https://www.forbes.com/sites/emilyprice/2020/10/03/thc-in-cannabis-could-help-prevent-fatal-covid-19-complications/?sh=b45d4bb409e2
https://www.athersys.com/investors/press-releases/press-release-details/2021/Report-of-Placebo-Controlled-Clinical-Trial-Evaluating-MultiStem-Cell-Therapy-for-Acute-Respiratory-Distress-Syndrome-Published-in-Intensive-Care-Medicine/default.aspx
This cohort study found that metabolic syndrome, diagnosed by the clustering of obesity, prediabetes or diabetes, hypertension, and dyslipidemia, was associated with significantly increased mortality and ARDS in a global population of hospitalized patients with COVID-19. This increased risk was cumulative, with the proportion of ARDS increasing with each added metabolic syndrome criteria.
MUST-ARDS RESULTS PUBLISHED:
https://link.springer.com/content/pdf/10.1007/s00134-021-06570-4.pdf
10.1097/MJT.0000000000001343
SUMMARY OF THE INVENTION
It is evident that patients suffering from severe COVID-19 have dysregulated hyperinflammatory responses characterized by increased T cell and monocyte/macrophage activation that contribute and may be the cause of the disease pathology. The inventors investigated whether multipotent adult progenitor cells (MAPC) have the ability to modulate uncontrolled immune responses, thereby reestablishing immune homeostasis and promoting tissue repair in virus-induced acute respiratory distress syndrome (ARDS), specifically in COVID-19-induced ARDS. The inventors used a preparation designated โMultiStemยฎ,โ which is a commercial preparation based on MAPCs that were disclosed in Jiang et ah, Nature 2002, 418:41-9. There is evidence demonstrating that MultiStemยฎ cells reduce dysregulated prolonged T cell activation and proliferation (Reading et al., J. Immunol. 2013, 190:4542-4552; Reading et al., Molecular Therapy 2015, 23(11): 1783-1793; Yang et al., Stem Cells 2017, 35:1290-1302; Carty et al., Front. Immunol. 2018, 9:645 (doi: 10.3389/fimmu.2018.00645)). Based on that the inventors considered the possibility of preventing T cell exhaustion (Walker et al., J. Neuroinflammation 2012, 9:228; Reading et al., J. Immunol. 2013, 190(9):4542-4552; Kovacsovics-Bankowski et al., Cell Immunol. 2009, 255(l-2):55-60) by administering MultiStemยฎ to patients with moderate to severe ARDS. Additionally, there are reports that MultiStemยฎ cells promote the differentiation of regulatory T cells (Walker et al., J. Neuroinflammation 2012, 9:228; Reading et al., J. Immunol. 2013, 190(9):4542-4552; Reading et al., Mol. Ther. 2015, 23(11): 1783- 1793; Yang et al., Stem Cells 2017, 35(5): 1290-1302). So the inventors considered that administering MultiStemยฎ might alleviate ARDS and drive the proliferation of AT2 cells (Mock et al., Mucosal Immunol. 2014, 7(6): 1440-1451). Furthermore, MultiStemยฎ cells have been reported to reduce monocyte/macrophage proinflammatory profile by decreasing pro-inflammatory cytokine production and expression of pro-inflammatory markers (Walker et al., J. Neuroinflammation 2012, 9:228; DePaul et al., Set Rep. 2015, 5:16795; Busch et al., J. Neurosci. 2011, 31(3): 944-953) and to induce the differentiation of M2 anti-inflammatory monocyte/macrophages, thereby promoting lung tissue repair by clearing pathogens and cellular debris while limiting inflammatory responses (Walker et al., J. Neuroinflammation 2012, 9:228; DePaul et al., Sci. Rep.
... keep reading on reddit โกDespite multiple clinical studies, no pharmacological treatments have proven effective for ARDS [1,2]. Recently, corticosteroids [3,4], and possibly IL6 receptor antagonists [5-7], have demonstrated favourable results in COVID-19 pneumonia [8]. However, a safe treatment that can reduce mortality of patients who develop ARDS, and improve quality of life for survivors, is still needed. Mesenchymal stromal cells (MSC) have demonstrated anti-inflammatory properties in animal models of ARDS [9-14]. Recently, several clinical studies have investigated MSC treatment for ARDS [15-19]. Multipotent adult progenitor cells are bone marrow-derived, GMP-manufactured, adherent, allogeneic stromal cells, with immunomodulatory properties similar to MSC. They have been well-tolerated in patients with stroke, myocardial infarction, and graft vs host disease [20-22]. Pre-clinical studies in a sheep model of ARDS demonstrated that multipotent adult progenitor cells improved blood oxygenation and carbon dioxide clearance, and reduced inflammation, pulmonary vascular pressures, and lung oedema [23,24]. We hypothesize that multipotent adult progenitor cells are safe in patients with ARDS, and through pleotropic effects, will shift host immune responses from pro-inflammatory towards anti-inflammatory, mitigating lung pathophysiology and promoting repair that could improve important clinical outcomes. The MUST-ARDS study, a multicentre, double-blind, randomised, placebo-controlled trial of multipotent adult progenitor cells in patients with moderate to severe ARDS, was presented at the 2019 American Thoracic Society International Conference [25].
https://www.repository.cam.ac.uk/handle/1810/330172
https://www.nature.com/articles/s41598-021-99540-1
This study was undertaken to plan the study design for Healios One-Bridge ARDS Trial in Japan.
Analysis in this study provided historical data to support a randomized, open-label multicenter phase II study evaluating the efficacy and safety of MultiStem cells [HLCM051], an allogeneic bone marrow-derived stem cell product, in patients with ARDS due to pneumonia (NCT03807804), that has been ongoing since February 2019.
Objectives: The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019). We systematically reviewed mortality in COVID-19 patients with ARDS and the potential role of systemic corticosteroids in COVID-19 patients.
Methods: Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle-Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS.
Results: The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23-56%). The pooled mortality estimate for China was 69% (95% CI: 67-72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58-86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2-29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%).
Conclusions: The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients.
Can COVI-MSC made a difference?
Overview of Stem Cell Therapy for Acute Respiratory Distress Syndrome with Focus on COVID 19
Objective: There are as yet no effective strategies to treat the novel COVID-19 and to stem its symptoms, including ARDS. This review examines recent research studies in humans to determine whether mesenchymal stem cells (MSCs) may be used effectively and safely to target potentially deadly lung damage that may follow infection.
Methods: A literature search was conducted to find published manuscripts on the treatment of ARDS and COVID-19 symptoms, disease presentation, and available treatment regimens. Electronic data bases of scientific articles and records of printed documents of JAMA journals were searched to find research publications on MSC
... keep reading on reddit โกAcute Respiratory Distress Syndrome (ARDS) HELP IS ON IT'S WAY
Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that allows fluid to leak into the lungs. Breathing becomes difficult and oxygen cannot get into the body. Most people who get ARDS are already at the hospital for trauma or illness. How Is ARDS Treated?
There is no cure for ARDS at this time. Treatment focuses on supporting the patient while the lungs heal. The goal of supportive care is getting enough oxygen into the blood and delivered to your body to prevent damage and removing the injury that caused ARDS to develop.
Ventilator support
All patients with ARDS will require extra oxygen. Oxygen alone is usually not enough, and high levels of oxygen can also injure the lung. A ventilator is a machine used to open airspaces that have shut down and help with the work of breathing. The ventilator is connected to the patient through a mask on the face or a tube inserted into the windpipe.
Prone positioning
ARDS patients are typically in bed on their back. When oxygen and ventilator therapies are at high levels and blood oxygen is still low, ARDS patients are sometimes turned over on their stomach to get more oxygen into the blood. This is called proning and may help improve oxygen levels in the blood for a while. It is a complicated task and some patients are too sick for this treatment.
Sedation and medications to prevent movement
To relieve shortness of breath and prevent agitation, the ARDS patient usually needs sedation. Sometimes added medications called paralytics are needed up front to help the patient adjust to the ventilator. These medications have significant side effects and their risks and benefits must be continuously monitored.
Fluid management
Doctors may give ARDS patients a medication called a diuretic to increase urination in hopes of removing excess fluid from the body to help prevent fluid from building up in the lungs. This must be done carefully, because too much fluid removal can lower blood pressure and lead to kidney problems.
Extracorporeal membrane oxygenation (ECMO)
ECMO is a very complicated treatment that takes blood outside of your body and pumps it through a membrane that adds oxygen, removes carbon dioxide and then returns the blood to your body. This is a high-risk therapy with many potential complications. It is not suitable for every ARDS patient.
Recovering from ARDS
ARDS patients may require
NEWS
Helios Co., Ltd. uses the somatic stem cell regenerative drug HLCM051 in Japan to target clinical trials (clinical trial name: TREASURE trial) and acute respiratory distress syndrome (ARDS) in the acute phase of cerebral infarction. The clinical trial (clinical trial name: ONE-BRIDGE trial. Patient enrollment completed in March 2021) is being conducted.
The HLCM051 used in these clinical trials is a stem cell product MultiStem developed by American bio-venture company Athersys, Inc. (hereinafter referred to as Asasis), which was signed by Helios and Asasis during the acute phase of cerebral infarction. It was introduced based on an exclusive license agreement for the development and sale of regenerative medicine products for ARDS in Japan.
Research on the mechanism of action of inflammatory response regulation of pluripotent adult progenitor cells (MAPCยฎ), which is a constituent cell of MultiStem, from Assasis has been peer-reviewed internationally in all areas of natural science and clinical science. Announced that it was published in the journal Scientific Reports.
The data reported this time is research on the potential mechanism by which MAPC promotes the differentiation and proliferation of regulatory T cells (Tregs) and affects immunosuppression.ย Tregs are important cells of the immune system that control tissue remodeling after inflammation and injury by multiple mechanisms.
In acutely ill patients with stroke, ARDS, etc., abnormally enhanced inflammatory response is known to lead to tissue and organ damage, and MultiStem is endogenous, including Treg differentiation, proliferation, and phenotypic activation. By strengthening the immune regulation mechanism, it suggests that it may reduce organ damage caused by inflammation and promote recovery after tissue damage.
Acute Respiratory Distress Syndrome (ARDS)
ARDS is not a single disease, but the immune system such as neutrophils is excessively induced by the underlying disease or trauma, and the lungs are injured by inflammation, resulting in pulmonary edema, resulting in severe respiratory distress. It is a general term for symptoms that cause failure.
According to the ARDS clinical practice guidelines, the mortality rate is 30-58%, which is a very poor prognosis.ย As a treatment for ARDS, systemic management centered on respiratory management using a respirator is performed in the intensive care unit.
https://pulse-beat.com/articles/APGU3
Summary of the article's main point: survivors of COVID-19 associated ARDS had poor exercise capacity, health status, and lower HRQoL scores after 8 months compared with the general population. More than 90% presented with mental health disorders, including PTSD, depression, and anxiety.
Highlights
โข
Most COVID-19 associated ARDS survivors have persistent symptoms beyond 8 months.
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At 8 months, COVID survivors with ARDS often have decreased exercise capacity.
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Almost all COVID survivors with ARDS develop at least one mental disorder.
โข
The HRQoL scores of most severe COVID-19 were worse than in the general population.
โข
Female sex, non-Caucasian race, and Charlson>2 were risk factors for a worse MCS score on the SF-36.
โข
Female sex and COPD were independent risk factors for a worse PCS score on the SF-36.
Abstract
Objectives
To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis.
Methods
All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6-minute walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied.
Results
Of 1,295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score.
Conclusion
COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.
https://doi.org/10.1016/j.jinf.2021.08.018
