Risk Factors and Mechanisms of Cardiovascular Diseases in Posttraumatic Stress Disorder Model in Wistar Rats as Dependent on Stress Resistance and Age.

The article focuses on the pathogenetic mechanisms of posttraumatic stress disorder (PTSD), which is associated with psychological stress because of the coronavirus pandemic. The molecular mechanisms responsible for disease susceptibility in some individuals and stress resistance in others are amongst crucial research interests of experimental and clinical medicine. Priority data were obtained to indicate that distortions of synthesis and metabolism and, most significantly, a switch between two energy transport forms, glucose and lipids, underlie myocardial dysfunction in young and old stress-sensitive Wistar rats in a PTSD model. Histochemistry and polarization microscopy showed energy deficit in cardiomyocytes and signs of ischemic and hypoxic areas emerging in the myocardium as a result of an accumulation of NADH and NADPH, which initiate excessive production of reactive oxygen species.

Levels and predictors of fear and health anxiety during the current outbreak of COVID-19 in immunocompromised and chronic disease patients in Saudi Arabia: A cross-sectional correlational study.

Coronavirus disease 2019 (COVID-19) infection has become a clinical threat to healthy people as well as immunocompromised patients and those with pre-existing chronic diseases around the world. This study, which used a cross-sectional correlational design, aimed to assess the levels of fear and health anxiety and to investigate their predictors during the current outbreak of COVID-19 in immunocompromised and chronic disease patients in Saudi Arabia. Sociodemographic and clinical data, fear of COVID-19, and health anxiety measurements were collected by online surveys from June 15 to July 15, 2020. Univariate and multiple linear regression analysis was used to identify predictors. A total of 1,030 patients in 13 provinces in Saudi Arabia completed the questionnaire. A significant number of patients with chronic diseases experienced considerable levels of fear and anxiety during the COVID-19 outbreak. It was found that 21.44% of participants met the criteria for anxiety cases, and 19.4% were considered borderline anxiety cases. In regression analysis, significant predictors of fear and health anxiety were female gender, lower education, middle-aged, divorced or widowed, receiving immunosuppressants, type of chronic disease (Crohn's disease, hypertension, and cardiovascular diseases), and media use as a source of knowledge about COVID-19. Immunocompromised and chronic disease patients are vulnerable to fear and anxiety during epidemic infectious diseases such as COVID-19. Optimizing this population's compliance with appropriate infection prevention and control strategies is crucial during the infectious outbreaks to ensure their safety, to decrease the risk of infection and serious complications, and reduce their fear and health anxiety. Effective positive psychological interventions and support strategies also need to be immediately implemented to increase psychological resilience and improve the mental health of these patients. Due to the COVID-19 outbreak, chronic disease patients in Saudi Arabia need special attention from health authorities, policymakers, and healthcare professionals to manage maladaptive forms of health anxiety and fear.

Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City.

BACKGROUND: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. METHODS: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. RESULTS: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age. The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07-3.01; P = 0.027) were independent predictors of in-hospital death after adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51-3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06-5.87; P = 0.049) were independent predictors of in-hospital death. CONCLUSION: Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.

Cardiovascular disease in patients with COVID-19: evidence from cardiovascular pathology to treatment.

The coronavirus disease-2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly developed into a global pneumonia pandemic. Cardiovascular disease is the major comorbidity of COVID-19 patients and is closely related to the severity of COVID-19. SARS-CoV-2 infection can directly or indirectly cause a series of cardiac complications, including acute myocardial injury and myocarditis, heart failure and cardiac arrest, arrhythmia, acute myocardial infarction, cardiogenic shock, Takotsubo cardiomyopathy, and coagulation abnormalities. Intensive research on the SARS-CoV-2-associated cardiovascular complications is urgently needed to elucidate its exact mechanism and to identify potential drug targets, which will help to formulate effective prevention and treatment strategies. Hence, this review will summarize recent progress regarding the effects of COVID-19 on the cardiovascular system and describe the underlying mechanism of cardiovascular injury caused by SARS-CoV-2.

Endothelial cells and SARS-CoV-2: An intimate relationship.

Angiotensin-converting enzyme 2 (ACE2) is an important player of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II into angiotensin (1-7). While expressed on the surface of human cells, such as lung, heart, kidney, neurons, and endothelial cells (EC), ACE2 is the entry receptor for SARS-CoV-2. Here, we would like to highlight that ACE2 is predominant on the EC membrane. Many of coronavirus disease 2019 (COVID-19) symptoms have been associated with the large recruitment of immune cells, directly affecting EC. Additionally, cytokines, hypoxia, and complement activation can trigger the activation of EC leading to the coagulation cascade. The EC dysfunction plus the inflammation due to SARS-CoV-2 infection may lead to abnormal coagulation, actively participating in thrombo-inflammatory processes resulting in vasculopathy and indicating poor prognosis in patients with COVID-19. Considering the intrinsic relationship between EC and the pathophysiology of SARS-CoV-2, EC-associated therapies such as anticoagulants, fibrinolytic drugs, immunomodulators, and molecular therapies have been proposed. In this review, we will discuss the role of EC in the lung inflammation and edema, in the disseminate coagulation process, ACE2 positive cancer patients, and current and future EC-associated therapies to treat COVID-19.

COVID-19 and cardiovascular diseases.

The coronavirus disease 2019 (COVID-19) remains a global public health emergency. Despite being caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), besides the lung, this infectious disease also has severe implications in the cardiovascular system. In this review, we summarize diverse clinical complications of the heart and vascular system, as well as the relevant high mortality, in COVID-19 patients. Systemic inflammation and angiotensin-converting enzyme 2-involved signaling networking in SARS-CoV-2 infection and the cardiovascular system may contribute to the manifestations of cardiovascular diseases. Therefore, integration of clinical observations and experimental findings can promote our understanding of the underlying mechanisms, which would aid in identifying and treating cardiovascular injury in patients with COVID-19 appropriately.

Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized With COVID-19: Findings From the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has exposed longstanding racial and ethnic inequities in health risks and outcomes in the United States. We aimed to identify racial and ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. METHODS: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7868 patients by race/ethnicity treated at 88 hospitals across the United States between January 17, 2020, and July 22, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events (death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization alone. Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. RESULTS: Among 7868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios for mortality were 0.93 (95% CI, 0.76-1.14) for Black patients, 0.90 (95% CI, 0.73-1.11) for Hispanic patients, and 1.31 (95% CI, 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median odds ratio across hospitals was 1.99 (95% CI, 1.74-2.48). Results were similar for major adverse cardiovascular events. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted odds ratio, 1.48 [95% CI, 1.16-1.90]). CONCLUSIONS: Although in-hospital mortality and major adverse cardiovascular events did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity because of their disproportionate representation among COVID-19 hospitalizations.

ACE2 mouse models: a toolbox for cardiovascular and pulmonary research.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.

Cardiac inflammation in COVID-19: Lessons from heart failure.

Cardiovascular disease (CVD) is the most common co-morbidity associated with COVID-19 and the fatality rate in COVID-19 patients with CVD is higher compared to other comorbidities, such as hypertension and diabetes. Preliminary data suggest that COVID-19 may also cause or worsen cardiac injury in infected patients through multiple mechanisms such as 'cytokine storm', endotheliosis, thrombosis, lymphocytopenia etc. Autopsies of COVID-19 patients reveal an infiltration of inflammatory mononuclear cells in the myocardium, confirming the role of the immune system in mediating cardiovascular damage in response to COVID-19 infection and also suggesting potential causal mechanisms for the development of new cardiac pathologies and/or exacerbation of underlying CVDs in infected patients. In this review, we discuss the potential underlying molecular mechanisms that drive COVID-19-mediated cardiac damage, as well as the short term and expected long-term cardiovascular ramifications of COVID-19 infection in patients.

Diabetes, obesity and COVID-19: A complex interplay.

With the accumulation of observational data showing an association of metabolic co-morbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions which arise from this relationship, and the types of studies needed to answer those questions. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience of or interest in the management of COVID-19.

A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization.

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.

Prevalence of co-morbidities and their association with mortality in patients with COVID-19: A systematic review and meta-analysis.

AIM: To estimate the prevalence of both cardiometabolic and other co-morbidities in patients with COVID-19, and to estimate the increased risk of severity of disease and mortality in people with co-morbidities. MATERIALS AND METHODS: Medline, Scopus and the World Health Organization website were searched for global research on COVID-19 conducted from January 2019 up to 23 April 2020. Study inclusion was restricted to English language publications, original articles that reported the prevalence of co-morbidities in individuals with COVID-19, and case series including more than 10 patients. Eighteen studies were selected for inclusion. Data were analysed using random effects meta-analysis models. RESULTS: Eighteen studies with a total of 14 558 individuals were identified. The pooled prevalence for co-morbidities in patients with COVID-19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension, 11.5% (9.7 to 13.4) for diabetes, and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD). For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease and cancer, the pooled prevalences were all less than 4%. With the exception of cerebrovascular disease, all the other co-morbidities presented a significantly increased risk for having severe COVID-19. In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease and cancer. CONCLUSIONS: In individuals with COVID-19, the presence of co-morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID-19 and mortality. These findings have important implications for public health with regard to risk stratification and future planning.

Long-term infection of SARS-CoV-2 changed the body's immune status.

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.

Role of Aging and the Immune Response to Respiratory Viral Infections: Potential Implications for COVID-19.

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.