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SARS-CoV-2 proteins

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    A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes MESHD

    Authors: Luiz Guilherme H.S. Aragao; Julia T Oliveira; Jairo R Temerozo; Mayara A Mendes; Jose Alexandre Salerno; Carolina da S. G. Pedrosa; Teresa Puig-Pijuan; Carla Verissimo; Isis M Ornelas; Thayana Torquato; Gabriela Vitoria; Carolina Q. Sacramento; Natalia Fintelman-Rodrigues; Suelen da Silva Gomes Dias; Vinicius Cardoso Soares; Leticia R. Q. Souza; Karina Karmirian; Livia Goto-Silva; Diogo Biagi; Estela M. Cruvinel; Rafael Dariolli; Daniel R. Furtado; Patricia T. Bozza; Helena L. Borges; Thiago Moreno L. Souza; Marilia Zaluar P. Guimaraes; Stevens Rehen

    doi:10.1101/2021.02.20.431855 Date: 2021-02-21 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 MESHD is myocardial injury MESHD, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 MESHD is the "cytokine storm", at which point the immune system malfunctions, leading to possible organ failure MESHD and death MESHD. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) on SARS-CoV-2-infected MESHD human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection MESHD and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha HGNC tumor necrosis factor-alpha MESHD ( TNF HGNC-) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage MESHD. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19 MESHD. HighlightsO_LIHuman iPSC-derived cardiomyocytes (hiPSC-CMs) express CB1 HGNC receptor. C_LIO_LIThe cannabinoid receptor agonist, WIN 55,212-2 (WIN), does not influence SARS-CoV-2 infection MESHD in hiPSC-CMs. C_LIO_LIWIN reduces inflammation MESHD and death MESHD in SARS-CoV-2-infected hiPSC-CMs MESHD. C_LI

    Clinical Characteristics and Risk Factors for Myocardial Injury and Arrhythmia in COVID-19 MESHD patients

    Authors: Hong Gang Ren; Xingyi Guo; Lei Tu; Qinyong Hu; Kevin Blighe; Luqman Bin Safdar; Justin Stebbing; Shepard D Weiner; Monte S Willis; Frits R Rosendaal; Guogang Xu; Feng Cao; Dao Weng Wang

    doi:10.1101/2020.11.30.20190926 Date: 2020-12-03 Source: medRxiv

    Background: Patients with COVID-19 MESHD can develop myocardial injury MESHD and arrhythmia MESHD during the course of their illness. However, the underlying risk factors for the development of cardiovascular related manifestations are unclear. Methods: Using a register-based multi-center cross-sectional design, we analyzed 80 patients with myocardial injury MESHD and 401 controls, as well as 71 patients with arrhythmia MESHD and 409 controls, all admitted with COVID-19 MESHD. Putative risk factors for myocardial injury MESHD and arrhythmia MESHD were evaluated with logistic regression with adjustment for potential confounders. Results: COVID-19 MESHD patients with myocardial injury had fatigue MESHD (66.2%) and dyspnea MESHD (63.7%), while those with arrhythmia had dyspnea MESHD (71.8%). Patients with myocardial injury MESHD and arrhythmia MESHD had a significant mortality of 92.5% and 94.4%, respectively. A history of chronic obstructive pulmonary disease MESHD ( COPD MESHD) or heart diseases MESHD was associated with an increased risk of myocardial injury MESHD (odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.01-3.71; OR = 7.43, 95% CI: 3.99-13.83) and arrhythmia MESHD (OR = 1.94, 95% CI: 1.00-3.75; OR = 13.16, 95% CI: 6.75-25.68). In addition, we found that gamma glutamyltranspeptidase (GGT) HGNC >50U/L (OR = 2.14, 95% CI: 1.37-3.32; OR = 1.85, 95% CI: 1.19-2.85), serum creatinine >111mol/L (OR = 8.96, 95% CI: 4.4-18.23; OR = 3.71, 95% CI: 2.01-6.85), serum sodium <136 mmol/L (OR = 4.68, 95% CI: 2.46-8.91; OR = 2.06; 95% CI: 1.06-4.00) were all associated with increased risk of myocardial injury MESHD and arrhythmia MESHD, respectively. Conclusion: Our reported clinical characteristics and identified risk factors are important for clinical study of COVID-19 MESHD patients developing myocardial injury MESHD and arrhythmia MESHD.

    SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 MESHD Myocarditis

    Authors: Adam L Bailey; Oleksandr Dmytrenko; Lina Greenberg; Andrea L Bredemeyer; Pan Ma; Jing Liu; Vinay Penna; Lulu Lai; Emma S Winkler; Sanja Sviben; Erin Brooks; Ajith P Nair; Kent A Heck; Aniket S Rali; Leo Simpson; Mehrdad Saririan; Dan Hobohm; W. Tom Stump; James A Fitzpatrick; Xuping Xie; Pei-Yong Shi; J Travis Hinson; Weng-Tein Gi; Constanze Schmidt; Florian Leuschner; Chieh-Yu Lin; Michael S Diamond; Michael J Greenberg; Kory J Lavine; Pamela J. Bjorkman; Saurabh Mehandru; Paul D. Bieniasz; Marina Caskey; Michel C. Nussenzweig

    doi:10.1101/2020.11.04.364315 Date: 2020-11-05 Source: bioRxiv

    Epidemiological studies of the COVID-19 MESHD COVID-19 MESHD pandemic have revealed evidence of cardiac involvement MESHD and documented that myocardial injury MESHD and myocarditis MESHD are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection MESHD. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection MESHD is dependent on expression of angiotensin-I converting enzyme 2 HGNC ( ACE2 HGNC) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis MESHD, including cardiomyocyte cell death, impaired cardiac contractility MESHD, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 MESHD myocarditis MESHD demonstrated cardiomyocyte infection MESHD, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19 MESHD.

    The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection MESHD

    Authors: Jessica Maiuolo; Rocco Mollace; Micaela Gliozzi; Vincenzo Musolino; Cristina Carresi; Sara Paone; Miriam Scicchitano; Roberta Macrì; Saverio Nucera; Francesca Bosco; Federica Scarano; Maria Caterina Zito; Stefano Ruga; Annamaria Tavernese; Vincenzo Mollace

    id:10.20944/preprints202010.0585.v1 Date: 2020-10-28 Source: Preprints.org

    Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection MESHD is associated, alongside with lung infection MESHD and respiratory disease MESHD, to cardiovascular dysfunction MESHD that occurs at any stage of the disease. This includes ischemic MESHD heart disease MESHD, arrhythmias MESHD, and cardiomyopathies MESHD. The common pathophysiological link between SARS-CoV-2 infection MESHD and the cardiovascular events is represented by coagulation abnormalities MESHD and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection MESHD, seems to represent the major target of SARS CoV-2 disease MESHD state and accounts for the systemic vascular dysfunction MESHD that leads to detrimental effect in terms of hospitalization and death accompanying the disease MESHD. In particular, the molecular interaction of SARS-CoV-2 with ACE2 HGNC receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation MESHD and thrombosis MESHD of peripheral blood vessels. This highlights systemic hypoxia MESHD and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection MESHD. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection MESHD. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 HGNC receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection MESHD are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

    Clinico-laboratory profile, intensive care needs, treatment details, and outcome of Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): A systematic review and Meta-analysis.

    Authors: Vijai Williams; Nabaneea Dash; Renu Suthar; Vichithra Mohandoss; Nishant Jaiswal; TK Kavitha; Karthi Nallasamy; Suresh Kumar Angurana

    doi:10.1101/2020.10.21.20217034 Date: 2020-10-25 Source: medRxiv

    Objectives: To synthesize the current data on clinico-laboratory features, intensive care needs, treatment, and outcome of Pediatric inflammatory multisystem syndrome MESHD temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome MESHD in children (MIS-C). Data Sources: Articles published in PubMed, Web of Science, Scopus, Google Scholar, and WHO COVID-19 MESHD research database, CDC database, and Cochrane COVID-19 MESHD study register between 1st December 2019 to 10th July 2020. Study Selection: Observational studies involving patients [≤]21 years with PIMS-TS or MIS-C, that reported the clinico-laboratory features, intensive care needs, treatment, and outcome. Data Extraction: The search identified 422 citations and finally 18 studies with 833 participants were included and pooled estimate was calculated for parameters of interest utilising random effect model. Data Synthesis: The median age was 9 (8-11) years. Fever MESHD, gastrointestinal symptoms MESHD, rash MESHD, conjunctival injection, and respiratory symptoms MESHD were common clinical features. Majority had positive SARS-CoV-2 antibody test and only 1/3rd had RT-PCR positive. The commonest laboratory abnormalities were elevated CRP, D-dimer, procalcitonin, BNP HGNC, fibrinogen HGNC, ferritin, troponin, and IL-6 HGNC; and lymphopenia MESHD, hypoalbuminemia MESHD, and thrombocytopenia MESHD. The cardiovascular complications included shock (65%), myocardial dysfunction MESHD (61%), myocarditis MESHD (65%), and coronary artery abnormalities MESHD (39%). Three-fourth children required admission in PICU for mechanical ventilation (25%) and vasoactive drugs (61%). The common treatment provided was IVIG (82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). The mortality was low (n=13). Conclusion: Fever MESHD, gastrointestinal MESHD and mucocutaneous symptoms, cardiac dysfunction MESHD, shock, and hyperinflammation are common manifestations of PIMS-TS or MIS-C. The short-term outcome is good with supportive intensive care and immunomodulatory treatment.

    CardiOvaScular Mechanisms MESHD In Covid-19 MESHD: Methodology of a prospective observational multimodality imaging study (COSMIC-19 study)

    Authors: Shirjel Alam; Anoop Shah; Kevin Onyinkwa; Edward Nganga; Samuel Gitau; Khalid Makhdomi; Michael Chung; Sudhir Vinayak

    doi:10.21203/rs.3.rs-77405/v2 Date: 2020-09-14 Source: ResearchSquare

    Background: 8-28% of patients infected with COVID-19 MESHD have evidence of cardiac injury MESHD, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury MESHD are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 MESHD infections.Methods: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 MESHD infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA & 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease MESHD will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease MESHD including presence of cardiac dysfunction MESHD, myocardial fibrosis MESHD, myocardial oedema MESHD and myocardial infarction MESHD. 18F-FDG-PET/CT will identify vascular and cardiac inflammation MESHD. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. Discussion: The results of the study will identify the presence and modality of cardiac injury MESHD associated COVID-19 MESHD infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION:          This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at www.isrctn.com/ISRCTN12154994

    Cardiac involvement in COVID-19 MESHD patients: mid-term follow up by cardiac magnetic resonance imaging

    Authors: Hui Wang; Ruili Li; Hong Jiang; Zixu Yan; Xinyan Tao; Hongjun Li; Lei Xu

    doi:10.21203/rs.3.rs-57104/v1 Date: 2020-08-11 Source: ResearchSquare

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) induces myocardial injury MESHD, either direct myocarditis MESHD or indirect injury due to systemic inflammatory response. Myocardial involvement MESHD has been proved to be one of the primary manifestations of COVID-19 MESHD infection, according to laboratory test, autopsy, and cardiac magnetic resonance imaging (CMRI). However, the middle-term outcome of cardiac involvement MESHD after the patients were discharged from the hospital is yet unknown. The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 MESHD patients by CMRIMethods: A total of 47 recovered COVID-19 MESHD patients were prospectively recruited and underwent CMRI examination in this study. The CMRI protocol consisted of black blood fat-suppressed T2 weighted imaging (BB-T2WI), T2 star mapping, left ventricle cine imaging, pre- and post-contrast T1 mapping, and late gadolinium enhancement (LGE). Myocardium edema MESHD and LGE were assessed in recovered COVID-19 MESHD patients. The left ventricle ( LV MESHD) and right ventricle (RV) function and LV mass were assessed and compared with normal controls.Results: Finally, 44 recovered COVID-19 MESHD patients and 31 normal controls were included in this study. No edema MESHD was observed in any patient. LGE was found in 13 patients. All LGE lesions were located in the middle myocardium and/or sub-epicardium with a scattered distribution. Further analysis showed that LGE-positive patients had significantly decreased left ventricle peak global circumferential strain (LVpGCS), right ventricle peak global circumferential strain (RVpGCS), right ventricle peak global longitudinal strain (RVpGLS) as compared to non-LGE patients (p<0.05), while no difference was detected between the non-LGE patients and normal controls.Conclusion: Myocardium injury MESHD existed in about 30% of COVID-19 MESHD patients. These patients had peak right ventricle strain that decreased at the 3-month follow-up. Cardiac MRI can monitor the COVID-19 MESHD-induced myocarditis MESHD progression, and CMR strain analysis is a sensitive tool to evaluate the recovery of left ventricle circumferential contraction dysfunction MESHD and right ventricular dysfunction MESHD.

    The Spectrum of Cardiovascular Complications in COVID-19 MESHD- A Comprehensive Literature Review

    Authors: Raja Shakeel Mushtaque; Rabia Mushtaque; Shahbano Baloch; Aadil Raza; Haseeb Bhatti; Zohaib Khan

    id:10.20944/preprints202008.0257.v1 Date: 2020-08-11 Source: Preprints.org

    A newly identified novel coronavirus named as severe acute respiratory syndrome MESHD-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 MESHD ( COVID-19 MESHD), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 HGNC (ACE2) receptor through surface glycoprotein (S PROTEIN protein). These ACE 2 HGNC receptors are attached to the cell membranes of many organs. Thus, COVID-19 MESHD does not only result in acute respiratory distress syndrome MESHD but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 MESHD can damage the myocardial cells and result in fulminant myocarditis MESHD, acute cardiac injury MESHD, cardiomyopathy MESHD, heart failure MESHD, cardiogenic shock MESHD, or arrhythmia MESHD. COVID-19 MESHD seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19 MESHD, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

    County-Level Longitudinal Clustering of COVID-19 MESHD Mortality to Incidence Ratio in the United States

    Authors: Nasim Vahabi; Masoud Salehi; Julio Duarte; Abolfazl Mollalo; George Michailidis

    doi:10.21203/rs.3.rs-40632/v2 Date: 2020-07-07 Source: ResearchSquare

    Background: As of November 12, 2020, the mortality to incidence ratio (M IR) HGNC of COVID-19 MESHD was 5.8% in the US. We utilized a longitudinal MESHD model-based clustering system based on the disease trajectories over time. We aimed to find the so-called “vulnerable” cluster of counties where to dedicate additional resources by the US policymakers.  Methods: County-level COVID-19 MESHD cases and deaths (Mar-Nov 2020), and a set of potential risk factors were collected for 3050 U.S. counties during the 1st wave (Mar25-Jun3, 2020), 1344 counties (sunbelt region) during the 2nd wave (Jun4-S ep2, HGNC 2020), and 1055 counties (great plains) during the 3rd wave (S ep3- HGNCNov12, 2020). We used growth mixture models to identify clusters of counties exhibiting similar COVID-19 MESHD M IR HGNCgrowth trajectories and risk-factors over time. Results: We identified the so-called “more vulnerable” clusters during the 1st, 2nd and 3rd waves of COVID-19 MESHD. Tuberculosis MESHD (OR=1.3-2.1-3.2), drug use disorder MESHD (OR=1.1), hepatitis MESHD (OR=13.1), HIV/AIDS MESHD (OR=2.3), cardiomyopathy MESHD and myocarditis MESHD (OR=1.3), diabetes MESHD (OR=1.2), mesothelioma MESHD (OR=9.3) were significantly associated with increased odds of being in a more vulnerable cluster. Heart complications MESHD and cancer MESHD were the main risk factors increasing the COVID-19 MESHD MIR (range: 0.08%-0.52% M IR↑ HGNC).Conclusion: We identified the so-called “more vulnerable” county-clusters exhibiting the highest COVID-19 MESHD MIR trajectories, indicating that enhancing the capacity and access to healthcare resources would be key to successfully manage COVID-19 MESHD in these clusters. These findings provide insights for public health policymakers on the groups of people and locations they need to pay particular attention while managing the COVID-19 MESHD epidemic.

    Baseline echocardiographic assessment of left ventricle kinetics alteration and mortality risk in a cohort of critically ill COVID-19 MESHD patients

    Authors: Davide Ceccato; Beatrice Gusella; Mattia Grassi; Alessandro Toffolon; Anna Postal; Davide Gorgi; Federico Capone; Alois Saller; Alberto Cipriani; Cristiano Sarais; Roberto Vettor; Raffaele Pesavento

    doi:10.21203/rs.3.rs-35798/v1 Date: 2020-06-15 Source: ResearchSquare

    Background SARS-CoV2 infection MESHD are frequently associated with cardiovascular manifestations, in particular with symptomatic acute coronary syndromes MESHD, cardiac arrhythmias MESHD and acute heart failure MESHD. However, the elevation of serum troponin seems to be non specific, and a cardiologic diagnostic workup should be performed. We aimed to assess the clinical characteristic and the prevalence of left ventricular (LV) dyssynergy patterns MESHD in a cohort of hospitalized non-critically ill COVID-19 MESHD patientsMethods Consecutive patients with an objective diagnosis of COVID-19 MESHD, from February to April 2020. Baseline characteristics and comorbidities was collected. In case of increased troponin levels or symptoms suggestive for a concomitant cardiac syndrome MESHD, patients undergo to serial electrocardiograms, serial Troponin tests and bedside transthoracic echocardiogram.Results 402 consecutive patients were enrolled: 55 patients underwent an echocardiographic exam because of an increase in troponin levels or a suspected myocardial injury MESHD. Segmental left ventricular abnormalities MESHD were found in 10 (median WMSI 2.03 IQR 1.38-2.75) with a median LV MESHD ejection fraction was 30.1 % IQR, median troponin level was 3083 ng/L, median BNP HGNC was 761 ng/L. Death for any cause occurred in 4 patients among patients with regional LV abnormalities MESHD and in 3 with normal regional function (p= 0,02).Discussion A single bedside transthoracic echocardiogram performed in non critically ill COVID-19 MESHD patients with suspected cardiac injury MESHD has the potential to better assist clinicians in their challenging decision process. As an isolated increase of troponin levels is common in COVID patients, a bed-side echocardiographic evaluation of cardiac function should be routinely implemented during their early evaluation.

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SARS-CoV-2 Proteins


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