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

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

Download Full-text

Exercise Training and Cardiac Rehabilitation in COVID-19 Patients with Cardiovascular Complications: State of Art

Life ◽

10.3390/life11030259 ◽

2021 ◽

Vol 11 (3) ◽

pp. 259

Author(s):

Mariaconsiglia Calabrese ◽

Marina Garofano ◽

Roberta Palumbo ◽

Paola Di Pietro ◽

Carmine Izzo ◽

...

Keyword(s):

Exercise Training ◽

Cardiac Rehabilitation ◽

Cardiovascular System ◽

Patient Monitoring ◽

Scientific Evidence ◽

Cardiovascular Complications ◽

Angiotensin Converting Enzyme 2 ◽

Coronary Syndrome ◽

Cardiovascular Damage ◽

Include Heart Failure

Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.

Download Full-text

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

Life and Science ◽

10.37185/lns.1.1.199 ◽

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.

Download Full-text

Mechanisms of Damage to the Cardiovascular System in COVID-19

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1474 ◽

2021 ◽

Vol 76 (3) ◽

pp. 287-297

Author(s):

Alexandr Y. Fisun ◽

Yuriy V. Lobzin ◽

Dmitry V. Cherkashin ◽

Vadim V. Tyrenko ◽

Konstantin N. Tkachenko ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiovascular System ◽

Heart Muscle ◽

Cardiac Death ◽

Myocardial Damage ◽

Angiotensin Converting Enzyme 2 ◽

Coronary Syndrome ◽

Life Threatening ◽

Potential Benefits ◽

Myocardial Involvement

The review article is devoted to the analysis of the literature on the various mechanisms of damage to the cardiovascular system in COVID-19. The article briefly outlines the epidemiology and urgency of the COVID-19 problem, describes the features of the clinical picture of heart muscle damage in COVID-19. The pathophysiology, morphology and pathogenetic mechanisms of myocardial involvement in cases of SARS-CoV-2 lesion are considered in detail. The authors present a diagram of various mechanisms of myocardial damage in COVID-19, which includes mediated damage to the heart muscle through angiotensin-converting enzyme 2, myocardial damage caused by hypoxemia, microvascular heart damage, and systemic inflammatory response syndrome. A detailed scheme of cardiomyocyte infection with the involvement of cytokines, which ultimately leads to myocardial remodeling and dilated cardiomyopathy, is presented. The pathophysiological foundations of the development of sudden cardiac death in COVID-19, which include the mechanisms of life-threatening arrhythmias, acute coronary syndrome, and heart failure, are considered. The authors analyzed scientific studies of the toxic effects of COVID-19 drug treatment on the heart muscle, in particular, antiviral, antibacterial, antimalarial agents. Their potential benefits and harms, as well as the likelihood of developing cardiovascular events, in particular sudden cardiac death, were assessed.

Download Full-text

Metabolic Syndrome “Interacts” With COVID-19

BIO Integration ◽

10.15212/bioi-2020-0035 ◽

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.

Download Full-text

COVID-19 and Cardiovascular Complications: An Updated Review

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.7235 ◽

2021 ◽

Vol 9 (F) ◽

pp. 712-719

Author(s):

Januar Wibawa Martha

Keyword(s):

Myocardial Injury ◽

Treatment Strategies ◽

Cardiovascular Complications ◽

Cytokine Release ◽

Interval Prolongation ◽

Coronary Syndrome ◽

Qt Interval Prolongation ◽

Coagulation Abnormalities ◽

Global Pandemic ◽

Plaque Destabilization

COVID-19 has become a global pandemic. Patients with pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease (CVD) are associated with greater severity and higher mortality. COVID-19 can cause cardiovascular complications, including myocardial injury, myocarditis, heart failure, acute coronary syndrome, and coagulation abnormalities. Possible pathophysiology and molecular pathways driving these disease processes are cytokine release syndrome, RAAS system dysregulation, plaque destabilization and coagulation disorders Myocarditis is one concern among persons who received mRNA-Based COVID-19 vaccines. There are several cardiovascular complications that are possibly caused by COVID-19 treatments, such as QT interval prolongation, arrhythmia, and hypotension. Due to increasingly recognized CVD damage in COVID-19, we need to understand about COVID-19 related to cardiovascular complications and treatment strategies.

Download Full-text

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

Journal of Clinical Medicine ◽

10.3390/jcm9124057 ◽

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.

Download Full-text

Dampak Coronavirus Disease 2019 terhadap Sistem Kardiovaskular

e-CliniC ◽

10.35790/ecl.v8i2.30540 ◽

2020 ◽

Vol 8 (2) ◽

Author(s):

Herick A. Willim ◽

Infan Ketaren ◽

Alice I. Supit

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Myocardial Injury ◽

Clinical Manifestations ◽

Cardiovascular Complications ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Cardiovascular Comorbidity ◽

Cardiovascular Comorbidities ◽

Severe Manifestation

Abstract: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has become a pandemic. Patient with cardiovascular comorbidity has a higher risk of suffering more severe manifestation of COVID-19 associated with a higher mortality. Although dominated by respiratory clinical manifestation, COVID-19 may also cause severe cardiovascular disorders. Angiotensin converting enzyme 2 (ACE2) acts as a receptor of SARS-CoV-2. Patients of COVID-19 with cardiovascular comorbidities may experience more severe clinical manifestations, presumably due to higher ACE2 expression in this population. Cardiovascular complications in COVID-19 may include myocardial injury, myocarditis, acute myocardial infarction, acute heart failure, thromboembolism, and arrhythmias. Therefore, optimization of conservative medical therapy needs to be prioritized in patients with cardiovascular comorbidities. Emergency intervention can be considered in certain cases with hemodynamic instability.Keywords: cardiovascular system, COVID-19, SARS-CoV-2, ACE2 Abstrak: Coronavirus disease 2019 (COVID-19) telah merupakan pandemi yang disebabkan oleh infeksi Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Pasien dengan komorbid kardiovaskular berisiko lebih tinggi untuk mengalami manifestasi yang lebih berat jika terinfeksi COVID-19 dan berhubungan dengan mortalitas yang lebih tinggi. Meskipun didominasi oleh manifestasi klinis respiratorik, COVID-19 juga dapat menyebabkan gangguan kardiovaskular yang berat. Angiotensin converting enzyme 2 (ACE2) berperan sebagai reseptor SARS-CoV-2. Diduga pasien dengan penyakit kardiovaskular dapat bermanifestasi klinis lebih berat karena ekspresi ACE2 yang lebih tinggi pada populasi ini. Komplikasi kardiovaskular pada COVID-19 dapat meliputi jejas miokardium, miokarditis, infark miokard akut, gagal jantung akut, tromboemboli, dan aritmia. Pada pasien dengan komorbid kardiovaskular, optimalisasi terapi medis konservatif perlu diprioritaskan. Tindakan intervensi darurat dapat dipertimbangkan pada kasus tertentu dengan instabilitas hemodinamik.Kata kunci: sistem kardiovaskular, COVID-19, SARS-CoV-2, ACE2

Download Full-text

Pain as clinical manifestations of COVID-19 infection and its management in the pandemic era: a literature review

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-020-00258-0 ◽

2020 ◽

Vol 56 (1) ◽

Author(s):

I. Putu Eka Widyadharma ◽

Ni Nyoman Shinta Prasista Sari ◽

Kadek Enny Pradnyaswari ◽

Kadek Tresna Yuwana ◽

I. Putu Gede Danika Adikarya ◽

...

Keyword(s):

Neuropathic Pain ◽

Clinical Manifestations ◽

Management Approach ◽

Angiotensin Converting Enzyme 2 ◽

Muscular Pain ◽

Global Pandemic ◽

Stomach Pain ◽

Treatment Continuity ◽

Case Number

AbstractCoronavirus disease 2019 (COVID-19) is a current global pandemic. The case number has increased since December 31, 2019. It has been reported that COVID-19 patients have been giving pain complaints, one of which is muscular pain. Other types of pain that have also been reported by COVID-19 patients are joint pain, stomach pain, and testicular pain. Neuropathic pain is the rarest case among others. COVID-19 mechanisms in the nerve and musculoskeletal damage are believed to be caused by the expression and distribution of angiotensin-converting enzyme 2 (ACE-2). Patients with pain, especially neuropathic pain, normally do not respond well to various therapies, and experience psychiatric disorders such as depression, which leads to a decrease in the patient’s quality of life. Important considerations for health professionals in terms of pain management during this pandemic include ensuring treatment continuity, painkillers, utilization of telemedicine, biopsychosocial management approach, and modifying therapy needs to reduce the risks of COVID-19 complications.

Download Full-text

Coronavirus disease: a global problem of the 21st century

Complex Issues of Cardiovascular Diseases ◽

10.17802/2306-1278-2020-9-2-6-16 ◽

2020 ◽

Vol 9 (2) ◽

pp. 6-16

Author(s):

E. D. Bazdyrev

Keyword(s):

Infectious Disease ◽

Cardiovascular System ◽

21St Century ◽

Causative Agent ◽

Clinical Manifestations ◽

Diagnosis And Treatment ◽

Global Problem ◽

Global Pandemic ◽

Acute Infectious Disease ◽

The Impact

A series of unexplained cases with pneumonia have been reported in China since December 2019. Subsequent studies have found a novel strain of coronavirus, SARS-CoV-2, as the causative agent of acute infectious disease that has been named as coronavirus disease 2019 (COVID-19). COVID-19 has outbroken as a global pandemic affecting over 200 countries. This review focuses on a novel coronovirus disease, reporting all available data on its etiology, epidemiology, pathogenesis, clinical manifestations, principles of diagnosis and treatment. In addition, the impact of COVID on the cardiovascular system is highlighted.

Download Full-text

Pediatric COVID-19 and the Factors That May Mitigate Its Clinical Course

Journal of Child Science ◽

10.1055/s-0040-1717077 ◽

2020 ◽

Vol 10 (01) ◽

pp. e137-e140

Author(s):

Mosaad Abdel-Aziz ◽

Nada M. Abdel-Aziz ◽

Dina M. Abdel-Aziz ◽

Noha Azab

Keyword(s):

Clinical Features ◽

Clinical Symptoms ◽

Clinical Course ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Angiotensin Converting Enzyme 2 ◽

Compulsory Vaccination ◽

Specific Factors ◽

Novel Coronavirus ◽

Radiographic Data

AbstractThe clinical manifestations of novel coronavirus disease 2019 (COVID-19) vary from mild flu-like symptoms to severe fatal pneumonia. However, children with COVID-19 may be asymptomatic or may have mild clinical symptoms. The aim of this study was to investigate clinical features of pediatric COVID-19 and to search for the factors that may mitigate the disease course. We reviewed the literature to realize the clinical features, laboratory, and radiographic data that may be diagnostic for COVID-19 among children. Also, we studied the factors that may affect the clinical course of the disease. Fever, dry cough, and fatigue are the main symptoms of pediatric COVID-19, sometimes flu-like symptoms and/or gastrointestinal symptoms may be present. Although some infected children may be asymptomatic, a recent unusual hyperinflammatory reaction with overlapping features of Kawasaki's disease and toxic shock syndrome in pediatric COVID-19 has been occasionally reported. Severe acute respiratory syndrome-coronvirus-2 (SARS-CoV-2) nucleic acid testing is the corner-stone method for the diagnosis of COVID-19. Lymphocyte count and other inflammatory markers are not essentially diagnostic; however, chest computed tomography is highly specific. Factors that may mitigate the severity of pediatric COVID-19 are home confinement with limited children activity, trained immunity caused by compulsory vaccination, the response of the angiotensin-converting enzyme 2 receptors in children is not the same as in adults, and that children are less likely to have comorbidities. As infected children may be asymptomatic or may have only mild respiratory and/or gastrointestinal symptoms that might be missed, all children for families who have a member diagnosed with COVID-19 should be investigated.

Download Full-text