scholarly journals Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men

2020 ◽  
Author(s):  
Zaniar Ghazizadeh ◽  
Homa Majd ◽  
Mikayla Richter ◽  
Ryan Samuel ◽  
Seyedeh Maryam Zekavat ◽  
...  
Keyword(s):  
Troponin T ◽  
Severe Disease ◽  
Treatment Options ◽  
Cardiac Injury ◽  
Embryonic Stem ◽  
Screening Strategy ◽  
Cardiac Cells ◽  
Alveolar Epithelial Cells ◽  
Host Cell Membrane ◽  
Health Crisis

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.

scholarly journals Transcription Factor Lbx1 Expression in Mouse Embryonic Stem Cell-Derived Phenotypes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Stefanie Schmitteckert ◽  
Cornelia Ziegler ◽  
Liane Kartes ◽  
Alexandra Rolletschek
Keyword(s):  
Transcription Factor ◽  
Developmental Stages ◽  
Troponin T ◽  
Es Cells ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Cardiac Cells ◽  
Cell Stage

Transcription factor Lbx1 is known to play a role in the migration of muscle progenitor cells in limb buds and also in neuronal determination processes. In addition, involvement of Lbx1 in cardiac neural crest-related cardiogenesis was postulated. Here, we used mouse embryonic stem (ES) cells which have the capacity to develop into cells of all three primary germ layers. Duringin vitrodifferentiation, ES cells recapitulate cellular developmental processes and gene expression patterns of early embryogenesis. Transcript analysis revealed a significant upregulation ofLbx1at the progenitor cell stage. Immunofluorescence staining confirmed the expression of Lbx1 in skeletal muscle cell progenitors and GABAergic neurons. To verify the presence of Lbx1 in cardiac cells, triple immunocytochemistry of ES cell-derived cardiomyocytes and a quantification assay were performed at different developmental stages. Colabeling of Lbx1 and cardiac specific markers troponin T, α-actinin, GATA4, and Nkx2.5 suggested a potential role in early myocardial development.

scholarly journals COVID-19 Convalescent plasma

Blood ◽  
2021 ◽  
Author(s):  
Aaron Tobian ◽  
Claudia S Cohn ◽  
Beth Shaz
Keyword(s):  
Therapeutic Potential ◽  
High Titer ◽  
Severe Disease ◽  
Treatment Options ◽  
The United States ◽  
Trial Data ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Health Crisis ◽  
Viral Neutralization ◽  
Elderly Outpatients

As the coronavirus disease (COVID-19) pandemic led to a global health crisis, there were limited treatment options and no prophylactic therapies for those exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Convalescent plasma is quick to implement, potentially provides benefits, and has a good safety profile. The therapeutic potential of COVID-19 convalescent plasma (CCP) is likely mediated by antibodies through direct viral neutralization and Fc-dependent functions such as a phagocytosis, complement activation, and antibody-dependent cellular cytotoxicity. In the United States, CCP became one of the most common treatments with over half million units transfused despite limited efficacy data. More than a dozen randomized trials now demonstrate that CCP does not provide benefit for those with moderate to severe disease. However, similar to other passive antibody therapies, CCP is beneficial for early disease, when provided to elderly outpatients within 72 hours after symptom onset. Only high-titer CCP should be transfused. CCP should also be considered for immunosuppressed COVID-19 patients. CCP collected in proximity, by time and location, to the patient may be more beneficial due to SARS-CoV-2 variants. Additional randomized trial data are still accruing and should be incorporated with other trial data to optimize CCP indications.

scholarly journals Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection

2020 ◽  
Vol 319 (5) ◽  
pp. H1059-H1068
Author(s):  
Fulton A. Robinson ◽  
Ryan. P. Mihealsick ◽  
Brant M. Wagener ◽  
Peter Hanna ◽  
Megan D. Poston ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Severe Disease ◽  
Cardiac Injury ◽  
Cardiac Cells ◽  
Cardiac Complications ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Metabolic Demand ◽  
Angiotensin Converting Enzyme 2

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by preexisting cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin-converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang-(1–7) but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.

scholarly journals COVID-19 in obstetrics 2020: the experience at a New York City medical center

2020 ◽  
Vol 48 (9) ◽  
pp. 892-899
Author(s):  
Ashlesha K. Dayal ◽  
Armin S. Razavi ◽  
Amir K. Jaffer ◽  
Nishant Prasad ◽  
Daniel W. Skupski
Keyword(s):  
New York ◽  
Medical Center ◽  
Severe Disease ◽  
Infection Rates ◽  
Health Crisis ◽  
The Public ◽  
Public Health Crisis ◽  
Asymptomatic Carriage ◽  
Global Spread ◽  
Workforce Flexibility

AbstractThe global spread of the SARS-CoV-2 virus during the early months of 2020 was rapid and exposed vulnerabilities in health systems throughout the world. Obstetric SARS-CoV-2 disease was discovered to be largely asymptomatic carriage but included a small rate of severe disease with rapid decompensation in otherwise healthy women. Higher rates of hospitalization, Intensive Care Unit (ICU) admission and intubation, along with higher infection rates in minority and disadvantaged populations have been documented across regions. The operational gymnastics that occurred daily during the Covid-19 emergency needed to be translated to the obstetrics realm, both inpatient and ambulatory. Resources for adaptation to the public health crisis included workforce flexibility, frequent communication of operational and protocol changes for evaluation and management, and application of innovative ideas to meet the demand.

scholarly journals Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany

Infection ◽  
2021 ◽  
Author(s):  
Johanna Koehler ◽  
Barbara Ritzer ◽  
Simon Weidlich ◽  
Friedemann Gebhardt ◽  
Chlodwig Kirchhoff ◽  
...  
Keyword(s):  
High Risk ◽  
Tertiary Care Hospital ◽  
Severe Disease ◽  
Treatment Options ◽  
Tertiary Care ◽  
Antibody Therapy ◽  
Additional Treatment ◽  
Care Hospital ◽  
Cross Sectional ◽  
Asymptomatic Patients

AbstractAdditional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

scholarly journals 549. Clinical Characteristics and Outcomes of Patients with COVID-19 treated with Convalescent Plasma in Miami, Florida

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S340-S341
Author(s):  
Shweta Anjan ◽  
Dimitra Skiada ◽  
Miriam Andrea Duque Cuartas ◽  
Douglas Salguero ◽  
David P Serota ◽  
...  
Keyword(s):  
Treatment Options ◽  
Disease Outbreaks ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Health Crisis ◽  
Infectious Disease Outbreaks ◽  
Reactive Protein ◽  
High Acuity ◽  
Us Fda ◽  
Oxygen Requirements

Abstract Background The Coronavirus disease of 2019 (COVID-19) global health crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in unprecedented mortality, impacted society, and strained healthcare systems, yet sufficient data regarding treatment options are lacking. Convalescent plasma, used since 1895 for infectious disease outbreaks, offers promise as a treatment option for COVID-19. Methods This is a retrospective study of patients diagnosed by a nasopharyngeal swab SARS-CoV-2 reverse transcriptase–polymerase chain reaction (RT-PCR), who received convalescent plasma between April to June 2020 at two large hospitals in Miami, Florida, as part of the US FDA Expanded Access Program for COVID-19 convalescent plasma (CCP). Results A total of 23 patients received CCP, 13 (57%) had severe COVID-19 disease, while 8 (35%) had critical or critical with multiorgan dysfunction. Median time of follow up was 26 (range, 7–79) days. Overall, 11 (48%) survived to discharge, 6 (26%) died, while 6 (26%) are currently hospitalized. All deaths reported were due to septic shock from secondary infections. 15 (65%) showed improvement in oxygen requirements 7 days post CCP transfusion. Measured inflammatory markers, c-reactive protein, lactate dehydrogenase, ferritin and d-dimer improved 7 days post transfusion in 13 (57%) patients. No adverse events due to the transfusion were reported. 10 (43.4%) patients had a negative SARS-CoV-2 RT-PCR at a median of 14.5 (range, 4–31) days after receiving convalescent plasma. Conclusion Administration of convalescent plasma was found to be safe, with favorable outcomes in this small cohort of relatively high acuity patients. Larger studies including control arms are needed to establish the efficacy of convalescent plasma on clinical and virologic outcomes for patients with COVID-19. Table Disclosures All Authors: No reported disclosures

scholarly journals COVID-19 cardiac injury and the use of colchicine

2021 ◽  
Vol 14 (2) ◽  
pp. e241047
Author(s):  
Vanesa Anton-Vazquez ◽  
Laura Byrne ◽  
Lisa Anderson ◽  
Lisa Hamzah
Keyword(s):  
Sinus Tachycardia ◽  
Inflammatory Responses ◽  
Troponin T ◽  
Systolic Function ◽  
Cardiac Injury ◽  
T Wave ◽  
Wave Inversion ◽  
Ventricular Extrasystoles

We report a case of cardiac injury in a 46-year-old man affected by COVID-19. The patient presented with shortness of breath and fever. ECG revealed sinus tachycardia with ventricular extrasystoles and T-wave inversion in anterior leads. Troponin T and N-terminal pro B-type natriuretic peptide were elevated. Transthoracic echocardiography showed severely reduced systolic function with an estimated left ventricle ejection fraction of 30%. A nasopharingeal swab was positive for SARS-CoV-2. On day 6, 11 days after onset of symptoms, the patient deteriorated clinically with new chest pain and type 1 respiratory failure. Treatment with colchicine 0.5 mg 8-hourly resulted in rapid clinical resolution. This case report highlights how cardiac injury can dominate the clinical picture in COVID-19 infection. The role of colchicine therapy should be further studied to determine its usefulness in reducing myocardial and possibly lung parenchymal inflammatory responses.

Anti Pyretic and Analgesic activity of Herbal Formulation: I mplications in managing COVID-19 Fever

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1873-1878
Author(s):  
Palep H S ◽  
Swati patil ◽  
Snehal funde ◽  
Ankur phalak
Keyword(s):  
Severe Disease ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Laboratory Animals ◽  
Antipyretic Effect ◽  
Genetic Sequencing ◽  
Herbal Formulation ◽  
Inflammatory Drugs ◽  
Sepsis And Septic Shock ◽  
Mild Fever

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Genetic sequencing of the virus suggests that it is a beta coronavirus closely linked to the SARS virus. While most people with COVID-19 develop the only mild or uncomplicated illness, approximately 14% develop a severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by acute respiratory distress syndrome (ARDS), sepsis and septic shock, multi organ failure, including acute kidney injury and cardiac injury. Reports of the pattern of Covid symptoms suggest that mild fever, cold and cough are the most common symptoms on an average by 5 days after exposure to the virus. Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. There is enough literature to prove that many molecules from plants have shown important therapeutic activity with lesser side effects as compared to conventional medicines. Therefore, the present study is aimed to evaluate Plant extracts of proven antiviral activity, which are described as antipyretics and analgesics in classical Ayurvedic texts for their analgesic & antipyretic effect in laboratory animals. Tab. Febcin formulation was selected.

Abstract 304: Efficient Generation of Cardiac Purkinje Fiber-like Cells From ESCs by Activating cAMP Signaling

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Su-Yi Tsai ◽  
Karen Maass ◽  
Jia Lu ◽  
Glenn I Fishman ◽  
Shuibing Chen ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Cardiac Cells ◽  
Cardiac Conduction ◽  
Camp Signaling ◽  
Purkinje Fiber ◽  
Mechanistic Studies ◽  
Cardiac Progenitors ◽  
Gene Profiles ◽  
Novel Strategy ◽  
Regenerative Therapies

Dysfunction of the cardiac conduction system (CCS) significantly impacts pathogenesis of arrhythmia, a major cause of morbidity and mortality. Strategies to derive cardiac conduction cells including Purkinje fiber cells (PC) would facilitate models for mechanistic studies and drug discovery, and also provide new cellular materials for regenerative therapies. A high-throughput chemical screen using CCS:lacZ and Contactin2:eGFP (Cntn2:eGFP) reporter embryonic stem cell (ESC) lines was used to discover a small molecule, sodium nitroprusside (SN), that efficiently promotes the generation of cardiac cells that express gene profiles and generate action potentials of PC-like cells. Imaging and mechanistic studies suggest that SN promotes the generation of PC from cardiac progenitors initially expressing cardiac myosin heavy chain, and that it does so by activating cAMP signaling. These findings provide a novel strategy to derive scalable PC, along with insight into the ontogeny of CCS development.

scholarly journals Mechanistic Inferences from Clinical Reports of SARS-CoV-2

2020 ◽  
Author(s):  
Meagan M Jenkins ◽  
Tyler R McCaw ◽  
Paul A Goepfert
Keyword(s):  
Randomized Clinical Trials ◽  
Severe Disease ◽  
Treatment Options ◽  
Management Strategies ◽  
Type I ◽  
Interferon Signaling ◽  
Adaptive Responses ◽  
Initial Clinical Trial ◽  
Inflammatory State ◽  
Clinical Trial Results

SARS-CoV-2 was identified as the causative pathogen in an outbreak of viral pneumonia cases originating in Wuhan, China, with an ensuing rapid global spread that led it to be declared a pandemic by the WHO on March 11, 2020. Given the threat to public health posed by sequelae of SARS-CoV-2 infection, the literature surrounding patient presentation in severe and non-severe cases, transmission rates and routes, management strategies, and initial clinical trial results have become available at an unprecedented pace. In this review we collate current clinical and immunologic reports, comparing these to reports of previous coronaviruses to identify mechanisms driving progression to severe disease in some patients. In brief, we propose a model wherein dysregulated type I interferon signaling leads to aberrant recruitment and accumulation of innate immune lineages in the lung, impairing establishment of productive adaptive responses, and permitting a pathologic pro-inflammatory state. Finally, we extend these findings to suggest possible treatment options that may merit investigation in randomized clinical trials.

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