COVID-19: the key role of pulmonary capillary leakage. An observational cohort study

Wu, Maddalena Alessandra; Fossali, Tommaso; Pandolfi, Laura; Carsana, Luca; Ottolina, Davide; Frangipane, Vanessa; Rech, Roberto; Tosoni, Antonella; Agarossi, Andrea; Cogliati, Chiara; Meloni, Federica; Marchini, Beatrice; Nebuloni, Manuela; Catena, E; Colombo, Riccardo

doi:10.1101/2020.05.17.20104877

Cited by 11 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, electron microscopy of post-mortem lung tissue reveals extensive opening of junctional complexes. Hyperalbuminemia in severe COVID-19 patients, consistent with vascular permeability and capillary leakage, is strongly associated with mortality ( Wu M. A. et al., 2020 ).…”

Section: Adhesion and Tissue Retention Of Inflammatory Leukocytesmentioning

confidence: 99%

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

2020

View full text Add to dashboard Cite

With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-l-dependent epithelial defense. Differentiation of non-classic pathogenic T-cells and pro-inflammatory intermediate monocytes contributes to a skewed inflammatory profile, mediated by membrane-bound immune receptor subtypes (e.g., FcgRIIA) and downstream signaling pathways (e.g., NF-kB p65 and p38 MAPK), followed by chemotactic infiltration of monocyte-derived macrophages and neutrophils into lung tissue. Endothelial barrier degradation and capillary leakage contribute to alveolar cell damage. Inflammatory cytokine release, delayed neutrophil apoptosis, and NETosis contribute to pulmonary thrombosis and cytokine storm. These mechanisms are concordant with observed clinical markers in COVID-19, including high expression of inflammatory cytokines on the TNF-a/ IL-6 axis, elevated neutrophil-to-lymphocyte ratio (NLR), diffuse alveolar damage via cell apoptosis in respiratory epithelia and vascular endothelia, elevated lactate dehydrogenase (LDH) and CRP, high production of neutrophil extracellular traps (NETs), depressed platelet count, and thrombosis. Although certain elements are likely to be revised as new findings emerge, the proposed pathway suggests multiple points of investigation for potential therapeutic interventions. Initial candidate interventions include prophylaxis to augment epithelial defense (e.g., AT1 receptor blockade, type III and type I interferons, melatonin, calcitriol, camostat, and lopinavir) and to reduce viral load (e.g., remdesivir, ivermectin, emetine, Abelson kinase inhibitors, dopamine D2 antagonists, and selective estrogen receptor modulators). Additional interventions focus on tempering inflammatory signaling and injury (e.g., dexamethasone, doxycycline, Ang1-7, estradiol, alpha blockers,

show abstract

Section: Adhesion and Tissue Retention Of Inflammatory Leukocytesmentioning

confidence: 99%

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

2020

View full text Add to dashboard Cite

show abstract

“…We recently reported a SARS-CoV-2-induced crisis of a patient with a 7-year history of IgG Kappa Clarkson's disease, 2 and several articles lately highlighted the role of lung capillary leakage in the pathophysiologic condition of COVID-19. 3 These data suggest that COVID-19 can induce both Clarkson's disease episodes (henceforth primary SCLS) and secondary SCLS. Several considerations must be addressed to determine the nature of the capillary-leak syndrome in the reported patient.…”

mentioning

confidence: 93%

“…We recently reported a SARS-CoV-2-induced crisis of a patient with a 7-year history of IgG Kappa Clarkson’s disease, 2 and several articles lately highlighted the role of lung capillary leakage in the pathophysiologic condition of COVID-19. 3 …”

mentioning

confidence: 99%

Clarkson’s Disease Episode or Secondary Systemic Capillary Leak-Syndrome

Chambrun

Constantin

Mathian

et al. 2021

Chest

View full text Add to dashboard Cite

“…Coronavirus disease 2019–driven endothelial damages have been documented 33,34 . Increased vascular permeability has been reported in some patients and seems to be strongly related to increased thrombosis.…”

Section: Figurementioning

confidence: 99%

Can Low‐Intensity Pulsed Ultrasound Treat Discrete Pulmonary Lesions in Patients With COVID‐19?

Prada

Cogliati

et al. 2020

J of Ultrasound Medicine

Self Cite

View full text Add to dashboard Cite

COVID-19: the key role of pulmonary capillary leakage. An observational cohort study

Cited by 11 publications

References 34 publications

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention

Clarkson’s Disease Episode or Secondary Systemic Capillary Leak-Syndrome

Can Low‐Intensity Pulsed Ultrasound Treat Discrete Pulmonary Lesions in Patients With COVID‐19?

Contact Info

Product

Resources

About