scholarly journals Single Cell RNA Sequencing Identifies Type I Interferon Signaling and Reduced Suppressor of Cytokine Signaling 3 Expression in Monocytes of Acute Respiratory Distress Syndrome Patients

2020 ◽  
Author(s):  
B.R. Rosborough ◽  
Y. Jiang ◽  
J. Chen ◽  
G. Kitsios ◽  
B.J. McVerry ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Type I Interferon ◽  
Cytokine Signaling ◽  
Type I ◽  
Interferon Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Single Cell Rna Sequencing

scholarly journals Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

BMJ ◽  
2020 ◽  
pp. m1091 ◽  
Author(s):  
Tao Chen ◽  
Di Wu ◽  
Huilong Chen ◽  
Weiming Yan ◽  
Danlei Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Clinical Characteristics ◽  
Distress Syndrome ◽  
Cardiac Injury ◽  
Cardiac Complications ◽  
Type I

Abstract Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

scholarly journals Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression

2020 ◽  
Vol 21 (17) ◽  
pp. 6244
Author(s):  
Amira Mohammed ◽  
Hasan F.K. Alghetaa ◽  
Kathryn Miranda ◽  
Kiesha Wilson ◽  
Narendra P. Singh ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Single Cell ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Distress Syndrome ◽  
Elevated Serum ◽  
Cytokine Storm ◽  
Single Cell Rna Sequencing

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.

scholarly journals Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Fabienne Venet ◽  
◽  
Martin Cour ◽  
Thomas Rimmelé ◽  
Sebastien Viel ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Type I ◽  
Immune Profile ◽  
Icu Admission ◽  
Over Time

Abstract Background Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. Methods We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. Results ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. Conclusions Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.

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 The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS)

Leukemia ◽  
2021 ◽  
Author(s):  
Andreas Neubauer ◽  
Johannes Johow ◽  
Elisabeth Mack ◽  
Andreas Burchert ◽  
Damaris Meyn ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Kinase Inhibitor ◽  
Invasive Mechanical Ventilation ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Janus Kinase Inhibitor

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019), which is associated with high morbidity and mortality, especially in elder patients. Acute respiratory distress syndrome (ARDS) is a life-threatening complication of COVID-19 and has been linked with severe hyperinflammation. Dexamethasone has emerged as standard of care for COVID-19 associated respiratory failure. In a non-randomized prospective phase II multi-center study, we asked whether targeted inhibition of Janus kinase-mediated cytokine signaling using ruxolitinib is feasible and efficacious in SARS-CoV-2- induced ARDS with hyperinflammation. Sixteen SARS-CoV-2 infected patients requiring invasive mechanical ventilation for ARDS were treated with ruxolitinib in addition to standard treatment. Ruxolitinib treatment was well tolerated and 13 patients survived at least the first 28 days on treatment, which was the primary endpoint of the trial. Immediate start of ruxolitinib after deterioration was associated with improved outcome, as was a lymphocyte-to-neutrophils ratio above 0.07. Together, treatment with the janus-kinase inhibitor ruxolitinib is feasible and might be efficacious in COVID-19 induced ARDS patients requiring invasive mechanical ventilation. The trial has been registered under EudraCT-No.: 2020-001732-10 and NCT04359290.

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