COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure

Marchetti, Monia

doi:10.1007/s00277-020-04138-8

Cited by 111 publications

(114 citation statements)

References 85 publications

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“…Troponin elevation three times the upper reference limit is known to be associated with worse in-hospital outcomes in COVID-19 patients 19,20 . It remains unclear whether the rise in cardiac biomarkers is related to viral myocarditis 5,6 or plaque rupture secondary to virus-induced inflammatory response [29][30][31] or a type 1 AMI. In this cohort of suspected type 1 myocardial infarction, there was a low prevalence of non-obstructive coronary disease and the angiographic characteristics and procedural management of the COVID-19 ACS were similar to the non COVID-19 ACS group.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Outcomes of COVID-19 Positive Acute Coronary Syndrome Patients; a multisource Electronic Healthcare Records Study from England

Rashid

Curzen

et al. 2020

Preprint

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Background: Patients with underlying cardiovascular disease and Coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality. However, there is limited information on management and outcomes of patients presenting with acute coronary syndrome (ACS) and concomitant COVID19 infection. Objectives: This multisource national analysis of live data from England was designed to characterise the presenting profile and outcomes of patients hospitalized with ACS and COVID-19 infection. Methods: Multisource data from all acute NHS hospital in England was linked to study the characteristics and outcomes of patients hospitalized with COVID-19 ACS compared to non COVID-19 ACS patients. Hierarchical multilevel models were constructed to study the association between COVID19 ACS and in-hospital and 30-day mortality. Results: Between 1st March 2020 and 31st May 2020, 517 (4.0%) were admitted with COVID- 19 ACS from a total of 12,958 ACS patients. COVID-19 ACS patients were generally older, BAME ethnicity, more comorbid and had unfavourable presenting characteristics compared to non-COVID-19 ACS patients. They were less likely to receive invasive coronary strategy in the form of coronary angiography (67.7% vs 81.0%), PCI (30.2% vs 53.9%), dual antiplatelet medication 76.3% vs 88.0%), and other important secondary medication. Patients with COVID-19 ACS had higher in-hospital (aOR 3.27 95%CI 2.41-4.42) and 30-day mortality (aOR 6.53 95%CI 5.1-8.36) compared to non COVID-19 ACS group. Conclusion: COVID-19 infection is prevalent but less frequent in the patients hospitalized with ACS in England. Presence of COVID-19 infection in patients with ACS is associated with significant mortality hazard.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Outcomes of COVID-19 Positive Acute Coronary Syndrome Patients; a multisource Electronic Healthcare Records Study from England

Rashid

Curzen

et al. 2020

Preprint

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“…Furthermore, the possible effect of the HIF-1α on the COVID-19 pathogenesis and ARDS symptoms in patients can be explained through its relevant role in other component of the immune system including the complement system [ 67 ]. According to previous studies, C3a and also C5a fractions of complement system have important roles in the pathogenesis of the infection related-lung injury.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm

2020

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COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in the end of 2019 and was rapidly spread in most countries. This respiratory virus has different symptoms from moderate to severe, and results in lung pneumonia following acute respiratory distress syndrome (ARDS) and patient’s death in severe cases. ARDS is a severe form of acute lung injury that is caused by high inflammatory response of the innate immunity cells. Hypoxia is the common feature in the inflammatory sites with having various impacts on this condition by induction of some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates some important cellular processes including cell proliferation, metabolism and angiogenesis. Furthermore, this factor is activated during the immune responses and plays important roles in the inflammation site by inducing pro-inflammatory cytokines production through immune cells. So, in this study the possible effect of the HIF-1α on the COVID-19 pathogenesis with emphasizes on its role on innate immunity response has been discussed.

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“…Patients with severe COVID-19 might experience cytokine release syndrome, and several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs), therefore, JAK inhibition presents an attractive therapeutic strategy for CRS [ 59 ]. What’s more, it has been reported that complement and HIF-1 are potential pathways of damage and targets for the cure of COVID-19-driven endothelial damage [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

Huang

Zheng

et al. 2020

BioData Mining

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Background Chinese medicine Toujie Quwen granule (TJQW) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases by relieving symptoms, slowing the progression of the disease, and boosting the recovery of patients. But the bioactive compounds and potential mechanisms of TJQW for COVID-19 prevention and treatment are unclear. This study aimed to explore the potential therapeutic mechanism of TJQW in coronavirus disease 2019 (COVID-19) based on an integrated network pharmacology approach. Methods TCMSP were used to search and screen the active ingredients in TJQW. The Swiss TargetPrediction was used to predict the potential targets of active ingredients. Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. Venn diagram was created to show correlative targets of TJQW against COVID-19. Cytoscape was used to construct a “drug-active ingredient-potential target” network, STRING were used to construct protein-protein interaction network, and cytoHubba performed network topology analysis. Enrichment of biological functions and signaling pathways of core targets was performed by using the clusterProfiler package in R software and ClueGO with CluePedia plugins in Cytoscape. Results A total of 156 active ingredients were obtained through oral bioavailability and drug-likeness screenings. Two hundred twenty-seven potential targets of TJQW were related to COVID-19. The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE. Based on that, we obtained 19 key active ingredients: umbelliprenin, quercetin, kaempferol, luteolin, praeruptorin E, stigmasterol, and oroxylin A. And the enrichment analysis obtained multiple related gene ontology functions and signaling pathways. Lastly, we constructed a key network of “drug-component-target-biological process-signaling pathway”. Our findings suggested that TJQW treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including regulation of inflammatory response, viral process, neutrophil mediated immunity, PI3K-Akt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Complement and coagulation cascades, and HIF-1 signaling pathway. Conclusions Our study uncovered the pharmacological mechanism underlying TJQW treatment for COVID-19. These results should benefit efforts for people around the world to gain more knowledge about Chinese medicine TJQW in the treatment of this vicious epidemic COVID-19, and help to address this pressing problem currently facing the world.

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COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure

Cited by 111 publications

References 85 publications

Clinical Characteristics and Outcomes of COVID-19 Positive Acute Coronary Syndrome Patients; a multisource Electronic Healthcare Records Study from England

Clinical Characteristics and Outcomes of COVID-19 Positive Acute Coronary Syndrome Patients; a multisource Electronic Healthcare Records Study from England

Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm

Therapeutic mechanism of Toujie Quwen granules in COVID-19 based on network pharmacology

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