scholarly journals Tracheal Aspirate Sequencing Identifies Unique Features of Dysregulated Host Response in SARS-CoV2 Associated Acute Respiratory Distress Syndrome

2021 ◽  
Author(s):  
A. Sarma ◽  
S. Christenson ◽  
E. Mick ◽  
C. DeVoe ◽  
T. Deiss ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Host Response ◽  
Distress Syndrome ◽  
Tracheal Aspirate

scholarly journals Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection

2009 ◽  
Vol 83 (14) ◽  
pp. 7062-7074 ◽  
Author(s):  
Barry Rockx ◽  
Tracey Baas ◽  
Gregory A. Zornetzer ◽  
Bart Haagmans ◽  
Timothy Sheahan ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Host Response ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Aged Mice ◽  
Young Mice

ABSTRACT Several respiratory viruses, including influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV), produce more severe disease in the elderly, yet the molecular mechanisms governing age-related susceptibility remain poorly studied. Advanced age was significantly associated with increased SARS-related deaths, primarily due to the onset of early- and late-stage acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Infection of aged, but not young, mice with recombinant viruses bearing spike glycoproteins derived from early human or palm civet isolates resulted in death accompanied by pathological changes associated with ARDS. In aged mice, a greater number of differentially expressed genes were observed than in young mice, whose responses were significantly delayed. Differences between lethal and nonlethal virus phenotypes in aged mice could be attributed to differences in host response kinetics rather than virus kinetics. SARS-CoV infection induced a range of interferon, cytokine, and pulmonary wound-healing genes, as well as several genes associated with the onset of ARDS. Mice that died also showed unique transcriptional profiles of immune response, apoptosis, cell cycle control, and stress. Cytokines associated with ARDS were significantly upregulated in animals experiencing lung pathology and lethal disease, while the same animals experienced downregulation of the ACE2 receptor. These data suggest that the magnitude and kinetics of a disproportionately strong host innate immune response contributed to severe respiratory stress and lethality. Although the molecular mechanisms governing ARDS pathophysiology remain unknown in aged animals, these studies reveal a strategy for dissecting the genetic pathways by which SARS-CoV infection induces changes in the host response, leading to death.

scholarly journals Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther J. Nossent ◽  
Alex R. Schuurman ◽  
Tom D.Y. Reijnders ◽  
Anno Saris ◽  
Ilse Jongerius ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Growth Factors ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Complement System ◽  
Host Response ◽  
Distress Syndrome ◽  
Response Biomarkers

RationaleSystemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.ObjectivesTo evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.MethodsPaired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.Measurements and Main ResultsIn all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.ConclusionsCritically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.

scholarly journals Host-Response Subphenotypes Offer Prognostic Enrichment in Patients With or at Risk for Acute Respiratory Distress Syndrome*

2019 ◽  
Vol 47 (12) ◽  
pp. 1724-1734 ◽  
Author(s):  
Georgios D. Kitsios ◽  
Libing Yang ◽  
Dimitris V. Manatakis ◽  
Mehdi Nouraie ◽  
John Evankovich ◽  
...  
Keyword(s):  
At Risk ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Host Response ◽  
Distress Syndrome

scholarly journals Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jocelyn R. Grunwell ◽  
Susan T. Stephenson ◽  
Ahmad F. Mohammad ◽  
Kaitlin Jones ◽  
Carrie Mason ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Tracheal Aspirate ◽  
Neutrophil Extracellular Trap ◽  
Interferon Response ◽  
Type I ◽  
Elevated Expression ◽  
Extracellular Trap

Abstract Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days.

scholarly journals Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome

Thorax ◽  
2014 ◽  
Vol 69 (7) ◽  
pp. 623-629 ◽  
Author(s):  
Charlotte Summers ◽  
Nanak R Singh ◽  
Jessica F White ◽  
Iain M Mackenzie ◽  
Andrew Johnston ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Host Response ◽  
Distress Syndrome

COVID-19 – eine vaskuläre Systemerkrankung

2020 ◽  
Vol 49 (10) ◽  
pp. 418-421
Author(s):  
Christopher Werlein ◽  
Peter Braubach ◽  
Vincent Schmidt ◽  
Nicolas J. Dickgreber ◽  
Bruno Märkl ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.

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