Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Polidoro, Rafael B.; Hagan, Robert S.; Santiago, Roberta De Santis; Schmidt, Nathan W.

doi:10.3389/fimmu.2020.01626

Cited by 164 publications

(167 citation statements)

References 105 publications

(145 reference statements)

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“…These conditions are characterized by increased permeability of lung capillaries and the entry of solutes and fluids into the alveolar lumen 70 (Box 3 ). In addition to increasing pulmonary oedema and facilitating leukocyte emigration, elevated vascular permeability may potentially facilitate SARS-CoV-2 dissemination to the circulation 71 .…”

Section: Leukocytes Recruited To Infected Lungsmentioning

confidence: 99%

“…Reactive oxygen species, locally secreted by these aggregates or by entrapped neutrophils 70 , can also increase vascular permeability. In addition, in severe influenza virus infection and likely also in SARS-CoV-2 infection, VEGF 197 , tumour necrosis factor (TNF), IL-1β, NO and bradykinin, secreted by infected epithelial cells, by the endothelial cells lining the pulmonary vessels (primarily capillaries) and by both resident and recruited leukocytes 71 , may each increase lung vessel permeability and injury by reducing the integrity of VE-cadherin assemblies and driving endothelial contractility (reviewed in refs 23 , 198 ).…”

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confidence: 99%

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Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.

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Section: Leukocytes Recruited To Infected Lungsmentioning

confidence: 99%

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confidence: 99%

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

et al. 2020

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“…Discussion SARS-CoV-2 infection could cause acute lung injury, and one of the important reasons is dysregulation of the immune system in the lung 8,9 that results in the release of a large number of in ammatory factors and forms "cytokine storm" 10 . In this study, we found that SARS-CoV-2 infection of macrophages and dendritic cells would promote the expression of abundant cytokines and chemokines by analyzing the GEO database (GSE155106).…”

Section: Sars-cov-2 N Protein Induces Mice Lung Injury Via Activatingmentioning

confidence: 99%

“…Therefore, the pathogenesis of SARS-CoV-2 is an urgent scienti c problem to be explored. SARS-CoV-2 infects human lung through the respiratory system and thus cause severe in ammatory responses 8,9 . Signi cant evidence demonstrated that a dysregulated innate immune response contributes to the clinical presentation of patients with severe COVID-19 10 .…”

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confidence: 99%

SARS-CoV-2 N promotes the NLRP3 inflammasome activation to induce hyperinflammation

Pan¹,

Shen

et al. 2020

Preprint

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Excessive inflammatory responses induced upon SARS-CoV-2 infection interlocks with severe symptoms and acute lung injury in patients with Severe Coronavirus Disease 2019 (COVID-19). Revealing the mechanism underlying the control of SARS-CoV-2-triggered immune-inflammatory responses would help us to understand the pathological process and guide clinical treatment. However, the effect of the NLRP3 inflammasome on regulating SARS-CoV-2-induced inflammatory responses has not been reported. Here, we revealed a distinct mechanism by which SARS-CoV-2 nucleocapsid (N) protein promotes the NLRP3 inflammasome activation to induce hyperinflammation. We demonstrated that N protein facilitates the maturation of proinflammatory cytokines IL-1β and IL-6 and induces proinflammatory responses in cultured cells and mice tissues. In team of molecular mechanism, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates the assemble of the inflammasome complex. More importantly, N protein aggravates lung injury, accelerated death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production were blocked by Ac-YVAD-cmk, an inhibitor of the NLRP3 inflammasome. Therefore, this study revealed a distinct mechanism by which SARS-CoV-2 N protein promotes the NLRP3 inflammasome activation and induces excessive inflammatory responses.

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“…Also, increasing lung endothelium permeability and reducing barrier protection attracts more neutrophils to the infection site through endothelial penetration (Fig. 3b ) (Polidoro et al 2020 ). This inflammatory immune response dysregulation prevents adaptive immune response activation (Manjili et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective

Lee

Choi

2021

Arch. Pharm. Res.

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The novel beta coronavirus (SARS-CoV-2, designated as COVID-19) that is responsible for severe acute respiratory syndrome has devastated the global economy and health care system. Since COVID-19 changed the definition of "normal" in ordinary life around the world, the development of effective therapeutics and preventive measures is desperately needed to fight SARS-CoV-2 infection and restore normalcy. A clear understanding of COVID-19 pathogenesis is crucial in providing the scientific rationale necessary to develop anti-COVID19 drugs and vaccines. According to the most recently published literature, COVID-19 pathogenesis was postulated to occur in three sequential phases: pulmonary, proinflammatory, and prothrombic. Herein, virus-host interactions, potential pathogenic mechanisms, and clinical manifestations are described for each phase. Additionally, based on this pathogenesis model, various therapeutic strategies involving current clinical trials are presented with an explanation of their modes of action and example drugs. This review is a thorough, updated summary of COVID-19 pathogenesis and the therapeutic options available for this disease. Keywords Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) • Coronavirus disease 2019 (COVID-19) • Renin-angiotensin system (RAS) • Angiotensin-converting enzyme 2 (ACE2) • ACE2 deficiency • Acute respiratory distress syndrome (ARDS) • Acute lung injury (ALI) • Cytokine storm • Thrombosis • Coagulopathy • Multi-organ failure (MOF)

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Overview: Systemic Inflammatory Response Derived From Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19

Cited by 164 publications

References 105 publications

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

Leukocyte trafficking to the lungs and beyond: lessons from influenza for COVID-19

SARS-CoV-2 N promotes the NLRP3 inflammasome activation to induce hyperinflammation

Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective

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