Endothelial function, arterial stiffness and heart rate variability of patients with cardiovascular diseases hospitalized due to COVID-19.

BACKGROUND: The novel coronavirus disease (COVID-19) may cause vascular (e.g., endothelial dysfunction, and arterial stiffness), cardiac, autonomic (e.g., heart rate variability [HRV]), and systemic inflammatory response via direct viral attack, hypoxia-induced injury, or immunological dysregulation, especially in those patients with pre-existing cardiovascular diseases (CVD). However, to date, no study has shown prevalence of endothelial dysfunction, arterial stiffness and heart rate variability assessed by bedside peripheral arterial tonometry in patients with previous CVD hospitalized in the acute phase of COVID-19. OBJECTIVE: This study aimed to assess the prevalence of endothelial dysfunction, arterial stiffness, and altered HRV in patients with CVD hospitalized due to COVID-19. METHODS: This cross-sectional study was conducted from July 2020 to February 2021. Included male and female adult patients aged 40 to 60 years with previous CVD and diagnosed with COVID-19. Anthropometric data, comorbidities, and blood tests were analyzed. Endothelial function, arterial stiffness, and HRV were assessed using peripheral arterial tonometry (PAT), and the statistical significance was set at 5%. RESULTS: Fourteen (51.8%) patients presented endothelial dysfunction (reactive hyperemia index = 1.2 ± 0.3) and enhancement in the high-frequency component of HRV (p < 0.05). There was a high prevalence of endothelial dysfunction, especially in patients with chronic heart failure (10 (71.4%)). Patients with preserved endothelial function showed a high augmentation index normalized to a heart rate of 75 bpm (p < 0.01), suggesting arterial stiffness. CONCLUSION: Patients with CVD hospitalized due to COVID-19 presented endothelial dysfunction assessed using PAT, which could be used as a biomarker for arterial stiffness and altered HRV. The possibility of detecting vascular and autonomic changes during phase II of COVID-19 may help to prevent possible long-term complications.

Ultrasound findings in severe COVID-19: a deeper look through the carotid arteries.

Objective: To investigate vascular and perivascular abnormalities in the carotid arteries using ultrasound, as well as to evaluate their association with mortality and clinical variables in hospitalized patients with coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study in which 53 hospitalized patients with severe COVID-19 were evaluated and underwent carotid ultrasound. We documented the carotid ultrasound findings in these patients. Clinical, demographic, laboratory, and imaging features were analyzed and compared by statistical analysis to detect correlations between them. Results: Carotid ultrasound demonstrated luminal surface irregularity in 29 patients (55%), carotid plaques in 30 (57%), perivascular infiltration in four (8%), and increased intima-media thickness (IMT) in 31 (58%). Of the 31 patients with increased IMT, 19 (61%) died, and the association between increased IMT and COVID-19-related mortality was significant (p = 0.03). Logistic regression showed that the risk of death was 85% in patients who had increased IMT in combination with acute kidney injury at admission or a history of chronic kidney disease (p < 0.05). Conclusion: In hospitalized patients with severe COVID-19, carotid ultrasound can show increased IMT, luminal surface irregularity, carotid plaques, and perivascular infiltrates. The combination of increased IMT and kidney damage appears to increase the risk of death in such patients.

Objetivo: Investigar anormalidades vasculares e perivasculares nas artérias carótidas por meio de ultrassonografia e avaliar sua associação com mortalidade e variáveis clínicas em pacientes hospitalizados com COVID-19. Materiais e Métodos: Neste estudo prospectivo, 53 pacientes hospitalizados com COVID-19 grave foram avaliados e submetidos a ultrassonografia de carótida. Descrevemos os achados ultrassonográficos de carótida nesses pacientes. As correlações de características clínicas, demográficas, laboratoriais e de imagem foram analisadas e comparadas por meio de análise estatística. Resultados: A ultrassonografia carotídea demonstrou irregularidade da superfície luminal em 29 pacientes (55%), placas carotídeas em 30 pacientes (57%), infiltração perivascular em quatro pacientes (7,5%) e aumento da espessura médio-intimal (EMI) em 31 pacientes (58%). Dos pacientes com EMI aumentada, 19 (61%) morreram, com associação observada entre EMI aumentada e mortalidade por COVID-19 (p = 0,03). Um modelo de regressão logística mostrou que a probabilidade de óbito foi de 85% em pacientes com EMI aumentada e história de nefropatia crônica ou lesão renal aguda na internação (p < 0,05). Conclusão: Aumento da EMI, irregularidade da superfície luminal, placas carotídeas e infiltrados perivasculares foram encontrados na ultrassonografia carotídea em pacientes hospitalizados com COVID-19 grave. O aumento da EMI associado a danos nos rins pode aumentar o risco de morte.

Severe COVID-19: understanding the role of immunity, endothelium, and coagulation in clinical practice.

SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis.

Mapping COVID-19 functional sequelae: the perspective of nuclear medicine.

Severe acute respiratory syndrome coronavirus 2 infection is capable of affecting several organs. Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage. The impairment of four organs stands out among severe patients: lung, heart, kidney, and endothelium. The nuclear medicine field holds accurate and safe exam techniques, such as positron emission tomography-computed tomography and scintigraphy, that allow the anatomophysiological study of the majority of human organ systems. By choosing the most appropriate method and radiopharmaceutical, analyzing the presence of inflammation, fibrosis, changes in perfusion, and function of desired organs is possible. Therefore, its use in the monitoring of patients with coronavirus disease 2019 becomes relevant, especially for monitoring sequelae. In this review, we discuss the use of Nuclear Medicine in the detection, monitoring, and therapeutic evaluation of pulmonary and extrapulmonary sequelae by coronavirus disease 2019.

COVID-19 and obesity: the meeting of two pandemics.

COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

The severe form of COVID-19 is marked by an abnormal and exacerbated immunological host response favoring to a poor outcome in a significant number of patients, especially those with obesity, diabetes, hypertension, and atherosclerosis. The chronic inflammatory process found in these cardiometabolic comorbidities is marked by the overexpression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumoral necrosis factor-alpha (TNF-α), which are products of the Toll-Like receptors 4 (TLR4) pathway. The SARS-CoV-2 initially infects cells in the upper respiratory tract and, in some patients, spread very quickly, needing respiratory support and systemically, causing collateral damage in tissues. We hypothesize that this happens because the SARS-CoV-2 spike protein interacts strongly with TLR4, causing an intensely exacerbated immune response in the host's lungs, culminating with the cytokine storm, accumulating secretions and hindering blood oxygenation, along with the immune system attacks the body, leading to multiple organ failure.