Adrenomedullin in COVID-19 induced endotheliitis

Wilson, Darius Cameron; Schefold, Joerg C.; Baldirà, Jaume; Spinetti, Thibaud; Saeed, Kordo; Elke, Gunnar

doi:10.1186/s13054-020-03151-7

Cited by 31 publications

(36 citation statements)

References 5 publications

(7 reference statements)

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“…Adrenomedullin is another possible biomarker for COVID-19 prognosis, as it plays a key role in reducing vascular (hyper) permeability and promoting endothelial stability and integrity following severe infection (Wilson et al, 2020). Indeed, recent studies have suggested that COVID-19 induced endothelial dysfunction and damage could be the explanation for the development of organ dysfunction and edema, resulting in impaired vascular blood flow, coagulation and leakage (Varga et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin as potential supplementary nutraceutical agent in COVID-19 patients:in vitroandin vivopreliminary evidences

Campione

Lanna

Cosio

et al. 2020

Preprint

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The current treatments against SARS-CoV-2 have proved so far inadequate. A potent antiviral drug is yet to be discovered. Lactoferrin, a multifunctional glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-Cov-2. We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. Lactoferrin induced an early viral clearance and a fast clinical symptoms recovery in addition to a statistically significant reduction of D-Dimer, Interleukin-6 and ferritin blood levels. The antiviral activity of lactoferrin related to its binding to SARS-CoV-2 and cells and protein-protein docking methods, provided the direct recognition between lactoferrin and spike S, thus hindering the spike S attachment to the human ACE2 receptor and consequently virus entering into the cells. Lactoferrin can be used as a safe and efficacious natural agent to prevent and treat COVID-19 infection.

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Section: Discussionmentioning

confidence: 99%

Lactoferrin as potential supplementary nutraceutical agent in COVID-19 patients:in vitroandin vivopreliminary evidences

Campione

Lanna

Cosio

et al. 2020

Preprint

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“…Since the virus-induced endothelial dysfunction is a possible contributing factor to the evolution of COVID-19 infection [ 4 ], the need to evaluate the role of Adrenomedullin (ADM) has been recently highlighted [ 5 ]. ADM is a multipotent regulatory peptide with a number of biological activities—vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator—widely expressed throughout the body, including bone, adrenal cortex, kidney, lung, blood vessels and heart.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: An observational prospective study

Montrucchio

Sales

Rumbolo³

et al. 2021

PLoS ONE

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Objective To test the effectiveness of mid-regional pro-adrenomedullin (MR-proADM) in comparison to C-reactive protein (CRP), procalcitonin (PCT), D-dimer, lactate dehydrogenase (LDH) in predicting mortality in COVID-19-ICU-patients. Methods All consecutive COVID-19 adult patients admitted between March and June 2020 to the ICU of a referral, university hospital in Northern-Italy were enrolled. MR-proADM and routine laboratory test were measured within 48 hours from ICU admission, on day 3, 7 and 14. Survival curves difference with MR-proADM cut-off set to 1.8 nmol/L were tested using log-rank test. Predictive ability was compared using area under the curve and 95% confidence interval of different receiver-operating characteristics curves. Results 57 patients were enrolled. ICU and overall mortality were 54.4%. At admission, lymphocytopenia was present in 86% of patients; increased D-dimer and CRP levels were found in 84.2% and 87.7% of patients respectively, while PCT values > 0.5 μg/L were observed in 47.4% of patients. MR-proADM, CRP and LDH were significantly different between surviving and non-surviving patients and over time, while PCT, D-dimer and NT-pro-BNP did not show any difference between the groups and over time; lymphocytes were different between surviving and non-surviving patients only. MR-proADM was higher in dying patients (2.65±2.33vs1.18±0.47, p<0.001) and a higher mortality characterized patients with MR-proADM >1.8 nmol/L (p = 0.016). The logistic regression model adjusted for age, gender, cardiovascular disease, diabetes mellitus and PCT values confirmed an odds ratio = 10.3 [95%CI:1.9–53.6] (p = 0.006) for MR-proADM >1.8 nmol/L and = 22.2 [95%CI:1.6–316.9] (p = 0.022) for cardiovascular disease. Overall, MR-proADM had the best predictive ability (AUC = 0.85 [95%CI:0.78–0.90]). Conclusions In COVID-19 ICU-patients, MR-proADM seems to have constantly higher values in non-survivor patients and predict mortality more precisely than other biomarkers. Repeated MR-proADM measurement may support a rapid and effective decision-making. Further studies are needed to better explain the mechanisms responsible of the increase in MR-proADM in COVID-19 patients.

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“…Although severe coronavirus disease (COVID-19) shares some clinical features of sepsis (e.g., endothelial barrier dysfunction [ 2 ]), it is not known whether pathophysiological pathways of COVID-19 resemble those of sepsis [ 2 , 3 ]. To our knowledge, this is the first study to evaluate ADM in context of COVID-19 [ 4 ].…”

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confidence: 99%

RNA-expression of adrenomedullin is increased in patients with severe COVID-19

et al. 2020

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Adrenomedullin (ADM) is a peptide hormone with vasodilatory effects and involved in the regulation of the endothelial barrier function. Previous research found increased ADM plasma levels in patients with sepsis and ADM levels correlated with disease severity and mortality in sepsis [1]. Although severe coronavirus disease (COVID-19) shares some clinical features of sepsis (e.g., endothelial barrier dysfunction [2]), it is not known whether pathophysiological pathways of COVID-19 resemble those of sepsis [2, 3]. To our knowledge, this is the first study to evaluate ADM in context of COVID-19 [4]. We present here data regarding ADM in patients with COVID-19. Starting from March 2020, we included 45 adult patients presenting with signs of respiratory infection (cough and/or fever) to the Emergency Department in this ongoing study. The study was approved by the ethics committee of the University of Regensburg. Each individual provided written informed consent prior to inclusion. SARS-CoV-2 infection status was evaluated by PCR analysis mainly using throat rinse water (or less frequently nasopharyngeal swabs). Patients were classified as COVID-19 positive (PCR positive for SARS-CoV-2 and signs of respiratory infection) or control (other viral or bacterial respiratory infection). Whole blood was drawn by venipuncture and lysed in Trifast (Ambion) buffer solution. Further, RNA expression analysis of ADM in whole blood was performed using qPCR and normalized to GAPDH as housekeeper

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Adrenomedullin in COVID-19 induced endotheliitis

Cited by 31 publications

References 5 publications

Lactoferrin as potential supplementary nutraceutical agent in COVID-19 patients:in vitroandin vivopreliminary evidences

Lactoferrin as potential supplementary nutraceutical agent in COVID-19 patients:in vitroandin vivopreliminary evidences

Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: An observational prospective study

RNA-expression of adrenomedullin is increased in patients with severe COVID-19

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