scholarly journals Pathogenesis of COVID-19: ACE2, Cytokine Storm and Extrapulmonary Manifestations

2021 ◽  
Vol 2 (4) ◽  
pp. 9
Author(s):  
Muhammad Naeem ◽  
Abdul Muhaymin Muhaymin ◽  
Hyder Wajid Abbasi ◽  
Naeem Ullah ◽  
Adnan Haider ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Entry ◽  
Distress Syndrome ◽  
Clinical Manifestations ◽  
First Century ◽  
Infected Person ◽  
Alveolar Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Taste And Smell

The coronavirus disease 19 (COVID-19) is a global pandemic of the twenty-first century and currently fourthwave is creating fear and panic worldwide. It is caused by severe acute respiratory syndrome coronavirus 2(SARS-COV-2), a highly contagious viral infection of humans. The COVID-19 can be spread mainly throughrespiratory droplet particles and in contact with a COVID-19 infected person. Clinical manifestation of COVID-19patients includes cough, fever, diarrhea, loss of taste and smell. In critical cases of COVID-19, the developmentof pneumonia and dyspnea leads to acute respiratory distress syndrome that may cause the death of thepatient. It is well established that Angiotensin-Converting Enzyme 2 (ACE2) receptors on alveolar cells act as anentry gate for the SARS-COV-2. However, ACE2 is also highly expressed in multiple extrapulmonary vital organssuch as the gastrointestinal system, cardiovascular system, kidney, etc. Therefore, the direct viral entry in theseorgans can be a likely pathway of injury. In addition, decoupling of immune responses leads to the cytokinesstorm, which might contribute to the injury of extrapulmonary organs. In this review, we report the multipleorgan pathogenesis and clinical manifestations of COVID-19 patients, which could aid clinicians and researchersin prioritizing therapeutics remedies and developing research for all vital body systems involved.

scholarly journals Metabolic Syndrome “Interacts” With COVID-19

2020 ◽  
Author(s):  
Zeling Guo ◽  
Shanping Jiang ◽  
Zilun Li ◽  
Sifan Chen
Keyword(s):  
Metabolic Disorders ◽  
Distress Syndrome ◽  
Metabolic Diseases ◽  
Clinical Manifestations ◽  
Severe Pneumonia ◽  
Symptomatic Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Treatment And Prevention ◽  
Global Pandemic ◽  
Metabolic Comorbidities

COVID-19, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emerged as a global pandemic and poses a great threat to public health and society in general. SARS-CoV-2 invades cells via its spike protein, which initiates endocytosis via its binding to host receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion after being cleaved by the serine protease, TMPRSS2. The most common clinical manifestations are fever, dry cough, fatigue and abnormalities on chest computed tomography (CT). However, some patients rapidly progress to severe pneumonia and develop acute respiratory distress syndrome (ARDS). Furthermore, SARS-CoV-2 triggers a severe cytokine storm, which may explain the deterioration of pre-existing metabolic disorders. Interestingly, conversely, underlying metabolic-related diseases, including hypertension, diabetes, cardiovascular disease, etc., are associated with progression and poor prognosis of COVID-19. The putative mechanisms are dysregulation of ACE2, impaired immunity especially uncontrolled hyperinflammation, hypercoagulability, etc. In this review, we summarize the crosstalk between COVID-19 and metabolic diseases and propose that in addition to controlling COVID-19, more intensive attention should be paid to the symptomatic treatment and prevention of pre-existing and foreseeable metabolic comorbidities.

scholarly journals SARS-CoV-2 and Viral Sepsis: Immune Dysfunction and Implications in Kidney Failure

2020 ◽  
Vol 9 (12) ◽  
pp. 4057
Author(s):  
Alessandra Stasi ◽  
Giuseppe Castellano ◽  
Elena Ranieri ◽  
Barbara Infante ◽  
Giovanni Stallone ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Viral Entry ◽  
Distress Syndrome ◽  
Cardiac Injury ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Cardiovascular Complications ◽  
Angiotensin Converting Enzyme 2 ◽  
Cytopathic Effects ◽  
Pro Inflammatory Cytokines

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), first emerged in Wuhan, China. The clinical manifestations of patients infected with COVID-19 include fever, cough, and dyspnea, up to acute respiratory distress syndrome (ARDS) and acute cardiac injury. Thus, a lot of severe patients had to be admitted to intensive care units (ICU). The pathogenic mechanisms of SARS-CoV-2 infection are mediated by the binding of SARS-CoV-2 spikes to the human angiotensin-converting enzyme 2 (ACE-2) receptor. The overexpression of human ACE-2 is associated with the disease severity in SARS-CoV-2 infection, demonstrating that viral entry into cells is a pivotal step. Although the lung is the organ that is most commonly affected by SARS-CoV-2 infection, acute kidney injury (AKI), heart dysfunction and abdominal pain are the most commonly reported co-morbidities of COVID-19. The occurrence of AKI in COVID-19 patients might be explained by several mechanisms that include viral cytopathic effects in renal cells and the host hyperinflammatory response. In addition, kidney dysfunction could exacerbate the inflammatory response started in the lungs and might cause further renal impairment and multi-organ failure. Mounting recent evidence supports the involvement of cardiovascular complications and endothelial dysfunction in COVID-19 syndrome, in addition to respiratory disease. To date, there is no vaccine, and no specific antiviral medicine has been shown to be effective in preventing or treating COVID-19. The removal of pro-inflammatory cytokines and the shutdown of the cytokine storm could ameliorate the clinical outcome in severe COVID-19 cases. Therefore, several interventions that inhibit viral replication and the systemic inflammatory response could modulate the severity of the renal dysfunction and increase the probability of a favorable outcome.

scholarly journals Cell-Mimicking Nanodecoys Protect Lung Cells by Neutralization of SARS-CoV-2 Spike Proteins

2020 ◽  
Author(s):  
Zhenhua Li ◽  
Phuong-Uyen C. Dinh ◽  
Kristen D. Popowski ◽  
Halle Lutz ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Viral Entry ◽  
Human Lung ◽  
Spike Protein ◽  
Inhalation Therapy ◽  
Viral Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Non Invasive ◽  
Global Pandemic ◽  
Integral Role

Abstract Coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown into a global pandemic, with no specific antiviral treatments or vaccines are yet approved. The viral receptor, angiotensin-converting enzyme 2 (ACE2), has been demonstrated to play an integral role in the pathogenesis of SARS-CoV-2, necessary for host cell viral entry. Inspired by this, we synthesized ACE2 nanodecoys from human lung spheroid cells (LSCs) capable of binding the Spike protein as a potential neutralization agent for SARS-CoV-2. Our results show LSC-nanodecoys has a high affinity and neutralization efficiency to both spike protein and chemically synthesized SARS-CoV-2 mimics. In addition, non-invasive inhalation therapy in mice showed successful delivery of the nanodecoy to the lungs, as well as in-vivo retention of the nanodecoys over 72 hours after a single administration. Furthermore, inhalation of nanodecoy accelerated the clearance of SARS-CoV-2 mimics from the lung and did not cause toxicity.

scholarly journals Histopathological features of SARS-CoV-2 infection and relationships with organoid technology

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110443
Author(s):  
İrem İnanç ◽  
Esra Erdemli
Keyword(s):  
Viral Entry ◽  
Three Dimensional ◽  
Human Cells ◽  
Host Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Antiviral Compounds ◽  
Global Pandemic ◽  
Species Specific

Coronavirus disease 2019 (COVID-19) following infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic that is still having serious effects worldwide. This virus, which targets the lungs in particular, can also damage other tissues. Angiotensin converting enzyme 2 (ACE-2) plays a key role in viral entry into host cells. The presence of ACE-2 in various tissues may permit viral infection. Studies of COVID-19 often make use of postmortem tissues. Although this information provides various useful results, it is also necessary to conduct in vitro studies to understand optimal treatment approaches. Because the virus may show species-specific differences, in vitro technologies using human cells are particularly important. Organoid technologies, three-dimensional structures that can be obtained from human cells, are playing increasingly important roles in studies of SARS-CoV-2. This technology offers a significant advantage in terms of mimicking in vivo tissue structures and testing antiviral compounds. In this mini-review, we summarize studies of SARS-CoV-2 using both histopathological and organoid technology approaches.

scholarly journals COVID-19: Current Understanding of Pathophysiology

2020 ◽  
Vol 18 (3) ◽  
pp. 351-359
Author(s):  
Gentle Sunder Shrestha ◽  
Sushil Khanal ◽  
Sachit Sharma ◽  
Gaurav Nepal
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory System ◽  
Patient Management ◽  
Distress Syndrome ◽  
Organ System ◽  
Current Understanding ◽  
Future Research ◽  
Effective Management ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic

Coronavirus disease 2019 has emerged as a global pandemic, affecting millions of people across the globe. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human cell after binding to the Angiotensin-Converting Enzyme 2 receptors, that are present in various organs. The involvement of the respiratory system is common and may progress to acute respiratory distress syndrome. Besides the involvement of respiratory system other systems like cardiovascular, renal, gastrointestinal and central nervous are not uncommon. In-depth understanding of the pathophysiological basis of organs and systems involvement and disease progression aids in the safe and effective management of the COVID-19 patients. It also helps to guide future well-designed clinical trials, which is the need of time. This review aims to explore the current understanding of pathophysiological basis of various organ system involvement in patients with COVID-19, that can have relevance for patient management and future research. We reviewed the articles in various databases to assemble the current evidences. Keywords: Coronavirus disease 2019; COVID-19; pathophysiology; severe acute respiratory syndrome coronavirus 2

scholarly journals Human Stem Cell Models of SARS-CoV-2 Infection in the Cardiovascular System

2021 ◽  
Author(s):  
Kyle Ernzen ◽  
Aaron J. Trask ◽  
Mark E. Peeples ◽  
Vidu Garg ◽  
Ming-Tao Zhao
Keyword(s):  
Cardiovascular System ◽  
Myocardial Injury ◽  
Clinical Manifestations ◽  
Angiotensin Converting Enzyme 2 ◽  
Coronary Syndrome ◽  
Differentiated Cells ◽  
Global Pandemic ◽  
Bidirectional Relationship ◽  
Stem Cell Models ◽  
Pro Inflammatory Cytokines

AbstractThe virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 190 million people to date, causing a global pandemic. SARS-CoV-2 relies on binding of its spike glycoprotein to angiotensin-converting enzyme 2 (ACE2) for infection. In addition to fever, cough, and shortness of breath, severe cases of SARS-CoV-2 infection may result in the rapid overproduction of pro-inflammatory cytokines. This overactive immune response is known as a cytokine storm, which leads to several serious clinical manifestations such as acute respiratory distress syndrome and myocardial injury. Cardiovascular disorders such as acute coronary syndrome (ACS) and heart failure not only enhance disease progression at the onset of infection, but also arise in hospitalized patients with COVID-19. Tissue-specific differentiated cells and organoids derived from human pluripotent stem cells (hPSCs) serve as an excellent model to address how SARS-CoV-2 damages the lungs and the heart. In this review, we summarize the molecular basis of SARS-CoV-2 infection and the current clinical perspectives of the bidirectional relationship between the cardiovascular system and viral progression. Furthermore, we also address the utility of hPSCs as a dynamic model for SARS-CoV-2 research and clinical translation. Graphical abstract

scholarly journals Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection

2020 ◽  
Author(s):  
Jeonghwan Youk ◽  
Taewoo Kim ◽  
Kelly V. Evans ◽  
Young-Il Jeong ◽  
Yongsuk Hur ◽  
...  
Keyword(s):  
Viral Entry ◽  
Three Dimensional ◽  
3D Culture ◽  
Transcriptome Profiling ◽  
Culture Technique ◽  
Alveolar Type ◽  
Alveolar Cells ◽  
Global Pandemic ◽  
Cell Transcriptome

AbstractSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases.

scholarly journals Neutrophils to Lymphocytes Ratio and the Prognosisof the COVID-19 Patients

2021 ◽  
Vol 3 (2) ◽  
pp. 86-96
Author(s):  
Mahsa Taghavi-Farahabadi ◽  
◽  
Mohammad Mahmoudi ◽  
Seyed Mahmoud Hashemi ◽  
Saeed Namaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Inflammation ◽  
Innate Immune ◽  
Lung Cells ◽  
Converting Enzyme ◽  
Innate Immune Responses ◽  
Alveolar Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Factors ◽  
Global Concern

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pandemic virus, a global concern, and has threatened human health. This virus binds to the Angiotensin-Converting Enzyme 2 (ACE2) that is expressed on different cells, especially on the alveolar cells. So the virus can enter the lung cells and causes respiratory syndromes. In Coronavirus Disease 2019 (COVID-19) that is caused by SARS-CoV-2, respiratory failure, and acute inflammation is the main cause of death. According to several reports, multiple factors, such as Neutrophils to Lymphocytes Ratio (NLR) have prognostic potentials in COVID-19. This study aims to review this parameter to have a better prediction about the condition of the patients and their treatments. According to this review, the NLR ratio that is related to the innate immune responses and inflammation can be helpful in the discrimination of severe from non-severe cases of COVID-19 patients.

scholarly journals Metabolic Syndrome and COVID 19: Endocrine-Immune-Vascular Interactions Shapes Clinical Course

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Rashika Bansal ◽  
Sriram Gubbi ◽  
Ranganath Muniyappa
Keyword(s):  
Metabolic Syndrome ◽  
Viral Entry ◽  
Clinical Manifestations ◽  
Microvascular Dysfunction ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Novel Coronavirus ◽  
Inflammatory Milieu ◽  
Pathophysiologic Mechanisms

Abstract The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Individuals with metabolic syndrome are at increased risk for poor disease outcomes and mortality from COVID-19. The pathophysiologic mechanisms for these observations have not been fully elucidated. A critical interaction between SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) facilitates viral entry into the host cell. ACE2 is expressed in pancreatic islets, vascular endothelium, and adipose tissue, and the SARS-CoV-2 -ACE2 interaction in these tissues, along with other factors, governs the spectrum and the severity of clinical manifestations among COVID-19 patients with metabolic syndrome. Moreover, the pro-inflammatory milieu observed in patients with metabolic syndrome may contribute toward COVID-19-mediated host immune dysregulation, including suboptimal immune responses, hyperinflammation, microvascular dysfunction, and thrombosis. This review describes the spectrum of clinical features, the likely pathophysiologic mechanisms, and potential implications for the management of metabolic syndrome in COVID-19 patients.

Repurposing Nimesulide, a Potent Inhibitor of the B0AT1 Subunit of the SARS-CoV-2 Receptor, as a Therapeutic Adjuvant of COVID-19

2020 ◽  
Vol 25 (10) ◽  
pp. 1171-1173 ◽  
Author(s):  
Mariafrancesca Scalise ◽  
Cesare Indiveri
Keyword(s):  
Viral Entry ◽  
3D Structure ◽  
World Health ◽  
Effective Vaccine ◽  
Target Cells ◽  
Physical Interaction ◽  
Disease Symptoms ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
Health Organization

The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.

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