Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19).

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12-15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

COVID-19 in patients with cardiac disease: Impact and variables associated with mortality in a cardiology center in Brazil.

BACKGROUND: Cardiovascular disease is associated with severe COVID-19. Our aim was to describe clinical and laboratory features (including electrocardiographic and echocardiographic ones) and outcomes of patients with cardiac disease hospitalized with COVID-19. METHODS: This is an observational retrospective study of consecutive adult patients admitted, between March and September of 2020, with confirmed SARSCoV-2 infection. Data were collected as per the ISARIC case report form and complemented with variables related to heart disease. RESULTS: One hundred twenty-one patients were included. Mean age was 60 SD 15.2 years and 80/121(66.1%) were male. Two-thirds of the patients (80/121, 66.1%) had COVID-19 at the time of hospital admission and COVID-19 was the reason for hospitalization in 42 (34.7%). Other reasons for hospital admission were acute coronary syndrome (26%) and decompensated heart failure (14.8%). Chronic cardiac diseases were found in 106/121 (87.6%), mostly coronary artery disease (62%) or valve disease (33.9%). A transthoracic echocardiogram was performed in 93/121(76.8%) and enlarged cardiac chambers were found in 71% (66/93); admission ECG was done in 93 cases (93/121, 76.8%), and 89.2% (83/93) were abnormal. Hospital-acquisition of COVID-19 occurred in 20 (16.5%) of patients and their mortality was 50%. On bivariate analysis for mortality, BNP levels and troponin levels were NOT associated with mortality. On multivariate analysis, only C reactive protein levels and creatinine levels were significant. CONCLUSIONS: COVID-19 impacted the profile of hospital admissions in cardiac patients. BNP and troponin levels were not associated with mortality and may not be good prognostic discriminators in cardiac patients.

Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity.

The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic - obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipokines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients.

Systemic microvascular endothelial dysfunction and disease severity in COVID-19 patients: Evaluation by laser Doppler perfusion monitoring and cytokine/chemokine analysis.

BACKGROUND: Microvascular dysfunction, serum cytokines and chemokines may play important roles in pathophysiology of coronavirus disease 2019 (COVID-19), especially in severe cases. METHODS: Patients with COVID-19 underwent non-invasive evaluation of systemic endothelium-dependent microvascular reactivity - using laser Doppler perfusion monitoring in the skin of the forearm - coupled to local thermal hyperemia. Maximal microvascular vasodilatation (44 °C thermal plateau phase) was used as endpoint. A multiplex biometric immunoassay was used to assess a panel of 48 serum cytokines and chemokines. Severe COVID-19 (S-COVID) was defined according to WHO criteria, while all other cases of COVID-19 were considered mild to moderate (M-COVID). A group of healthy individuals who tested negative for SARS-CoV-2 served as a control group and was also evaluated with LDPM. RESULTS: Thirty-two patients with COVID-19 (25% S-COVID) and 14 controls were included. Basal microvascular flow was similar between M-COVID and controls (P = 0.69) but was higher in S-COVID than in controls (P = 0.005) and M-COVID patients (P = 0.01). The peak microvascular vasodilator response was markedly decreased in both patient groups (M-COVID, P = 0.001; S-COVID, P < 0.0001) compared to the healthy group. The percent increases in microvascular flow were markedly reduced in both patient groups (M-COVID, P < 0.0001; S-COVID, P < 0.0001) compared to controls. Patients with S-COVID had markedly higher concentrations of dissimilar proinflammatory cytokines and chemokines, compared to patients with M-COVID. CONCLUSIONS: In patients with COVID-19, especially with S-COVID, endothelium-dependent microvascular vasodilator responses are reduced, while serum cytokines and chemokines involved in the regulation of vascular function and inflammation are increased.

Systemic microvascular dysfunction in COVID-19.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while having lung injury as its most prominent feature, has been increasingly shown to affect endothelial cell function and the microvasculature. In this report, a woman with COVID-19, cardiac valve disease and spherocytosis was assessed with laser Doppler perfusion monitoring. Systemic microvascular reactivity was impaired during a worsening phase of COVID-19, but improved after clinical recovery; microcirculatory dysfunction paralleled systemic inflammation and pulmonary involvement. The assessment of systemic microcirculatory function may therefore provide insights on COVID-19 pathophysiology.

COVID-19 and Microvascular Disease: Pathophysiology of SARS-CoV-2 Infection With Focus on the Renin-Angiotensin System.

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.

Acute cardiac injury in patients with COVID-19.

INTRODUCTION: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. METHODS: A systematic review with a meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independent reviewers evaluated the selected manuscripts for the outcome "myocardial injury", defined by troponin elevation above the 99th percentile. The study heterogeneity and risk of bias were evaluated. RESULTS: Eight studies, with a total of 1,229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9%-27%). The heterogeneity among the studies was high (93%). CONCLUSIONS: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% according to current studies. Continuous research is needed to update these findings as the pandemic evolves and to define the implications of myocardial injury in the context of this infection.

Importance of the evaluation of systemic microvascular flow and reactivity in critically ill patients with coronavirus disease 2019 - COVID-19.

Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have, in fact, emerged as risk factors for a complicated evolution of COVID-19. Older age, cardiovascular disease including hypertension, diabetes and pulmonary disease, have been associated with more severe presentations and/or adverse prognosis. In this letter to the editor, we propose that the link between cardiovascular and metabolic diseases and the higher incidence and worse prognosis of COVID-19 patients is the (micro) vascular endothelium.

Systemic endothelial dysfunction: a common pathway for COVID-19, cardiovascular and metabolic diseases

Some of the mechanisms and conditions underlying endothelial dysfunction.A-human skin capillaries, visualized with high-resolution intravital color microscopy in the finger of a patient with obesity, metabolic syndrome and coronary artery disease.B- healthy control. The reduced number of capillaries can be noticed in A compared to B.Image 1.