, the nucleus tractus solitarii, also appears to support a blood pressure-lowering mechanism linked to inhibitory modulation of baroreceptor reflex activity.
Background: Early identification of patients at high risk of progression to severe COVID-19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2-infected patients. Methods: Prospective observational study enrolling adult patients with confirmed COVID-19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28-day all-cause mortality and severe COVID-19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints. Results: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28-day mortality rate was of 14.1%.
Objectives
Thromboinflammation, resulting from a complex interaction between trombocytopathy, coagulopathy and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system dysruption leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients.
Methods
Prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival to emergency department. The primary endpoint was 90-day mortality. Area under the curve (AUC) and Cox regression analysis were used to assess its discriminatory ability and association with the endpoint.
Results
A total of 359 patients were enrolled and 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cut-off of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including 11 potential confounders, were a independent predictor of 90-day mortality (HR: 0.162 [95% CI: 0.043-0.480])
Conclusions
Our data confirms that MR-proADM has a role for mid-term prognosis of COVID-19 patients and might assist to physicians for risk stratification.
Objective
Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients.
Methods
This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission.
Results
Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L;
p
< 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L;
p
= 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068).
Conclusion
Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00011-021-01516-4.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.