scholarly journals Intravenous Mesenchymal Stem Cells in Extracorporeal Oxygenation Patients with Severe COVID-19 Acute Respiratory Distress Syndrome

2020 ◽  
Author(s):  
Sunjay Kaushal ◽  
Aisha Khan ◽  
Kristopher Deatrick ◽  
Derek K. Ng ◽  
Abigail Snyder ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Viral Clearance ◽  
Spike Protein ◽  
Critically Ill Patient ◽  
Control Group

BackgroundThere is an ongoing critical need to improve therapeutic strategies for COVID-19 pneumonia, particularly in the most severely affected patients. Adult mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill patients with acute respiratory syndrome SARS-COV-2 infection, but clinical data supporting efficacy are lacking.MethodsWe conducted a case-control study of critically ill patients with laboratory-confirmed COVID-19, severe acute respiratory distress syndrome (ARDS). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance.FindingsMSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma did not clear COVID-19 IgG over the same time frame.InterpretationTogether these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.

scholarly journals Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia

2021 ◽  
Vol 10 (13) ◽  
pp. 2935
Author(s):  
Jose Bordon ◽  
Ozan Akca ◽  
Stephen Furmanek ◽  
Rodrigo Silva Cavallazzi ◽  
Sally Suliman ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Critical Illness ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Invasive Mechanical Ventilation ◽  
Overall Mortality

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.

scholarly journals Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis

2020 ◽  
Vol 46 (6) ◽  
pp. 1222-1231 ◽  
Author(s):  
Catherine L. Auriemma ◽  
Hanjing Zhuo ◽  
Kevin Delucchi ◽  
Thomas Deiss ◽  
Tom Liu ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Attributable Mortality

scholarly journals Genomics and the Acute Respiratory Distress Syndrome: Current and Future Directions

2019 ◽  
Vol 20 (16) ◽  
pp. 4004 ◽  
Author(s):  
Hernández-Beeftink ◽  
Guillen-Guio ◽  
Villar ◽  
Flores
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Genetic Factors ◽  
Distress Syndrome ◽  
New Therapies ◽  
Genetic Predictors ◽  
Prognostic Stratification

The excessive hospital mortality associated with acute respiratory distress syndrome (ARDS) in adults mandates an urgent need for developing new therapies and tools for the early risk assessment of these patients. ARDS is a heterogeneous syndrome with multiple different pathogenetic processes contributing differently in different patients depending on clinical as well as genetic factors. Identifying genetic-based biomarkers holds the promise for establishing effective predictive and prognostic stratification methods and for targeting new therapies to improve ARDS outcomes. Here we provide an updated review of the available evidence supporting the presence of genetic factors that are predictive of ARDS development and of fatal outcomes in adult critically ill patients and that have been identified by applying different genomic and genetic approaches. We also introduce other incipient genomics approximations, such as admixture mapping, metagenomics and genome sequencing, among others, that will allow to boost this knowledge and likely reveal new genetic predictors of ARDS susceptibility and prognosis among critically ill patients.

scholarly journals Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

2017 ◽  
Vol 2 (2) ◽  
pp. 1-12 ◽  
Author(s):  
Ruxana T. Sadikot ◽  
Arun V. Kolanjiyil ◽  
Clement Kleinstreuer ◽  
Israel Rubinstein
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Mode Of Delivery ◽  
Heterogenous Group

Acute lung injury and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients that continues to have high mortality. Despite the increased understanding of the molecular pathogenesis of ARDS, specific targeted treatments for ARDS have yet to be developed. ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Multiple promising targets have been identified that could lead to the development of potential therapies for ARDS; however, they have been limited because of difficulty with the mode of delivery, especially in critically ill patients. Nanobiotechnology is the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmacodynamics of agents, allowing an increase in the biodistribution of therapeutic agents to target organs and resulting in improved efficacy with reduction in drug toxicity. Although attractive, delivering nanomedicine to lungs can be challenging as it requires sophisticated systems. Here we review the potential of novel nanomedicine approaches that may prove to be therapeutically beneficial for the treatment of this devastating condition.

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