Potential bangle (Zingiber montanum J.König) rhizome extract as a supplement to prevent and reduce symptoms of Covid-19

The morbidity and mortality rates due to Covid-19 are increasing day by day, to overcome this, we urgently need a better treatment strategy, therefore various ways and strategies for this must be pursued. The purpose of the present review is to explain that the rhizome of bangle (Zingiber montanum) has great potential to increase antibodies and reduce symptoms of acute respiratory distress syndrome (ARDS), which also seems suitable for treating Covid-19. Method: This review is looking for the results of scientific research from various sources, regarding the efficacy of bangle (Zingiber montanum) rhizome which is strongly suspected to be able to prevent, and reduce the symptoms that occur in COVID-19. The results showed that the bangle rhizome extract had activity as immunomodulatory, antiviral and reduced symptoms such as what happened in COVID-19. Conclusion: Bangle rhizome extract has dozens of nutritious substances and has multifunctional activities, and it can be postulated that among the benefits of bangle rhizome extract it is able to prevent and reduce symptoms that occur in Covid-19, and preclinical studies and clinical studies are needed to prove this postulate.     

Stem cell therapy in coronavirus disease 2019: current evidence and future potential

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.     

Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential

The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data.     

Clinical progress in MSC-based therapies for the management of severe COVID-19

Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.     

Potential influence of Nagella sativa (Black cumin) in reinforcing immune system: A hope to decelerate the COVID-19 pandemic

The world is witnessing a difficult time. The race of developing a new coronavirus (COVID-19) vaccine is becoming more urgent. Many preliminary studies on the pathophysiology of COVID-19 patients have provided some clues to treat this pandemic. However, no suitable treatment has found yet. Various symptoms of patients infected with COVID-19 indicated the importance of immune regulation in the human body. Severe cases admitted to the intensive care unit showed high level of pro-inflammatory cytokines which enhanced the disease severity. Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients is another critical factor of disease severity and mortality. So, Immune modulation is the only way of regulating immune system. Nigella sativa has been used for medicinal purposes for centuries. The components of this plant are known for its intense immune-regulatory, anti-inflammatory, and antioxidant benefits in obstructive respiratory disorders. A molecular docking study also gave evidences that N. sativa decelerates COVID-19 and might give the same or better results than the FDA approved drugs. The aim of this review was to investigate the possible immune-regulatory effects of N. sativa on COVID-19 pandemic. Our review found N. sativa's Thymoquinone, Nigellidine, and α-hederin can be a potential influencer in reinforcing the immune response on molecular grounds.     

The role of CD4+FoxP3+ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment

The severe cases of Coronavirus Disease 2019 (COVID-19) frequently exhibit excessive inflammatory responses, acute respiratory distress syndrome (ARDS), coagulopathy, and organ damage. The most striking immunopathology of advanced COVID-19 is cytokine release syndrome or “cytokine storm” that is attributable to the deficiencies in immune regulatory mechanisms. CD4⁺FoxP3⁺ regulatory T cells (Tregs) are central regulators of immune responses and play an indispensable role in the maintenance of immune homeostasis. Tregs are likely involved in the attenuation of antiviral defense at the early stage of infection and ameliorating inflammation-induced organ injury at the late stage of COVID-19. In this article, we review and summarize the current understanding of the change of Tregs in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the potential role of Tregs in the immunopathology of COVID-19. The emerging concept of Treg-targeted therapies, including both adoptive Treg transfer and low dose of IL-2 treatment, is introduced. Furthermore, the potential Treg-boosting effect of therapeutic agents used in the treatment of COVID-19, including dexamethasone, vitamin D, tocilizumab and sarilumab, chloroquine, hydroxychloroquine, azithromycin, adalimumab and tetrandrine, is discussed. The problems in the current study of Treg cells in COVID-19 and future perspectives are also addressed.     

A single centered study reveals association between liver injury and COVID-19 infection

Background and aimDespite the fact that it has been over a year with the pandemic COVID-19 infection, ongoing research and analysis reveal many complications and comorbidities associated with COVID-19. In this study, we aimed at investigating the clinical and laboratory assessments in COVID-19 patients with and without liver injury.MethodsSymptomatic 541 COVID-19 positive patients, who were admitted to Al Kuwait Hospital, Dubai, United Arab Emirates (UAE), were recruited in this study. Their data was collected retrospectively, including demographic data, blood tests, symptoms, radiographical assessments, and clinical outcomes of COVID-19.ResultsAround 19% of the recruited COVID-19 patients displayed signs of acute liver injury. Also, there was an increase in the percentage of critical, ICU-admitted and mortality rates in COVID-19 cases with liver injury, as well as a higher percentage of septic shock and acute respiratory distress syndrome (ARDS). COVID-19 patients with liver injury had more pronounced bilateral consolidation, lymphopenia and neutrophilia. Additionally, these patients had higher levels of CRP, LDH, procalcitonin, ferritin and D dimer levels. Finally, there was a higher percentage of patients taking various COVID-19 therapies in the COVID-19 patients with liver injury group.ConclusionCOVID-19 patients with acute liver injury are at a higher risk for serious outcomes including death.     

Dysregulation of the immune response in coronavirus disease 2019

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger a cytokine storm in the pulmonary tissue by releasing various types of mediators, leading to acute respiratory distress syndrome (ARDS). Increased neutrophil-to-lymphocyte ratio, as well as CD4+ T lymphopenia, is reported in cases with novel coronavirus disease (COVID-19), meanwhile, lymphopenia is a significant finding in the majority of COVID-19 cases with a severe phenotype. Moreover, excessive activation of monocyte/macrophage and cytokine storms are associated with the severity of the disease and the related complications in SARS-CoV-2 infection. Understanding the immune response dysregulation in COVID-19 is essential to develop more effective diagnostic, therapeutic, and prophylactic strategies in this pandemic.     

益生菌缓解新型冠状病毒感染症状的研究进展

由急性呼吸道综合征冠状病毒2(severeacuterespiratorysyndromecoronavirus2,SARS-CoV-2)引起的新型冠状病毒感染(coronavirusdisease2019,COVID-19)从2020年初迅速扩展至全球,成为人类历史上最严重的大流行之一。已有证据证明当SARS-CoV-2的刺突蛋白(S蛋白)与细胞表面受体血管紧张素转化酶2 (angiotensin converting enzyme 2, ACE2)结合时,可感染宿主细胞,引起肠道菌群失调,并引发不同的并发症。益生菌是活的微生物,已被证明对人体健康有益。因其在调节肠道菌群、治疗多种疾病和抗病毒方面的功效而被考虑用来改善COVID-19。本文基于目前公开的临床前和临床试验结果,总结了益生菌在缓解COVID-19临床症状及胃肠道不良反应的效果,并讨论了益生菌在改善COVID-19后遗症方面的潜力,从而为后续管理COVID-19提供新的方向,进一步为呼吸系统疾病提供理论依据。     

Beta-Adrenergic Blockers as a Potential Treatment for COVID-19 Patients

More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the “ARAS loop”) is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo .     

A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a ‘Cytokine Super Cyclone’. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of ‘trained immunity’ in early protection against SARS-CoV2.     

The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system

In 2019–2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called “cytokine storm” an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.     

Neuroinflammation and COVID-19

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.     

A Comprehensive Review of Animal Models for Coronaviruses: SARS-CoV-2, SARS-CoV,and MERS-CoV

The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.     

Recent progress and prospects for anti-cytokine therapy in preclinical and clinical acute lung injury

Acute respiratory distress syndrome (ARDS) is a heterogeneous cause of respiratory failure that has a rapid onset, a high mortality rate, and for which there is no effective pharmacological treatment. Current evidence supports a critical role of excessive inflammation in ARDS, resulting in several cytokines, cytokine receptors, and proteins within their downstream signalling pathways being putative therapeutic targets. However, unsuccessful trials of anti-inflammatory drugs have thus far hindered progress in the field. In recent years, the prospects of precision medicine and therapeutic targeting of cytokines coevolving into effective treatments have gained notoriety. There is an optimistic and growing understanding of ARDS subphenotypes as well as advances in treatment strategies and clinical trial design. Furthermore, large trials of anti-cytokine drugs in patients with COVID-19 have provided an unprecedented amount of information that could pave the way for therapeutic breakthroughs. While current clinical and nonclinical ARDS research suggest relatively limited potential in monotherapy with anti-cytokine drugs, combination therapy has emerged as an appealing strategy and may provide new perspectives on finding safe and effective treatments. Accurate evaluation of these drugs, however, also relies on well-founded experimental research and the implementation of biomarker-guided stratification in future trials. In this review, we provide an overview of anti-cytokine therapy for acute lung injury and ARDS, highlighting the current preclinical and clinical evidence for targeting the main cytokines individually and the therapeutic prospects for combination therapy.     

Assessment of global asymptomatic SARS-CoV-2 infection and management practices from China

With ongoing research, it was found that asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was widespread in coronavirus disease 2019 (COVID-19) populations. Studies have confirmed asymptomatic patients with COVID-19 have potential infectivity, and most of the transmission occurred before symptoms appear. Asymptomatic infection rates varied widely in different countries and regions. Identifying the asymptomatic infected persons and cutting off the infection source is an effective way to prevent the spread of this disease. However, asymptomatic patients have hidden clinical symptoms, and screening based only on the clinical symptoms of COVID-19 can easily lead to a missed diagnosis. Therefore, determining asymptomatic infection patients by SARS-CoV-2 nucleic acid testing is the gold standard. A series of prevention and control measures adopted by the Chinese government, especially the “Four Early” policy, have achieved outstanding achievements, which are worth learning from by other countries.     

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies

Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.     

Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has reached worldwide pandemic proportions, causing coronavirus disease 2019 (COVID-19). The clinical manifestations of COVID-19 vary from an asymptomatic disease course to clinical symptoms of acute respiratory distress syndrome and severe pneumonia. The lungs are the primary organ affected by SARS-CoV-2, with a very slow turnover for renewal. SARS-CoV-2 enters the lungs via angiotensin-converting enzyme 2 receptors and induces an immune response with the accumulation of immunocompetent cells, causing a cytokine storm, which leads to target organ injury and subsequent dysfunction. To date, there is no effective antiviral therapy for COVID-19 patients, and therapeutic strategies are based on experience treating previously recognized coronaviruses. In search of new treatment modalities of COVID-19, cell-based therapy with mesenchymal stem cells (MSCs) and/or their secretome, such as soluble bioactive factors and extracellular vesicles, is considered supportive therapy for critically ill patients. Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin, including alveolar epithelial cells, lung epithelial cells, and vascular endothelial cells, which are severely damaged in the course of COVID-19 disease. Moreover, MSCs secrete a variety of bioactive factors that can be applied for respiratory tract regeneration in COVID-19 patients thanks to their trophic, anti-inflammatory, immunomodulatory, anti-apoptotic, pro-regenerative, and proangiogenic properties.     

The NLRP3 inflammasome and COVID-19: Activation,pathogenesis and therapeutic strategies

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called “cytokine storm”. Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.     

Pathogenesis and treatment of cytokine storm in COVID-19

COVID-19 is a viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that killed a large number of patients around the world. A hyperinflammatory state resulting in a cytokine storm and adult respiratory distress syndrome seems to be the major cause of the death. Many mechanisms have been suggested in the pathogenesis of COVID-19 associated cytokine storm (COVID-CS). Insufficient viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity seem to be the main mechanisms underlying the pathogenesis. The diagnosis of COVID-19 is based on relatively constant clinical symptoms, clinical findings, laboratory tests, and imaging techniques, while the diagnosis of COVID-CS is a rather dynamic process, based on evolving or newly emerging findings during the clinical course. Management of COVID-19 consists of using antiviral agents to inhibit SARS-CoV-2 replication and treating potential complications including the cytokine storm together with general supportive measures. COVID-CS may be treated using appropriate immunosuppressive and immunomodulatory drugs that reduce the level of inappropriate systemic inflammation, which has the potential to cause organ damage. Currently corticosteroids, IL-6 blockers, or IL-1 blockers are most widely used for treating COVID-CS.