High value of mid‐regional proadrenomedullin in COVID‐19: A marker of widespread endothelial damage, disease severity, and mortality

Abstract

The widespread endothelial damage due to severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi‐organs dysfunction. The aim of this study was to evaluate the role of Mid‐regional proAdrenomedullin (MR‐proADM) as a marker of SARS CoV2‐related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS‐CoV2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR‐proADM cut‐off values for ARDS development and mortality prediction were 3.04 nmol/L and 2 nmol/L, respectively. Patients presenting with MR‐proADM values ≥ 2 nmol/L showed a significantly higher mortality risk. In conclusion, MR‐proADM values ≥ 2 nmol/l identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach. This article is protected by copyright. All rights reserved.

MR‐proADM as marker of endotheliitis predicts COVID‐19 severity

“…To our knowledge, only a previous study has analysed the prognostic value of MR-proADM in COVID-19. Spoto et al 40 have recently reported a ROC AUC for 28-day mortality of 0.89 in 69 patients, similar to that reported in our study (0.905) in a larger sample. Further, there were substantial differences regarding baseline characteristics between the populations of both studies.…”

“…This disagreement is likely due to differences in both study population characteristics. Hence, Spoto et al cohort 40 included older patients than those in our study (79 years vs . 66 years), with a higher incidence of comorbidities such as cardiovascular disease (68.1% vs .…”

Immunothrombotic dysregulation in chagas disease and COVID-19: a comparative study of anticoagulation

“…[ 122 ] A study of Post-acute COVID-19 syndrome in Bergamo, Italy, found hypercoagulation in 17% of patients with D-dimer values that increased more than two times above 500 ng/mL [ 123 ]. In addition, ischemic cardiovascular events are increasing in COVID-19 [ 124 ], myocardial injury and elevated troponin levels are also reported [ 125 ] Inflammation and vascular leakage Trypomastigotes boost their infectivity through activation of the mast cell/kallikrein-kinin system pathway, resulting in inflammatory oedema [ 126 ] At the site of infection by T cruzi , C5a, and bradykinin are released and modulate innate and adaptive immunity, inflammation, and plasma leakage [ 127 ] The severity of COVID-19 is related to increased inflammation markers such as C-reactive protein (CRP), interleukin-6, nuclear factor kappa B (NFκB), and tumour necrosis factor-alpha (TNFα) as well as multiorgan failure [ 128 ] Mid-Regional proAdrenomedullin (MR-proADM), a marker of endothelial integrity and vascular leakage, is also related to severity and mortality in COVID-19 [ 129 ] During COVID-19, inflammation, vasodilation, hypotension, and plasma leakage may be due to the bradykinin system, in particular des-Arg9-BK, which acts on Bradykinin 1 (B1) receptor [ 130 ] …”

“…Mid-Regional proAdrenomedullin (MR-proADM), a marker of endothelial integrity and vascular leakage, is also related to severity and mortality in COVID-19 [ 129 ]…”

Pooled analysis of mid-regional pro-adrenomedullin values in COVID-19 patients with critical illness

“…No significant disagreement emerged between the two reviewers. Six studies were thus finally included in pooled analysis, totaling 487 COVID-19 patients, 159 (32.6%) with critical illness, as summarized in Table 1 [ 7 – 12 ]. All included studies were cross sectional investigations, three conducted in Italy, while the others were located in Germany, Russia and Switzerland.…”