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1.
Int J Mol Sci ; 23(15)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1957348

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Acute Lung Injury/etiology , Acute Lung Injury/therapy , Animals , COVID-19/therapy , Immunomodulation , Mesenchymal Stem Cell Transplantation/methods , Models, Animal , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2
2.
Front Immunol ; 13: 871828, 2022.
Article in English | MEDLINE | ID: covidwho-1855360

ABSTRACT

Background and Objectives: The novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS). Methods: On Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed. Results: None of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray's lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1ß, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy. Conclusion: pc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.


Subject(s)
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Acute Lung Injury/etiology , Acute Lung Injury/therapy , COVID-19/therapy , Critical Illness , Humans , Pandemics , Respiratory Distress Syndrome/therapy
3.
Int J Mol Sci ; 23(7)2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1753510

ABSTRACT

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common clinical problem, leading to significant morbidity and mortality, and no effective pharmacotherapy exists. The problem of ARDS causing mortality became more apparent during the COVID-19 pandemic. Biotherapeutic products containing multipotent mesenchymal stromal cell (MMSC) secretome may provide a new therapeutic paradigm for human healthcare due to their immunomodulating and regenerative abilities. The content and regenerative capacity of the secretome depends on cell origin and type of cultivation (two- or three-dimensional (2D/3D)). In this study, we investigated the proteomic profile of the secretome from 2D- and 3D-cultured placental MMSC and lung fibroblasts (LFBs) and the effect of inhalation of freeze-dried secretome on survival, lung inflammation, lung tissue regeneration, fibrin deposition in a lethal ALI model in mice. We found that three inhaled administrations of freeze-dried secretome from 2D- and 3D-cultured placental MMSC and LFB protected mice from death, restored the histological structure of damaged lungs, and decreased fibrin deposition. At the same time, 3D MMSC secretome exhibited a more pronounced trend in lung recovery than 2D MMSC and LFB-derived secretome in some measures. Taking together, these studies show that inhalation of cell secretome may also be considered as a potential therapy for the management of ARDS in patients suffering from severe pneumonia, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, their effectiveness requires further investigation.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Pneumonia , Respiratory Distress Syndrome , Acute Lung Injury/therapy , Animals , COVID-19/therapy , Cell Culture Techniques , Female , Fibrin , Humans , Mesenchymal Stem Cell Transplantation/methods , Mice , Pandemics , Placenta , Pregnancy , Proteomics , Respiratory Distress Syndrome/therapy , SARS-CoV-2
4.
J Control Release ; 345: 214-230, 2022 05.
Article in English | MEDLINE | ID: covidwho-1747828

ABSTRACT

Mesenchymal stem cell-derived small extracellular vesicles (MSC-EVs) are promising nanotherapeutic agent for pneumonia (bacterial origin, COVID-19), but the optimal administration route and potential mechanisms of action remain poorly understood. This study compared the administration of MSC-EVs via inhalation and tail vein injection for the treatment of acute lung injury (ALI) and determined the host-derived mechanisms that may contribute to the therapeutic effects of MSC-EVs in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (macrophage cell line) and animal models. Luminex liquid chip and hematoxylin and eosin (HE) staining revealed that, compared with the vehicle control, inhaled MSC-EVs outperformed those injected via the tail vein, by reducing the expression of pro-inflammatory cytokines, increasing the expression of anti-inflammatory cytokine, and decreasing pathological scores in ALI. MSC-EV administration promoted the polarization of macrophages towards a M2 phenotype in vitro and in vivo (via inhalation). RNA sequencing revealed that immune and redox mediators, including TLR4, Arg1, and HO-1, were associated with the activity MSC-EVs against ALI mice. Western blotting and immunofluorescence revealed that correlative inflammatory and oxidative mediators were involved in the therapeutic effects of MSC-EVs in LPS-stimulated cells and mice. Moreover, variable expression of Nrf2 was observed following treatment with MSC-EVs in cell and animal models, and knockdown of Nrf2 attenuated the anti-inflammatory and antioxidant activities of MSC-EVs in LPS-stimulated macrophages. Together, these data suggest that inhalation of MSC-EVs as a noninvasive strategy for attenuation of ALI, and the adaptive regulation of Nrf2 may contribute to their anti-inflammatory and anti-oxidant activity in mice.


Subject(s)
Acute Lung Injury , COVID-19 , Extracellular Vesicles , Mesenchymal Stem Cells , Acute Lung Injury/therapy , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/therapeutic use , Antioxidants , Cytokines/metabolism , Disease Models, Animal , Extracellular Vesicles/metabolism , Lipopolysaccharides , Mesenchymal Stem Cells/metabolism , Mice , NF-E2-Related Factor 2/metabolism
5.
Bull Exp Biol Med ; 172(4): 423-429, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1696762

ABSTRACT

We studied the lung-protective effect and mechanisms of the anti-inflammatory and antioxidant effects of ultra-short-wave diathermy (USWD) in a rat model of LPS-induced acute lung injury. Histological examination of the lung tissues was performed and the levels of oxidative stress-related factors and inflammatory cytokines were measured. It was shown that the lung injury score, the lung wet-to-dry weight ratio (W/D), oxidative stress-related factors malondialdehyde and acyl-CoA synthetase long-chain family member 4 (ACSL4), and inflammatory cytokines were increased after LPS administration, while USWD treatment reduced these parameters. In addition, superoxide dismutase and glutathione peroxidase 4 were decreased in rats with LPS-induced acute lung injury, while USWD therapy up-regulated the expression of these enzymes. Thus, USWD could antagonize lung injury by inhibiting oxidative stress and inflammatory response in rats with acute lung injury. USWD can be a promising adjunctive treatment to counter oxidative stress and inflammation and a potential therapeutic candidate for the treatment of patients with this pathology.


Subject(s)
Acute Lung Injury , Diathermy , Acute Lung Injury/drug therapy , Acute Lung Injury/therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/metabolism , Humans , Lipopolysaccharides/pharmacology , Lung , Oxidative Stress , Radio Waves , Rats
6.
Stem Cell Res Ther ; 13(1): 20, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1638634

ABSTRACT

BACKGROUND: Although 90% of infections with the novel coronavirus 2 (COVID-19) are mild, many patients progress to acute respiratory distress syndrome (ARDS) which carries a high risk of mortality. Given that this dysregulated immune response plays a key role in the pathology of COVID-19, several clinical trials are underway to evaluate the effect of immunomodulatory cell therapy on disease progression. However, little is known about the effect of ARDS associated pro-inflammatory mediators on transplanted stem cell function and survival, and any deleterious effects could undermine therapeutic efficacy. As such, we assessed the impact of inflammatory cytokines on the viability, and paracrine profile (extracellular vesicles) of bone marrow-derived mesenchymal stromal cells, heart-derived cells, and umbilical cord-derived mesenchymal stromal cells. METHODS: All cell products were manufactured and characterized to established clinical release standards by an accredited clinical cell manufacturing facility. Cytokines and Extracellular vesicles in the cell conditioned media were profiled using proteomic array and nanoparticle tracking analysis. Using a survey of the clinical literature, 6 cytotoxic cytokines implicated in the progression of COVID-19 ARDS. Flow cytometry was employed to determine receptor expression of these 6 cytokines in three cell products. Based on clinical survey and flow cytometry data, a cytokine cocktail that mimics cytokine storm seen in COVID-19 ARDS patients was designed and the impact on cytokine cocktail on viability and paracrine secretory ability of cell products were assessed using cell viability and nanoparticle tracking analysis. RESULTS: Flow cytometry revealed the presence of receptors for all cytokines but IL-6, which was subsequently excluded from further experimentation. Despite this widespread expression, exposure of each cell type to individual cytokines at doses tenfold greater than observed clinically or in combination at doses associated with severe ARDS did not alter cell viability or extracellular vesicle character/production in any of the 3 cell products. CONCLUSIONS: The paracrine production and viability of the three leading cell products under clinical evaluation for the treatment of severe COVID-19 ARDS are not altered by inflammatory mediators implicated in disease progression.


Subject(s)
Acute Lung Injury , COVID-19 , Mesenchymal Stem Cell Transplantation , Acute Lung Injury/therapy , Cytokines , Humans , Proteomics , SARS-CoV-2
7.
Int J Mol Sci ; 22(15)2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1335093

ABSTRACT

Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/trends , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/therapy , Acute Lung Injury/complications , Acute Lung Injury/therapy , COVID-19/complications , COVID-19/therapy , Exosomes/transplantation , Humans , Mesenchymal Stem Cells/chemistry , Respiratory Distress Syndrome/etiology
8.
Br J Anaesth ; 127(3): 353-364, 2021 09.
Article in English | MEDLINE | ID: covidwho-1293599

ABSTRACT

COVID-19 pneumonia is associated with hypoxaemic respiratory failure, ranging from mild to severe. Because of the worldwide shortage of ICU beds, a relatively high number of patients with respiratory failure are receiving prolonged noninvasive respiratory support, even when their clinical status would have required invasive mechanical ventilation. There are few experimental and clinical data reporting that vigorous breathing effort during spontaneous ventilation can worsen lung injury and cause a phenomenon that has been termed patient self-inflicted lung injury (P-SILI). The aim of this narrative review is to provide an overview of P-SILI pathophysiology and the role of noninvasive respiratory support in COVID-19 pneumonia. Respiratory mechanics, vascular compromise, viscoelastic properties, lung inhomogeneity, work of breathing, and oesophageal pressure swings are discussed. The concept of P-SILI has been widely investigated in recent years, but controversies persist regarding its mechanisms. To minimise the risk of P-SILI, intensivists should better understand its underlying pathophysiology to optimise the type of noninvasive respiratory support provided to patients with COVID-19 pneumonia, and decide on the optimal timing of intubation for these patients.


Subject(s)
Acute Lung Injury/epidemiology , Acute Lung Injury/therapy , Anesthesiologists , COVID-19 , Noninvasive Ventilation , Respiration, Artificial , Ventilator-Induced Lung Injury/epidemiology , Ventilator-Induced Lung Injury/therapy , Humans , Noninvasive Ventilation/adverse effects , Positive-Pressure Respiration/adverse effects , Respiratory Insufficiency , Respiratory Mechanics
9.
Front Immunol ; 11: 604944, 2020.
Article in English | MEDLINE | ID: covidwho-1058416

ABSTRACT

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.


Subject(s)
Adenosine/metabolism , Hypoxia/metabolism , Inflammation/metabolism , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/therapy , Disease Management , Disease Susceptibility , Humans , Hypoxia-Inducible Factor 1/metabolism , Inflammation/etiology , Molecular Targeted Therapy , Receptors, Purinergic P1/metabolism , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/therapy , Signal Transduction
11.
Stem Cell Res Ther ; 11(1): 437, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-864994

ABSTRACT

The COVID-19 pandemic has negatively impacted the global public health and the international economy; therefore, there is an urgent need for an effective therapy to treat COVID-19 patients. Mesenchymal stem cells (MSCs) have been proposed as an emerging therapeutic option for the SARS-CoV-2 infection. Recently, numerous clinical trials have been registered to examine the safety and efficacy of different types of MSCs and their exosomes for treating COVID-19 patients, with less published data on the mechanism of action. Although there is no approved effective therapy for COVID-19 as of yet, MSC therapies showed an improvement in the treatment of some COVID-19 patients. MSC's therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear. The use of poorly characterized MSC products remains one of the most significant drawbacks of MSC-based therapy, which could theoretically promote the risk for thromboembolism. Optimizing the clinical-grade production of MSCs and establishing a consensus on registered clinical trials based on cell-product characterization and mode of delivery would aid in laying the foundation for a safe and effective therapy in COVID-19. In this review, we shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. We further highlight the challenges and opportunities in the use of MSC-based therapy.


Subject(s)
Acute Lung Injury/therapy , Coronavirus Infections/therapy , Cytokine Release Syndrome/therapy , Exosomes/transplantation , Mesenchymal Stem Cell Transplantation/methods , Pneumonia, Viral/therapy , Acute Lung Injury/virology , Betacoronavirus , COVID-19 , Cell- and Tissue-Based Therapy/methods , Humans , Mesenchymal Stem Cells/metabolism , Pandemics , SARS-CoV-2
12.
F1000Res ; 9: 769, 2020.
Article in English | MEDLINE | ID: covidwho-799084

ABSTRACT

Background: Numerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. Methods: Nineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. Results: Compared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO 2/FiO 2) ratio. The oxygen extraction index changes mirrored those of the PaO 2/FiO 2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. Conclusions: These novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.


Subject(s)
Acute Lung Injury/physiopathology , Acute Lung Injury/therapy , Extracorporeal Membrane Oxygenation , Smoke/adverse effects , Animals , Coronary Circulation , Female , Oxygen/blood , Partial Pressure , Sheep
13.
Front Immunol ; 11: 1626, 2020.
Article in English | MEDLINE | ID: covidwho-646832

ABSTRACT

Most SARS-CoV2 infections will not develop into severe COVID-19. However, in some patients, lung infection leads to the activation of alveolar macrophages and lung epithelial cells that will release proinflammatory cytokines. IL-6, TNF, and IL-1ß increase expression of cell adhesion molecules (CAMs) and VEGF, thereby increasing permeability of the lung endothelium and reducing barrier protection, allowing viral dissemination and infiltration of neutrophils and inflammatory monocytes. In the blood, these cytokines will stimulate the bone marrow to produce and release immature granulocytes, that return to the lung and further increase inflammation, leading to acute respiratory distress syndrome (ARDS). This lung-systemic loop leads to cytokine storm syndrome (CSS). Concurrently, the acute phase response increases the production of platelets, fibrinogen and other pro-thrombotic factors. Systemic decrease in ACE2 function impacts the Renin-Angiotensin-Kallikrein-Kinin systems (RAS-KKS) increasing clotting. The combination of acute lung injury with RAS-KKS unbalance is herein called COVID-19 Associated Lung Injury (CALI). This conservative two-hit model of systemic inflammation due to the lung injury allows new intervention windows and is more consistent with the current knowledge.


Subject(s)
Acute Lung Injury/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Lung/immunology , Pneumonia, Viral/immunology , Severe Acute Respiratory Syndrome/immunology , Systemic Inflammatory Response Syndrome/immunology , Acute Lung Injury/pathology , Acute Lung Injury/therapy , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Humans , Lung/pathology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/therapy , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy
14.
Stem Cell Res Ther ; 11(1): 192, 2020 05 24.
Article in English | MEDLINE | ID: covidwho-343284

ABSTRACT

Acute lung injury (ALI), an increasingly devastating human disorder, is characterized by a multitude of lung changes arising from a wide variety of lung injuries. Viral infection is the main cause of morbidity and mortality in ALI and acute respiratory distress syndrome (ARDS) patients. In particular, influenza virus, coronavirus, and other respiratory viruses circulate in nature in various animal species and can cause severe and rapidly spread human infections. Although scientific advancements have allowed for rapid progress to be made to understand the pathogenesis and develop therapeutics after each viral pandemic, few effective methods to treat virus-induced ALI have been described. Recently, stem cell therapy has been widely used in the treatment of various diseases, including ALI. In this review, we detail the present stem cell-based therapeutics for lung injury caused by influenza virus and the outlook for the future state of stem cell therapy to deal with emerging influenza and coronaviruses.


Subject(s)
Acute Lung Injury/therapy , Coronavirus/pathogenicity , Orthomyxoviridae/pathogenicity , Stem Cell Transplantation , Acute Lung Injury/etiology , Acute Lung Injury/virology , Betacoronavirus/pathogenicity , Cell- and Tissue-Based Therapy , Cytokines/metabolism , Humans , Mesenchymal Stem Cells/cytology , SARS-CoV-2
15.
Crit Care ; 24(1): 198, 2020 05 06.
Article in English | MEDLINE | ID: covidwho-186729

ABSTRACT

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8-12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality.


Subject(s)
Acute Lung Injury/diagnostic imaging , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/therapy , Acute Lung Injury/epidemiology , Acute Lung Injury/therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Creatine Kinase/blood , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Radiography , Respiration, Artificial , Respiratory Distress Syndrome/classification , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2 , Severity of Illness Index , Time Factors
16.
Stem Cell Res Ther ; 11(1): 169, 2020 05 04.
Article in English | MEDLINE | ID: covidwho-165146

ABSTRACT

The outbreak of 2019 novel coronavirus disease (COVID-19) worldwide is becoming rapidly a major concern. The number of severe cases has increased dramatically worldwide, while specific treatment options are scarce. The main pathologic features of severe or critical COVID-19 were consistent with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS), characterized by cellular fibromyxoid exudates, extensive pulmonary inflammation, pulmonary edema, and hyaline membrane formation. Mesenchymal stem cells (MSCs) can balance the inflammatory response and has been mentioned to be effective on ALI/ARDS from both infectious and noninfectious causes previously, presenting an important opportunity to be applied to COVID-19. In this commentary, we summarize the clinical trials of MSCs treatments on ALI/ARDS and raise MSCs as a hopefully alternative therapy for severe or critical COVID-19.


Subject(s)
Coronavirus Infections/therapy , Mesenchymal Stem Cell Transplantation , Pneumonia, Viral/therapy , Acute Lung Injury/therapy , Animals , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/therapy
17.
Eur Respir J ; 55(5)2020 05.
Article in English | MEDLINE | ID: covidwho-143997

ABSTRACT

Patients with COVID-19 present a broad spectrum of clinical presentation. Whereas hypoxaemia is the marker of severity, different strategies of management should be customised to five specific individual phenotypes. Many intubated patients present with phenotype 4, characterised by pulmonary hypoxic vasoconstriction, being associated with severe hypoxaemia with "normal" (>40 mL·cmH2O-1) lung compliance and likely representing pulmonary microvascular thrombosis. Phenotype 5 is often associated with high plasma procalcitonin and has low pulmonary compliance, Which is a result of co-infection or acute lung injury after noninvasive ventilation. Identifying these clinical phenotypes and applying a personalised approach would benefit the optimisation of therapies and improve outcomes.


Subject(s)
Acute Lung Injury/physiopathology , Betacoronavirus/genetics , Coronavirus Infections/genetics , Phenotype , Pneumonia, Viral/genetics , /genetics , Acute Lung Injury/therapy , Acute Lung Injury/virology , Biomarkers/blood , Biomedical Research , COVID-19 , Coronavirus Infections/therapy , Disease Management , Female , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Lung Compliance/genetics , Male , Pandemics , Pneumonia, Viral/therapy , Procalcitonin/metabolism , SARS-CoV-2
18.
Indian J Pediatr ; 87(6): 433-442, 2020 06.
Article in English | MEDLINE | ID: covidwho-125227

ABSTRACT

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health crisis threatening humanity at this point in time. Transmission of the infection occurs by inhalation of infected droplets or direct contact with soiled surfaces and fomites. It should be suspected in all symptomatic children who have undertaken international travel in the last 14 d, all hospitalized children with severe acute respiratory illness, and asymptomatic direct and high-risk contacts of a confirmed case. Clinical symptoms are similar to any acute respiratory viral infection with less pronounced nasal symptoms. Disease seems to be milder in children, but situation appears to be changing. Infants and young children had relatively more severe illness than older children. The case fatality rate is low in children. Diagnosis can be confirmed by Reverse transcriptase - Polymerase chain reaction (RT-PCR) on respiratory specimen (commonly nasopharyngeal and oropharyngeal swab). Rapid progress is being made to develop rapid diagnostic tests, which will help ramp up the capacity to test and also reduce the time to getting test results. Management is mainly supportive care. In severe pneumonia and critically ill children, trial of hydroxychloroquine or lopinavir/ritonavir should be considered. As per current policy, children with mild disease also need to be hospitalized; if this is not feasible, these children may be managed on ambulatory basis with strict home isolation. Pneumonia, severe disease and critical illness require admission and aggressive management for acute lung injury and shock and/or multiorgan dysfunction, if present. An early intubation is preferred over non-invasive ventilation or heated, humidified, high flow nasal cannula oxygen, as these may generate aerosols increasing the risk of infection in health care personnel. To prevent post discharge dissemination of infection, home isolation for 1-2 wk may be advised. As of now, no vaccine or specific chemotherapeutic agents are approved for children.


Subject(s)
Acute Lung Injury/etiology , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Palliative Care , Pneumonia, Viral/therapy , Acute Lung Injury/therapy , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/virology , Disease Outbreaks/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Infant , Lopinavir/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Protease Inhibitors/therapeutic use , Respiratory Distress Syndrome , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/therapeutic use , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/therapy
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