Cardiovascular signatures of COVID-19 predict mortality and identify barrier stabilizing therapies

Gustafson, Dakota; Ngai, Michelle; Wu, Runye; Hou, Huayun; Schöffel, Alice Carvalhal; Erice, Clara; Mandla, Serena; Billia, Filio; Wilson, Michael D.; Radišić, Milica; Fan, Eddy; Trahtemberg, Uriel; McIntosh, Chris; Fan, Chun‐Po Steve; Santos, Claudia C Dos; Kain, Kevin C.; Hanneman, Kate; Thavendiranathan, Paaladinesh; Fish, Jason E.; Howe, Kathryn L.

doi:10.1016/j.ebiom.2022.103982

Cited by 17 publications

(16 citation statements)

References 121 publications

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“…There was a similar effect on permeability when HMVECs were exposed to non–COVID-19 sera from patients with acute illness. The presence of an indirect effect of circulating COVID-19 mediators on endothelial permeability has been previously demonstrated ( 11 ). The sera-induced HMVEC permeability effect observed by Joffre and colleagues was modest when compared with the effect of direct viral infection, and similar to the effect seen with non–COVID-19 sera.…”

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confidence: 84%

Insights into Endotheliopathy in COVID-19

Filbin

2022

Am J Respir Crit Care Med

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Severe COVID-19 is characterized by a disruption of barrier function between the pulmonary circulation and alveoli, leading to characteristic alveolar infiltrates, hypoxemia, and in the worst case acute respiratory distress syndrome (ARDS) (1). Endothelial integrity plays an important role in maintaining the pulmonary capillary-alveolar barrier. Autopsy studies have shown that severe COVID-19 is associated with endothelial cell damage, perivascular inflammatory cell infiltration, with interstitial edema and alveolar space fluid consolidation (2). Clinical studies measuring circulating endothelial biomarkers support the hypothesis that endothelial dysfunction is an underlying factor in COVID-19 pathogenesis and a harbinger of poor outcome (3). Despite evidence that lung endothelial injury plays a key role in severe COVID-19, there has been relatively little translational investigation focusing on pulmonary vascular endothelium and its response to SARS-CoV-2 infection. Joffre et al., here, employed an ex vivo model of non-COVID-19 cadaveric primary human lung microvascular endothelial cells (HMVECs) from 6 non-COVID-19 donors to systematically study endothelial responses to live SARS-CoV-2 virus, inactivated virus, spike protein, and sera from acutely-ill COVID-19 patients (4). Authors demonstrated that live SARS-CoV-2 virus exposed to HMVECs directly infects and replicates within endothelial cells. This is consistent with a prior study of viral infection introduced in bioengineered human sinusoidal cells (5), and autopsy studies that have shown intracellular virus within capillary endothelium (2), Joffre's findings support a hypothesis that pulmonary capillary endothelia provide an environment for viral replication, facilitating viral access to the systemic circulation.Authors further demonstrated that SARS-CoV-2 infected HMVECs exhibit increased endothelial permeability as inferred using transepithelial resistance (TER). The increase in permeability was particularly sizable in 3 of the 6 HMVEC donors, although significant in all. Thus, direct pulmonary endothelial cell infection contributes to increased endothelial barrier permeability and may play a role in exacerbating pulmonary interstitial edema and transmigration of inflammatory

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confidence: 84%

Insights into Endotheliopathy in COVID-19

Filbin

2022

Am J Respir Crit Care Med

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“…Differences in clinical features between the high and low PAR groups were detected using the chi-squared test or Student's t -test according to the data type. Because machine learning methods could help to handle nonlinear and high-order terms automatically and improve the predictive performance of clinical model [ 14 , 15 ], the support vector machine algorithm, along with LASSO Cox regression, was then applied to identify significant metrics associated with 28-day mortality in the test cohort, and only informative metrics with P < 0.05 were finally included in the construction of the survival nomogram. Receiver operating curve (ROC) along with sensitivity and specificity was measured to assess the predictive performances of PAR and survival nomogram.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Utility of Platelet-to-Albumin Ratio among Critically Ill Patients with Colorectal Cancer: A Propensity Score Matching Study

Wang

et al. 2022

Journal of Oncology

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The platelet-to-albumin ratio (PAR) was developed to evaluate inflammatory and nutritional status among patients. The primary goal of the current study was to gain insight into the prognostic role of PAR in critically ill patients with colorectal cancer (CRC). The secondary aim was to develop and verify a clinical model including PAR for the prediction of 28-day mortality. This observational, multicenter study used data from the Medical Information Mart for Intensive Care (MIMIC) IV, e-ICU databases, and Union cohort. Data from 776 critically ill patients with CRC were from the e-ICU database, 219 from the MIMC-IV database, and 135 from the Wuhan Union Hospital. Propensity score matching (PSM) analysis, along with inverse probability treatment weighting, was used to control the influence of confounding factors. Support vector machine (SVM) and LASSO Cox models were then applied to identify significant metrics associated with 28-day mortality in the test cohort. Receiver operating curve (ROC) analysis, along with sensitivity and specificity, was measured to assess the predictive performances of PAR and the survival nomogram. The threshold value for PAR was 8.6, and patients with high PAR (≥8.6) experienced higher 28-day mortality compared to those with low PAR (<8.6). ROC curve analyses revealed that the discriminative ability of PAR was better than platelet count and albumin alone. LASSO Cox regression along with SVM identified six significant metrics associated with 28-day mortality in critically ill patients with CRC, including PAR. The C-index of the critically ill CRC nomogram was 0.802 (0.744–0.859) in the e-ICU training cohort, 0.839 (0.779–0.899) in the e-ICU validation cohort, 0.787 (0.695–0.879) in the MIMIC-IV cohort, and 0.767 (0.703–0.831) in the Union cohort. PAR is a simple score that combines inflammatory and nutritional status. PAR was a reliable index to predict short-term survival outcome of critically ill patients with CRC. Moreover, a clinical nomogram incorporating PAR exhibited satisfactory performance for predicting 28-day mortality of critically ill patients with CRC.

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“…In patients hospitalized with COVID-19, Ang-2, IL6, and MPO were associated with mortality, but without conclusive evidence of specificity for COVID-19. In addition, 207 differentially expressed miRNAs were found between survivors and non-survivors in the severe COVID-19 group, including miRNA pathways for platelet activation, extracellular matrix-receptor interactions, Ras, and ErbB2 [ 194 ]. Differently from non-COVID-19 ARDS, patients with COVID-19 showed better outcomes using corticosteroids.…”

Section: Omics In Ards Researchmentioning

confidence: 99%

“…It seems that the combination of biomarkers can characterize the pathophysiologic responses in patients with COVID-19 or individualize management according to the biological phenotypes. Gustafson et al [ 194 ] published a study, providing a clear example of how the incorporation of clinical data with omics should be identifying COVID-19 phenotypes and providing prognostic information. The authors confirmed that corticosteroids are useful in COVID-19 under inflammatory conditions, reinforcing the need for appropriate timing of administration and settings when designing clinical trials.…”

Section: Omics In Ards Researchmentioning

confidence: 99%

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

et al. 2022

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In the last decade, research on acute respiratory distress syndrome (ARDS) has made considerable progress. However, ARDS remains a leading cause of mortality in the intensive care unit. ARDS presents distinct subphenotypes with different clinical and biological features. The pathophysiologic mechanisms of ARDS may contribute to the biological variability and partially explain why some pharmacologic therapies for ARDS have failed to improve patient outcomes. Therefore, identifying ARDS variability and heterogeneity might be a key strategy for finding effective treatments. Research involving studies on biomarkers and genomic, metabolomic, and proteomic technologies is increasing. These new approaches, which are dedicated to the identification and quantitative analysis of components from biological matrixes, may help differentiate between different types of damage and predict clinical outcome and risk. Omics technologies offer a new opportunity for the development of diagnostic tools and personalized therapy in ARDS. This narrative review assesses recent evidence regarding genomics, proteomics, and metabolomics in ARDS research.

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Cardiovascular signatures of COVID-19 predict mortality and identify barrier stabilizing therapies

Cited by 17 publications

References 121 publications

Insights into Endotheliopathy in COVID-19

Insights into Endotheliopathy in COVID-19

Prognostic Utility of Platelet-to-Albumin Ratio among Critically Ill Patients with Colorectal Cancer: A Propensity Score Matching Study

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

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