Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate...Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate.On the date this review was written,SARS-CoV-2 infected about 96 million people and killed about 2 million people.Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2(ACE2)receptor expression or cytokine storm strength production.In a similar pattern,hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming,which worsens the hepatic impairment and increases the mortality rate.In this review,the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed.Besides,we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.展开更多
Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used...Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.展开更多
patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury ma...patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.展开更多
Objective:To explore the possible mechanism of Qingfei Paibu Decoction in the treatment of COVID-19 from the perspective of cytokine storm by network pharmacology.Methods: The TCMSP and SymMap databases were used to s...Objective:To explore the possible mechanism of Qingfei Paibu Decoction in the treatment of COVID-19 from the perspective of cytokine storm by network pharmacology.Methods: The TCMSP and SymMap databases were used to screen out the active components and targets of Qingfei Paibu Decoction;The GeneCards database was used to screen the predicted targets of COVID-19;Two targets were mapped;The STRING database and Cytoscape3.7.2 software were used to construct the network diagram of active drag-ingredient-target and screen out the core components and targets;The GO enrichment analysis and KEGG pathway enrichment analysis were carried out by OmicShare cloud platform and David respectively.Results:A total of 52 potential targets of Qingfei Paibu Decoction for the treatment of COVID-19 were obtained, among which 17 were core targets related to inflammation, mainly including cytokines such as IL, IFN, TNF and chemokines. And 26 core components were obtained, including quercetin, luteolin, kaempferol, naringenin, and baicalein;The GO enrichment results showed 224 biological processes, 15 molecular functions and 33 cell components related to inflammation;There were 5 inflammatory signaling pathways in KEGG enrichment results, including TNF signaling pathway, Nod-like receptor signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway and cytokine receptor interaction. Conclusion: Qingfei Paibu Decoction can inhibit cytokine storms by acting on multiple targets and pathways with multiple components and thus treat COVID-19.展开更多
At present,COVID-19 is outbreaking worldwide,and the severity of the disease is closely related to the intensity of cytokine storm and inflammatory response.Cytokine storm is an excessive immune response to external s...At present,COVID-19 is outbreaking worldwide,and the severity of the disease is closely related to the intensity of cytokine storm and inflammatory response.Cytokine storm is an excessive immune response to external stimuli,with complex pathogenesis and high mortality.In the New Coronavirus Infected Pneumonia Diagnosis and Treatment Program,a variety of measures are recommended for treatment,such as respiratory support,circulatory support,glucocorticoids and traditional Chinese medicine prescriptions to suppress the cytokine storm in the late clinical stage.At present,the combination of traditional Chinese medicine and Western medicine has achieved good results in clinical practice.Traditional Chinese medicine has contributed greatly to human health and world civilization,and is also a characteristic health resource in China.It has been adhering to the principle of"treating the symptoms at the time and treating the root cause in ordinary time",and has shown obvious efficacy in a variety of immune diseases.Ocean occupies 70%of the earth's surface,which contains abundant resources of traditional Chinese medicine.This paper analyzed the effect of marine algae traditional Chinese medicine on cytokine storm and immune regulation,hoping to provide a supplement to the existing application of traditional Chinese medicine,and provide some references for the development of drugs to inhibit cytokine storm from the sea.展开更多
The recently emergent disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),transmitted by droplets and aerosols,was named coronavirus disease 2019(COVID-19)by World Health Organization.Pre...The recently emergent disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),transmitted by droplets and aerosols,was named coronavirus disease 2019(COVID-19)by World Health Organization.Predominantly,the disease progress is asymptomatic or mild,but one-fifth of the patients advance to severe or critical illness.In severe COVID-19 patients,type-2 T helper cells release numerous cytokines;this excessive immune response is named as cytokine storm.The cytokine storm,which is the hallmark of the COVID-19 induced by the disease and aggravates due to lack of proper immune response,similar to SARS and Middle East respiratory syndrome(MERS),and the disease status may progress forward to acute respiratory distress syndrome(ARDS),systemic inflammatory response syndrome,multi-organ dysfunction syndrome,and death.Mesenchymal stromal cell transplantation is up-and-coming in treating many diseases such as HIV,hepatitis B,influenza,coronavirus diseases(SARS,MERS),lung injuries,and ARDS.Upon closer inspection on respiratory diseases,COVID-19,influenza,SARS,and MERS have similarities in patho-genesis,especially cytokine and immune response profiles.These comparable features in terms of the cytokine storm will provide hints for the treatment of COVID-19.展开更多
Spreading COVID-19 disease caused by coronavirus 2 causes tremendous health challenges worldwide. Owing to a high transmission rate, fast-spreading disease, asymptomatic carriers, and high infectivity, we observe a pa...Spreading COVID-19 disease caused by coronavirus 2 causes tremendous health challenges worldwide. Owing to a high transmission rate, fast-spreading disease, asymptomatic carriers, and high infectivity, we observe a pandemic status that we follow today. Although there are different reports of case fatality rates around the globe, the primary determinant of mortality is age. Symptoms of COVID-19 disease vary from asymptomatic individuals to severe acute respiratory distress syndrome (ARDS) and death. The most common complication of COVID-19 is ARDS. Hyperinflammation due to excessive immune response to coronavirus is the leading cause of severe symptoms seen in the course of COVID-19. The virus enters cells utilizing the S1 subunit through the ACE2 receptor. The innate immune response is the primary immune reaction to virus entry. RNA viruses, including corona-virus, replicate in the cytoplasm, assemble, and then exit by exocytosis. Some suggest that SARS-Cov2 uses cell-cell fusion to infect adjacent cells. Different sensors detect the virus particles in the endosomal compartment and cytoplasm, and infected cells induce an immune response to surrounding cells. As a result, the production of cytokines and chemokines such as interferons (INFs) will be augmented. Since coronavirus uses different means to evade the immune system, it is difficult for immune cells to “sense” them;thus, the coronavirus response is not adequate. It has been showing that even a sufficient level of immunoglobulin response couldn’t neutralize virus replication. Therefore, the innate immune response is unable to eradicate SARS-Cov2, causes overexpression of cytokines and chemokines that cannot eliminate the virus. Diminished INFs secretion and apoptosis of regulatory T cells (Treg) are the leading cause of dysregulated immune response in a cytokine storm. Inflammatory cells attack infected and uninfected cells, causing more inflammation and apoptosis of endothelial and epithelial cells. In the end, organ failure occurs due to immune cells’ overactivity, cell proliferation, hemorrhage, microthrombi, and remodeling of tissue cells. This review discusses the immune response and pathomechanisms of the associated symptoms in COVID-19.展开更多
We examined SARS-CoV-2(Covid-19)available treatments and prophylactic methods that included interventions associated with inhibiting the“type II transmembrane serine protease”(TMPRSS2)to limit the fusion between the...We examined SARS-CoV-2(Covid-19)available treatments and prophylactic methods that included interventions associated with inhibiting the“type II transmembrane serine protease”(TMPRSS2)to limit the fusion between the Covid-19 Spike proteins and ACE2 receptors,or newly developed therapeutics like Remdesivir that interferes with the viral RNA replication.We explored the dilemma of ACE2 receptors that have a protective function against high blood pressure associated disorders,yet,they serve as the viral points of entry,elevating the probability of infection.Human tissues’analysis reveals a higher ACE2 expression in adipose tissue,placing obesity-related conditions in the eye of the pandemic storm.It primarily exposes males due to the surge of ACE2 receptors in the testes along with other tissues.Males manifest a relatively higher positive ACE2 correlations with certain immune cells in the lungs,thyroid,adrenals,liver and colon,while females evidence higher ACE2 correlations with immune cells in the heart.The remaining tissues’ACE2/immunity expressions are equivalent in both sexes,indicating that despite its preference for males,the threat of Covid-19 can easily target females.Recent reports indicate that Covid-19 is empowered by hindering the critical process of viral recognition during the adaptive immune response leading to the“cytokine storm”,the aggravated immune response that indiscriminately perseveres,rampaging the host’s vital organs.Sedentary lifestyle,age-related hormonal imbalance,and adiposity induced inflammation predispose the body to the immune collapse following Covid-19 invasion,spotlighting the detrimental aftermath of metabolic dysfunction,and excess food consumption provoked by elevated cortisol and dysregulated appetite hormones.ACE 2 expression is suppressed in the skeletal muscle,rendering fitness and weight management an effective Covid-19 preventive intervention,along with social distancing,hygiene,and facial coverings.Physical activity,or exercise alternative methods have recently demonstrated statistically significant reductions of the inflammatory marker C-Reactive Protein(CRP),triglycerides,visceral fat,cortisol and the orexigenic hormone ghrelin,juxtaposed by optimal increases of IGF-1,skeletal muscle mass,Free T3,HDL,and the anorexic hormone leptin.展开更多
During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Sev...During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.展开更多
Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,whi...Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.展开更多
An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,decipherin...An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the most recent global health threat,is spreading throughout the world with worrisome speed,and the current wave of coronavirus disease 2019(COVID-19)seems t...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the most recent global health threat,is spreading throughout the world with worrisome speed,and the current wave of coronavirus disease 2019(COVID-19)seems to have no mercy.While this mysterious virus challenges our ability to control viral infections,our opportunities to control the COVID-19 pandemic are gradually fading.Currently,pandemic management relies on preventive interventions.Although prevention is a good strategy to mitigate SARS-CoV-2 transmission,it still cannot be considered an absolute solution to eliminate this pandemic.Currently,developing a potent immunity against this viral infection seems to be the most promising strategy to drive down this ongoing global tragedy.However,with the emergence of new challenges in the context of immune responses to COVID-19,the road to control this devastating pandemic seems bumpier;thus,it is pivotal to characterize the dynamics of host immune responses to COVID-19,in order to develop efficient prophylactic and therapeutic tools.This begs the question of whether the effector mechanisms of the immune system are indeed potent or a possible contributing factor to developing more severe and lethal forms of COVID-19.In this review,the possible role of the immunopathologic phenomena including antibody-dependent enhancement,cytokine storm,and original antigenic sin in severity and mortality of COVID-19 will be discussed.展开更多
The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)was identified in December 2019,in Wuhan,China.The virus was rapidly spread worldwide,causing coronavirus disease 2019(COVID-19)pandemic.Al...The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)was identified in December 2019,in Wuhan,China.The virus was rapidly spread worldwide,causing coronavirus disease 2019(COVID-19)pandemic.Although COVID-19 is presented,usually,with typical respiratory symptoms(i.e.,dyspnea,cough)and fever,extrapulmonary manifestations are also encountered.Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and,even,acute liver failure.The pathogenesis of liver damage is not clearly defined;multiple mechanisms contribute to liver disorder,including direct cytopathic viral effect,cytokine storm and immune-mediated hepatitis,hypoxic injury,and druginduced liver toxicity.Patients with underlying chronic liver disease(i.e.,cirrhosis,non-alcoholic fatty liver disease,alcohol-related liver disease,hepatocellular carcinoma,etc.)may have greater risk to develop both severe COVID-19 and further liver deterioration,and,as a consequence,certain issues should be considered during disease management.The aim of this review is to present the prevalence,clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection.Moreover,we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.展开更多
文摘Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate.On the date this review was written,SARS-CoV-2 infected about 96 million people and killed about 2 million people.Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2(ACE2)receptor expression or cytokine storm strength production.In a similar pattern,hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming,which worsens the hepatic impairment and increases the mortality rate.In this review,the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed.Besides,we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.
文摘Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvanttherapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lunginjury and cytokine storm. Several published studies, which used MSCs toalleviate COVID-19-associated acute lung injury and cytokine storm, reportedpromising results. However, the evidence came from a case report, case series,and clinical trials with a limited number of participants. Therefore, more studiesare needed to get robust proof of MSC beneficial effects.
文摘patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.
基金The emergency project for COVID-19 prevention and control of Beijing university of Chinese medicine (2020-JYB-YJ-006)
文摘Objective:To explore the possible mechanism of Qingfei Paibu Decoction in the treatment of COVID-19 from the perspective of cytokine storm by network pharmacology.Methods: The TCMSP and SymMap databases were used to screen out the active components and targets of Qingfei Paibu Decoction;The GeneCards database was used to screen the predicted targets of COVID-19;Two targets were mapped;The STRING database and Cytoscape3.7.2 software were used to construct the network diagram of active drag-ingredient-target and screen out the core components and targets;The GO enrichment analysis and KEGG pathway enrichment analysis were carried out by OmicShare cloud platform and David respectively.Results:A total of 52 potential targets of Qingfei Paibu Decoction for the treatment of COVID-19 were obtained, among which 17 were core targets related to inflammation, mainly including cytokines such as IL, IFN, TNF and chemokines. And 26 core components were obtained, including quercetin, luteolin, kaempferol, naringenin, and baicalein;The GO enrichment results showed 224 biological processes, 15 molecular functions and 33 cell components related to inflammation;There were 5 inflammatory signaling pathways in KEGG enrichment results, including TNF signaling pathway, Nod-like receptor signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway and cytokine receptor interaction. Conclusion: Qingfei Paibu Decoction can inhibit cytokine storms by acting on multiple targets and pathways with multiple components and thus treat COVID-19.
文摘At present,COVID-19 is outbreaking worldwide,and the severity of the disease is closely related to the intensity of cytokine storm and inflammatory response.Cytokine storm is an excessive immune response to external stimuli,with complex pathogenesis and high mortality.In the New Coronavirus Infected Pneumonia Diagnosis and Treatment Program,a variety of measures are recommended for treatment,such as respiratory support,circulatory support,glucocorticoids and traditional Chinese medicine prescriptions to suppress the cytokine storm in the late clinical stage.At present,the combination of traditional Chinese medicine and Western medicine has achieved good results in clinical practice.Traditional Chinese medicine has contributed greatly to human health and world civilization,and is also a characteristic health resource in China.It has been adhering to the principle of"treating the symptoms at the time and treating the root cause in ordinary time",and has shown obvious efficacy in a variety of immune diseases.Ocean occupies 70%of the earth's surface,which contains abundant resources of traditional Chinese medicine.This paper analyzed the effect of marine algae traditional Chinese medicine on cytokine storm and immune regulation,hoping to provide a supplement to the existing application of traditional Chinese medicine,and provide some references for the development of drugs to inhibit cytokine storm from the sea.
文摘The recently emergent disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),transmitted by droplets and aerosols,was named coronavirus disease 2019(COVID-19)by World Health Organization.Predominantly,the disease progress is asymptomatic or mild,but one-fifth of the patients advance to severe or critical illness.In severe COVID-19 patients,type-2 T helper cells release numerous cytokines;this excessive immune response is named as cytokine storm.The cytokine storm,which is the hallmark of the COVID-19 induced by the disease and aggravates due to lack of proper immune response,similar to SARS and Middle East respiratory syndrome(MERS),and the disease status may progress forward to acute respiratory distress syndrome(ARDS),systemic inflammatory response syndrome,multi-organ dysfunction syndrome,and death.Mesenchymal stromal cell transplantation is up-and-coming in treating many diseases such as HIV,hepatitis B,influenza,coronavirus diseases(SARS,MERS),lung injuries,and ARDS.Upon closer inspection on respiratory diseases,COVID-19,influenza,SARS,and MERS have similarities in patho-genesis,especially cytokine and immune response profiles.These comparable features in terms of the cytokine storm will provide hints for the treatment of COVID-19.
文摘Spreading COVID-19 disease caused by coronavirus 2 causes tremendous health challenges worldwide. Owing to a high transmission rate, fast-spreading disease, asymptomatic carriers, and high infectivity, we observe a pandemic status that we follow today. Although there are different reports of case fatality rates around the globe, the primary determinant of mortality is age. Symptoms of COVID-19 disease vary from asymptomatic individuals to severe acute respiratory distress syndrome (ARDS) and death. The most common complication of COVID-19 is ARDS. Hyperinflammation due to excessive immune response to coronavirus is the leading cause of severe symptoms seen in the course of COVID-19. The virus enters cells utilizing the S1 subunit through the ACE2 receptor. The innate immune response is the primary immune reaction to virus entry. RNA viruses, including corona-virus, replicate in the cytoplasm, assemble, and then exit by exocytosis. Some suggest that SARS-Cov2 uses cell-cell fusion to infect adjacent cells. Different sensors detect the virus particles in the endosomal compartment and cytoplasm, and infected cells induce an immune response to surrounding cells. As a result, the production of cytokines and chemokines such as interferons (INFs) will be augmented. Since coronavirus uses different means to evade the immune system, it is difficult for immune cells to “sense” them;thus, the coronavirus response is not adequate. It has been showing that even a sufficient level of immunoglobulin response couldn’t neutralize virus replication. Therefore, the innate immune response is unable to eradicate SARS-Cov2, causes overexpression of cytokines and chemokines that cannot eliminate the virus. Diminished INFs secretion and apoptosis of regulatory T cells (Treg) are the leading cause of dysregulated immune response in a cytokine storm. Inflammatory cells attack infected and uninfected cells, causing more inflammation and apoptosis of endothelial and epithelial cells. In the end, organ failure occurs due to immune cells’ overactivity, cell proliferation, hemorrhage, microthrombi, and remodeling of tissue cells. This review discusses the immune response and pathomechanisms of the associated symptoms in COVID-19.
文摘We examined SARS-CoV-2(Covid-19)available treatments and prophylactic methods that included interventions associated with inhibiting the“type II transmembrane serine protease”(TMPRSS2)to limit the fusion between the Covid-19 Spike proteins and ACE2 receptors,or newly developed therapeutics like Remdesivir that interferes with the viral RNA replication.We explored the dilemma of ACE2 receptors that have a protective function against high blood pressure associated disorders,yet,they serve as the viral points of entry,elevating the probability of infection.Human tissues’analysis reveals a higher ACE2 expression in adipose tissue,placing obesity-related conditions in the eye of the pandemic storm.It primarily exposes males due to the surge of ACE2 receptors in the testes along with other tissues.Males manifest a relatively higher positive ACE2 correlations with certain immune cells in the lungs,thyroid,adrenals,liver and colon,while females evidence higher ACE2 correlations with immune cells in the heart.The remaining tissues’ACE2/immunity expressions are equivalent in both sexes,indicating that despite its preference for males,the threat of Covid-19 can easily target females.Recent reports indicate that Covid-19 is empowered by hindering the critical process of viral recognition during the adaptive immune response leading to the“cytokine storm”,the aggravated immune response that indiscriminately perseveres,rampaging the host’s vital organs.Sedentary lifestyle,age-related hormonal imbalance,and adiposity induced inflammation predispose the body to the immune collapse following Covid-19 invasion,spotlighting the detrimental aftermath of metabolic dysfunction,and excess food consumption provoked by elevated cortisol and dysregulated appetite hormones.ACE 2 expression is suppressed in the skeletal muscle,rendering fitness and weight management an effective Covid-19 preventive intervention,along with social distancing,hygiene,and facial coverings.Physical activity,or exercise alternative methods have recently demonstrated statistically significant reductions of the inflammatory marker C-Reactive Protein(CRP),triglycerides,visceral fat,cortisol and the orexigenic hormone ghrelin,juxtaposed by optimal increases of IGF-1,skeletal muscle mass,Free T3,HDL,and the anorexic hormone leptin.
文摘During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.
基金Supported by Science and Technology Department Project of Jilin Province,China,No.20230101163JCthe Outstanding Youth Fund Project of Jilin Provincial Department of Education,China,No.JJKH20241324KJ.
文摘Coronavirus disease 2019(COVID-19)is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).SARS-CoV-2 infection typically presents with fever and respiratory symptoms,which can progress to severe respiratory distress syndrome and multiple organ failure.In severe cases,these complications may even lead to death.One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response.Therefore,suppressing the overactive immune response may be an effective strategy for treating COVID-19.Mesenchymal stem cells(MSCs)and their derived exosomes(MSCs-Exo)have potent homing abilities,immunomodulatory functions,regenerative repair,and antifibrotic effects,promising an effective tool in treating COVID-19.In this paper,we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19.We also summarize relevant recent clinical trials,including the source of cells,the dosage and the efficacy,and the clinical value and problems in this field,providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.
基金Supported by the European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the most recent global health threat,is spreading throughout the world with worrisome speed,and the current wave of coronavirus disease 2019(COVID-19)seems to have no mercy.While this mysterious virus challenges our ability to control viral infections,our opportunities to control the COVID-19 pandemic are gradually fading.Currently,pandemic management relies on preventive interventions.Although prevention is a good strategy to mitigate SARS-CoV-2 transmission,it still cannot be considered an absolute solution to eliminate this pandemic.Currently,developing a potent immunity against this viral infection seems to be the most promising strategy to drive down this ongoing global tragedy.However,with the emergence of new challenges in the context of immune responses to COVID-19,the road to control this devastating pandemic seems bumpier;thus,it is pivotal to characterize the dynamics of host immune responses to COVID-19,in order to develop efficient prophylactic and therapeutic tools.This begs the question of whether the effector mechanisms of the immune system are indeed potent or a possible contributing factor to developing more severe and lethal forms of COVID-19.In this review,the possible role of the immunopathologic phenomena including antibody-dependent enhancement,cytokine storm,and original antigenic sin in severity and mortality of COVID-19 will be discussed.
文摘The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)was identified in December 2019,in Wuhan,China.The virus was rapidly spread worldwide,causing coronavirus disease 2019(COVID-19)pandemic.Although COVID-19 is presented,usually,with typical respiratory symptoms(i.e.,dyspnea,cough)and fever,extrapulmonary manifestations are also encountered.Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and,even,acute liver failure.The pathogenesis of liver damage is not clearly defined;multiple mechanisms contribute to liver disorder,including direct cytopathic viral effect,cytokine storm and immune-mediated hepatitis,hypoxic injury,and druginduced liver toxicity.Patients with underlying chronic liver disease(i.e.,cirrhosis,non-alcoholic fatty liver disease,alcohol-related liver disease,hepatocellular carcinoma,etc.)may have greater risk to develop both severe COVID-19 and further liver deterioration,and,as a consequence,certain issues should be considered during disease management.The aim of this review is to present the prevalence,clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection.Moreover,we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.
