Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

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COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives.

The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

Biomarkers associated with COVID-19 disease progression.

Background and purpose The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19. Data sources We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied. Study selection and data extraction We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome. Results We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score). Conclusion Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes. Systematic review registration Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.

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Prognostic Factors for Severity and Mortality in Patients Infected with COVID-19: A Systematic Review

Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study.

Rationale: Initial reports of case fatality rates (CFRs) among adults with coronavirus disease (COVID-19) receiving invasive mechanical ventilation (IMV) are highly variable.Objectives: To examine the CFR of patients with COVID-19 receiving IMV.Methods: Two authors independently searched PubMed, Embase, medRxiv, bioRxiv, the COVID-19 living systematic review, and national registry databases. The primary outcome was the "reported CFR" for patients with confirmed COVID-19 requiring IMV. "Definitive hospital CFR" for patients with outcomes at hospital discharge was also investigated. Finally, CFR was analyzed by patient age, geographic region, and study quality on the basis of the Newcastle-Ottawa Scale.Measurements and Results: Sixty-nine studies were included, describing 57,420 adult patients with COVID-19 who received IMV. Overall reported CFR was estimated as 45% (95% confidence interval [CI], 39-52%). Fifty-four of 69 studies stated whether hospital outcomes were available but provided a definitive hospital outcome on only 13,120 (22.8%) of the total IMV patient population. Among studies in which age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI, 46.4-49.4%) in younger patients (age ≤40 yr) to 84.4% (95% CI, 83.3-85.4%) in older patients (age >80 yr). CFR was also higher in early COVID-19 epicenters. Overall heterogeneity is high (I2 >90%), with nonsignificant Egger's regression test suggesting no publication bias.Conclusions: Almost half of patients with COVID-19 receiving IMV died based on the reported CFR, but variable CFR reporting methods resulted in a wide range of CFRs between studies. The reported CFR was higher in older patients and in early pandemic epicenters, which may be influenced by limited ICU resources. Reporting of definitive outcomes on all patients would facilitate comparisons between studies.Systematic review registered with PROSPERO (CRD42020186997).

Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis.

Low-intensity focused ultrasound guided dodecafluoropentane-loaded acoustic phase-change nanoparticles for treatment of porcine coronary microthromboembolism.

Ultrasound-controlled nano oxygen carriers enhancing cell viability in 3D GelMA hydrogel for the treatment of myocardial infarction.

The probability of toxicity-related myocardial injury event with anthracyclines is controversial, which could be related to the underlying cardiac status before chemotherapy. Our study sought to investigate the influence of cardiovascular risk factors on myocardial motion and cardiac function using layer-specific speckle tracking echocardiography (STE) during chemotherapy with epirubicin. Female patients with first-diagnosed breast cancer were prospectively enrolled in our study and received 4 chemotherapeutic cycles with epirubicin in each cycle of 21 days. All patients underwent echocardiography for layer-specific STE analysis before and after all chemotherapy. Clinical data including cardiovascular risk factors were collected. According to the Framingham score, patients with cardiovascular risk factors were divided into groups with low, medium, and high risk. 134 patients existed in the final analysis. The accumulated dose of epirubicin for were 560.0 ± 103.8 mg. 97 (72.4%) patients had cardiovascular risk factors. According to the Framingham score, 57 (42.5%) patients categorized in high risk. Endocardial layer strain after chemotherapy were lower than those at baseline (p < 0.05, all), especially for patients with high risk. The changes of endocardial longitudinal strain during chemotherapy were associated with cardiovascular risks at baseline with correlation coefficient of 0.627. Our study found that layer-specific STE is valuable for early detection of toxicity-related myocardial injury for patients with breast cancer after epirubicin chemotherapy and cardiovascular risk factors have greatly influenced on cardiac function during chemotherapy. The endocardial layer strain is sensitive to evaluate early-stage toxicity-related myocardial injury after epirubicin chemotherapy.

Value of layer-specific speckle tracking echocardiography for early detection of myocardial injury caused by chemotherapy in breast cancer patients with cardiovascular risk

Bo Hu

Papers

Low-intensity focused ultrasound guided dodecafluoropentane-loaded acoustic phase-change nanoparticles for treatment of porcine coronary microthromboembolism.

Ultrasound-controlled nano oxygen carriers enhancing cell viability in 3D GelMA hydrogel for the treatment of myocardial infarction.

Value of layer-specific speckle tracking echocardiography for early detection of myocardial injury caused by chemotherapy in breast cancer patients with cardiovascular risk