scholarly journals The Role of MSC Therapy in Attenuating the Damaging Effects of the Cytokine Storm Induced by COVID-19 on the Heart and Cardiovascular System

2020 ◽  
Vol 7 ◽  
Author(s):  
Georgina M. Ellison-Hughes ◽  
Liam Colley ◽  
Katie A. O'Brien ◽  
Kirsty A. Roberts ◽  
Thomas A. Agbaedeng ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Cardiovascular Complications ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Cell Therapies ◽  
Tissue Repair And Regeneration ◽  
Global Pandemic ◽  
Organ Systems

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has led to 47 m infected cases and 1. 2 m (2.6%) deaths. A hallmark of more severe cases of SARS-CoV-2 in patients with acute respiratory distress syndrome (ARDS) appears to be a virally-induced over-activation or unregulated response of the immune system, termed a “cytokine storm,” featuring elevated levels of pro-inflammatory cytokines such as IL-2, IL-6, IL-7, IL-22, CXCL10, and TNFα. Whilst the lungs are the primary site of infection for SARS-CoV-2, in more severe cases its effects can be detected in multiple organ systems. Indeed, many COVID-19 positive patients develop cardiovascular complications, such as myocardial injury, myocarditis, cardiac arrhythmia, and thromboembolism, which are associated with higher mortality. Drug and cell therapies targeting immunosuppression have been suggested to help combat the cytokine storm. In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.

scholarly journals Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19

2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  
Keyword(s):  
Organ Damage ◽  
Multiple Organ ◽  
Global Pandemic ◽  
Organ Systems ◽  
Future Challenges ◽  
The Central Nervous System ◽  
The Impact ◽  
Collaborative Efforts ◽  
The Brain

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.

scholarly journals COVID-19 related mortality in post-operative cardiac surgical patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Azhar Hussain ◽  
Amina Khalil ◽  
Priyanka Kolvekar ◽  
Prity Gupta ◽  
Shyamsunder Kolvekar
Keyword(s):  
Cardiac Surgery ◽  
Long Term Outcomes ◽  
Case Presentation ◽  
Elective Cardiac Surgery ◽  
The United Kingdom ◽  
Global Pandemic ◽  
Cardiac Operations ◽  
Related Mortality

Abstract Background COVID-19 has caused a global pandemic of unprecedented proportions. Elective cardiac surgery has been universally postponed with only urgent and emergency cardiac operations being performed. The National Health Service in the United Kingdom introduced national measures to conserve intensive care beds and significantly limit elective activity shortly after lockdown. Case presentation We report two cases of early post-operative mortality secondary to COVID-19 infection immediately prior to the implementation of these widespread measures. Conclusion The role of cardiac surgery in the presence of COVID-19 is still very unpredictable and further studies on both short term and long term outcomes are warranted.

scholarly journals Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms

2021 ◽  
Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  
Keyword(s):  
Decision Making ◽  
Male Patient ◽  
Young Male ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Invasive Ventilation ◽  
Organ Systems ◽  
The Central Nervous System

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.

scholarly journals Pediatric Antiphospholipid Syndrome: from Pathogenesis to Clinical Management

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Silvia Rosina ◽  
Cecilia Beatrice Chighizola ◽  
Angelo Ravelli ◽  
Rolando Cimaz
Keyword(s):  
Antiphospholipid Syndrome ◽  
Fluid Phase ◽  
Multiple Organ ◽  
Clinical Settings ◽  
Glycoprotein I ◽  
Long Term Follow Up ◽  
Pediatric Populations ◽  
Cellular Components

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.

scholarly journals Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results

2020 ◽  
Author(s):  
Peter A Kavsak ◽  
Ola Hammarsten ◽  
Andrew Worster ◽  
Stephen W Smith ◽  
Fred S Apple
Keyword(s):  
North America ◽  
Severe Acute Respiratory Syndrome ◽  
Cardiovascular System ◽  
Cardiac Troponin ◽  
Long Term Care ◽  
Prognostic Indicator ◽  
Term Care ◽  
Testing Strategies

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged late in 2019 causing COVID-19 (coronavirus disease-2019) may adversely affect the cardiovascular system. Publications from Asia, Europe, and North America have identified cardiac troponin as an important prognostic indicator for patients hospitalized with COVID-19. We recognized from publications within the first 6 months of the pandemic that there has been much uncertainty on the reporting, interpretation, and pathophysiology of an increased cardiac troponin concentration in this setting. Content The purpose of this mini-review is: a) to review the pathophysiology of SARS-CoV-2 and the cardiovascular system, b) to overview the strengths and weaknesses of selected studies evaluating cardiac troponin in patients with COVID-19, and c) to recommend testing strategies in the acute period, in the convalescence period and in long-term care for patients who have become ill with COVID-19. Summary This review provides important educational information and identifies gaps in understanding the role of cardiac troponin and COVID-19. Future, properly designed studies will hopefully provide the much-needed evidence on the path forward in testing cardiac troponin in patients with COVID-19.

scholarly journals HCMV Infection and Apoptosis: How Do Monocytes Survive HCMV Infection?

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 533 ◽  
Author(s):  
Donna Collins-McMillen ◽  
Liudmila Chesnokova ◽  
Byeong-Jae Lee ◽  
Heather Fulkerson ◽  
Reynell Brooks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Survival ◽  
Hcmv Infection ◽  
Viral Gene Expression ◽  
Multiple Organ ◽  
Viral Gene ◽  
Blood Monocytes ◽  
Induced Differentiation ◽  
Organ Systems

Human cytomegalovirus (HCMV) infection of peripheral blood monocytes plays a key role in the hematogenous dissemination of the virus to multiple organ systems following primary infection or reactivation of latent virus in the bone marrow. Monocytes have a short life span of 1–3 days in circulation; thus, HCMV must alter their survival and differentiation to utilize these cells and their differentiated counterparts—macrophages—for dissemination and long term viral persistence. Because monocytes are not initially permissive for viral gene expression and replication, HCMV must control host-derived factors early during infection to prevent apoptosis or programmed cell death prior to viral induced differentiation into naturally long-lived macrophages. This review provides a short overview of HCMV infection of monocytes and describes how HCMV has evolved to utilize host cell anti-apoptotic pathways to allow infected monocytes to bridge the 48–72 h viability gate so that differentiation into a long term stable mature cell can occur. Because viral gene expression is delayed in monocytes following initial infection and only occurs (begins around two to three weeks post infection in our model) following what appears to be complete differentiation into mature macrophages or dendritic cells, or both; virally-encoded anti-apoptotic gene products cannot initially control long term infected cell survival. Anti-apoptotic viral genes are discussed in the second section of this review and we argue they would play an important role in long term macrophage or dendritic cell survival following infection-induced differentiation.

scholarly journals SARS-CoV-2, ACE2 expression, and systemic organ invasion

2020 ◽  
Author(s):  
Usman M Ashraf ◽  
Ahmed A Abokor ◽  
Jonnelle M. Edwards ◽  
Emily W. Waigi ◽  
Rachel S. Royfman ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Normal Function ◽  
Multiple Organ ◽  
Angiotensin Converting Enzyme 2 ◽  
Multiple Organs ◽  
Global Pandemic ◽  
Organ Systems ◽  
Novel Coronavirus ◽  
Severe Respiratory Illness ◽  
Organ Invasion

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

scholarly journals Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

2020 ◽  
Vol 7 ◽  
Author(s):  
Francesca Salamanna ◽  
Melania Maglio ◽  
Maria Paola Landini ◽  
Milena Fini
Keyword(s):  
Multiple Organ ◽  
Host Cells ◽  
Specific Patient ◽  
Angiotensin Converting Enzyme 2 ◽  
Body Distribution ◽  
Organ Failures ◽  
Personalized Approach ◽  
Potential Interactions

The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.

Cardiovascular effects of treadmill exercise in physiological and pathological preclinical settings

2011 ◽  
Vol 300 (6) ◽  
pp. H1983-H1989 ◽  
Author(s):  
Cinzia Perrino ◽  
Giuseppe Gargiulo ◽  
Gianluigi Pironti ◽  
Anna Franzone ◽  
Laura Scudiero ◽  
...  
Keyword(s):  
Treadmill Exercise ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Multiple Organ ◽  
Organ Systems ◽  
Physiological Cardiac Hypertrophy ◽  
Models Of Disease ◽  
Acute Changes ◽  
Exercise In Humans

Exercise adaptations result from a coordinated response of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunologic, and skeletal muscle. Among these, the cardiovascular system is the most directly affected by exercise, and it is responsible for many of the important acute changes occurring during physical training. In recent years, the development of animal models of pathological or physiological cardiac overload has allowed researchers to precisely analyze the complex cardiovascular responses to stress in genetically altered murine models of human cardiovascular disease. The intensity-controlled treadmill exercise represents a well-characterized model of physiological cardiac hypertrophy because of its ability to mimic the typical responses to exercise in humans. In this review, we describe cardiovascular adaptations to treadmill exercise in mice and the most important parameters that can be used to quantify such modifications. Moreover, we discuss how treadmill exercise can be used to perform physiological testing in mouse models of disease and to enlighten the role of specific signaling pathways on cardiac function.

scholarly journals Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system

2009 ◽  
Vol 296 (1) ◽  
pp. H13-H28 ◽  
Author(s):  
Boglarka Laczy ◽  
Bradford G. Hill ◽  
Kai Wang ◽  
Andrew J. Paterson ◽  
C. Roger White ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Cardiovascular System ◽  
Protein Modification ◽  
Cell Function ◽  
Cardiovascular Function ◽  
Cardiovascular Complications ◽  
Protective Mechanisms ◽  
Cytoplasmic Proteins ◽  
Present Understanding

The posttranslational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide β- N-acetylglucosamine ( O-GlcNAc) is a highly dynamic and ubiquitous protein modification. Protein O-GlcNAcylation is rapidly emerging as a key regulator of critical biological processes including nuclear transport, translation and transcription, signal transduction, cytoskeletal reorganization, proteasomal degradation, and apoptosis. Increased levels of O-GlcNAc have been implicated as a pathogenic contributor to glucose toxicity and insulin resistance, which are both major hallmarks of diabetes mellitus and diabetes-related cardiovascular complications. Conversely, there is a growing body of data demonstrating that the acute activation of O-GlcNAc levels is an endogenous stress response designed to enhance cell survival. Reports on the effect of altered O-GlcNAc levels on the heart and cardiovascular system have been growing rapidly over the past few years and have implicated a role for O-GlcNAc in contributing to the adverse effects of diabetes on cardiovascular function as well as mediating the response to ischemic injury. Here, we summarize our present understanding of protein O-GlcNAcylation and its effect on the regulation of cardiovascular function. We examine the pathways regulating protein O-GlcNAcylation and discuss, in more detail, our understanding of the role of O-GlcNAc in both mediating the adverse effects of diabetes as well as its role in mediating cellular protective mechanisms in the cardiovascular system. In addition, we also explore the parallels between O-GlcNAc signaling and redox signaling, as an alternative paradigm for understanding the role of O-GlcNAcylation in regulating cell function.

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