The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within...The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.展开更多
The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens milli...The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.展开更多
Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has led to a significant number of mortalities worldwide.COVID-19 poses a serious threat to human l...Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has led to a significant number of mortalities worldwide.COVID-19 poses a serious threat to human life.The clinical manifestations of COVID-19 are diverse and severe and 20%of infected patients are reported to be in a critical condition.A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease.The lung function is affected,even after recovery,thereby greatly affecting the psychology and well-being of patients,and significantly reducing their quality of life.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known t...BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known that COVID-19 patients may have increased serum lactate dehydrogenase(LDH)levels in the early stage.The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients.AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis.METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25,2020 and divided them into survivors and nonsurvivors.The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria:Respiratory failure and required mechanical ventilation,the occurrence of shock,and the combined failure of other organs that required intensive care unit monitoring and treatments,according to the diagnostic criteria of critical COVID-19.Clinical data including symptoms,detection of SARS-CoV-2,chest computed tomography(CT)images,changes in serum LDH in different clinical phases,and prognosis were collected.Statistical analysis of the data was performed.Continuous variables were expressed as median(interquartile range)and compared with the Mann-Whitney U test.Categorical variables were compared with the Chi-square test.Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests.RESULTS According to chest CT images,we observed the alveolitis and fibrosis stages in all critical patients in this study.Most non-survivors died in the fibrosis stage.Nonsurvivors had fewer days of hospitalization,shorter disease duration,shorter duration of alveolitis and fibrosis,and had dyspnea symptoms at disease onset(P=0.05).Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors(449.0 U/L vs 288.0 U/L,P=0.0243;445.0 U/L vs 288.0 U/L,P=0.0199,respectively),while the first,lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase(449.0 U/L vs 225.5 U/L,P=0.0028;432.0 U/L vs 191.0 U/L,P=0.0007;1303.0 U/L vs 263.5 U/L,P=0.0001,respectively).The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L,respectively.In the fibrosis stage,non-survivors had more days with high LDH than survivors(7.0 d vs 0.0 d,P=0.0002).Importantly,patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase(22.0 d vs 36.5 d,P=0.0002),while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase(27.5 d vs 40.0 d,P=0.0008).The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage(100%vs 35.7%,P=0.0220).CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19.The rapid progressive fibrosis stage was more perilous than the alveolitis stage,even if SARS-CoV-2 is undetectable.展开更多
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently use...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently usedtreatment guideline is to manage the common symptoms like fever and cough,but doesn’t target the virus itself or halts serious complications arising from thisviral infection. Currently, SARS-CoV-2 exhibits many genetic modulations whichhave been associated with the appearance of highly contagious strains. Thenumber of critical cases of COVID-19 increases markedly, and many of theinfected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has beenextensively studied and confirmed. The impressive immunomodulation and antiinflammatoryactivity of MSCs have been recognized as a golden opportunity forthe treatment of COVID-19 and its associated complications. Moreover, MSCsregenerative and repairing abilities have been corroborated by many studies withpositive outcomes and high recovery rates. Based on that, MSCs infusion could bean effective mechanism in managing and stemming the serious complications andmultiple organ failure associated with COVID-19. In the present review, wediscuss the commonly reported complications of COVID-19 viral infection and theestablished and anticipated role of MSCs in managing these complications.展开更多
基金Supported by the Project of Special Funds for Science and Technology Cooperation in Guizhou Provinces and Zunyi City,No.Shengshikehe(2015)53.
文摘The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.
基金Supported by Shandong Provincial Natural Science Foundation,No.ZR2020QC097China Postdoctoral Science Foundation,No.2019M661033+7 种基金Jiangxi Key New Product Incubation Program Funded by Technical Innovation Guidance Program of Shangrao city,No.2020G002Tianjin Science and Technology Project for Overseas Students,No.JH-20180070802Natural Science Foundation of Tianjin,No.19JCQNJC12500Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2018PT31048Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences,No.2019PT310013National Science and Technology Major Projects of China for“Major New Drugs Innovation and Development”,No.2014ZX09508002-003National Natural Science Foundation of China,No.81330015and Science and Technology Project of Tianjin,No.17ZXSCSY00030.
文摘The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health.Two current studies have indicated a favorable role for mesenchymal stem/stromal cells(MSCs)in clinical remission of COVID-19 associated pulmonary diseases,yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction.In the present review,we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury,acute respiratory distress syndrome,and pulmonary fibrosis.Furthermore,we review the underlying mechanism of MSCs including direct-and trans-differentiation,autocrine and paracrine anti-inflammatory effects,homing,and neovascularization,as well as constitutive microenvironment.Finally,we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice.Collectively,this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.
文摘Background:The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has led to a significant number of mortalities worldwide.COVID-19 poses a serious threat to human life.The clinical manifestations of COVID-19 are diverse and severe and 20%of infected patients are reported to be in a critical condition.A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease.The lung function is affected,even after recovery,thereby greatly affecting the psychology and well-being of patients,and significantly reducing their quality of life.
基金Supported by National Natural Science Foundation of China,No.81800070Development Fund Program of Fujian Provincial Health and Family Planning Commission,China,No.2017-1-43.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak in China,constitutes a Public Health Emergency of International Concern.It is well known that COVID-19 patients may have increased serum lactate dehydrogenase(LDH)levels in the early stage.The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients.AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis.METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25,2020 and divided them into survivors and nonsurvivors.The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria:Respiratory failure and required mechanical ventilation,the occurrence of shock,and the combined failure of other organs that required intensive care unit monitoring and treatments,according to the diagnostic criteria of critical COVID-19.Clinical data including symptoms,detection of SARS-CoV-2,chest computed tomography(CT)images,changes in serum LDH in different clinical phases,and prognosis were collected.Statistical analysis of the data was performed.Continuous variables were expressed as median(interquartile range)and compared with the Mann-Whitney U test.Categorical variables were compared with the Chi-square test.Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests.RESULTS According to chest CT images,we observed the alveolitis and fibrosis stages in all critical patients in this study.Most non-survivors died in the fibrosis stage.Nonsurvivors had fewer days of hospitalization,shorter disease duration,shorter duration of alveolitis and fibrosis,and had dyspnea symptoms at disease onset(P=0.05).Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors(449.0 U/L vs 288.0 U/L,P=0.0243;445.0 U/L vs 288.0 U/L,P=0.0199,respectively),while the first,lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase(449.0 U/L vs 225.5 U/L,P=0.0028;432.0 U/L vs 191.0 U/L,P=0.0007;1303.0 U/L vs 263.5 U/L,P=0.0001,respectively).The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L,respectively.In the fibrosis stage,non-survivors had more days with high LDH than survivors(7.0 d vs 0.0 d,P=0.0002).Importantly,patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase(22.0 d vs 36.5 d,P=0.0002),while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase(27.5 d vs 40.0 d,P=0.0008).The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage(100%vs 35.7%,P=0.0220).CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19.The rapid progressive fibrosis stage was more perilous than the alveolitis stage,even if SARS-CoV-2 is undetectable.
文摘The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) orcoronavirus disease 2019 (COVID-19) pandemic has exhausted the health systemsin many countries with thousands cases diagnosed daily. The currently usedtreatment guideline is to manage the common symptoms like fever and cough,but doesn’t target the virus itself or halts serious complications arising from thisviral infection. Currently, SARS-CoV-2 exhibits many genetic modulations whichhave been associated with the appearance of highly contagious strains. Thenumber of critical cases of COVID-19 increases markedly, and many of theinfected people die as a result of respiratory failure and multiple organ dysfunction. The regenerative potential of mesenchymal stem cells (MSCs) has beenextensively studied and confirmed. The impressive immunomodulation and antiinflammatoryactivity of MSCs have been recognized as a golden opportunity forthe treatment of COVID-19 and its associated complications. Moreover, MSCsregenerative and repairing abilities have been corroborated by many studies withpositive outcomes and high recovery rates. Based on that, MSCs infusion could bean effective mechanism in managing and stemming the serious complications andmultiple organ failure associated with COVID-19. In the present review, wediscuss the commonly reported complications of COVID-19 viral infection and theestablished and anticipated role of MSCs in managing these complications.
