NO-mediated Vascular Function in Covid-19 Patient

The 2019 coronavirus-induced infection (COVID-19) has caused a pandemic that has spread worldwide. Up to date, many subjects affected by the virus report important sequelae on different organs increasing morbidity and exacerbating previous pathological conditions. Mortality is also increased in cases of comorbidities such as cardiovascular disease, hypertension and diabetes. COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). Concerning the specific interaction of SARS-CoV-2 with the cardiovascular system, we know that this virus enters the body through the receptors for the conversion of angiotensin II (ACE2r) that are present in the lungs, heart, intestinal epithelium and vascular endothelium. This receptor's availability suggests a multi-organ involvement with a consequent multi-organ dysfunction, as found in patients affected by SARS-CoV-2 infection.

Furthermore, poor vascular peripheral function -usually correlated with old age and long periods of bed rest or hypomobility- is a distinguishing characteristic of the population affected by COVID-19, as well. Thus, it is reasonable to expect that peripheral vascular function, already deteriorated by aging and common age-related diseases, can be further compromised by COVID-19 and by the forced hypomobility, typically experienced during the acute phase of the disease.

The main aim of this project will be to investigate the peripheral NO-mediated vascular function in the leg of patients recovering from Covid-19 pneumonia.

A significant vascular dysfunction is expected to be found in post COVID individuals and to be correlated to the relevant clinical variables.

The 2019 coronavirus-induced infection (COVID-19) has caused a pandemic that has spread worldwide, causing approximately 250,000 deaths to date. Even if the contagion curves seem to stabilize, many subjects have been affected by the virus and report important sequelae on the cardiovascular system. This can be explained by the assumption that COVID-19 interacts with the cardiovascular system at different levels, increasing morbidity and exacerbating previous pathological conditions. Mortality is, in fact, increased in cases of comorbidities such as cardiovascular disease, hypertension and diabetes.

COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). This virus enters the body through the receptor for the conversion of angiotensin \[angiotensin-converting enzyme 2, ACE2\]. This receptor is present in the lungs, heart, intestinal epithelium and vascular endothelium. The receptor's availability suggests a multi-organ dysfunction, as found in patients affected by SARS-CoV-2 infection. In particular, the infection of endothelial cells or pericytes, as well as the cytokine-mediated inflammatory cascade induced by the infection, can lead to severe microvascular and macrovascular dysfunctions.

It is important to underline that endothelial damage is one of the precursors of the atherosclerosis and endothelial dysfunction is related to pulmonary, cardiac and neurological diseases. Furthermore, poor vascular function is related to old age and long periods of bed rest or hypomobility, those characteristics are present in the population affected by COVID-19, as well. Thus, it is reasonable to expect that peripheral vascular function, already deteriorated by aging and common age-related diseases, can be further compromised by COVID-19 and by the forced hypomobility typically experienced during the acute phase of the disease.

Recently, the endothelial function mediated by nitric oxide (NO) has been easily and non-invasively investigated on common femoral artery with the ultrasound technique of Single Passive Leg Movement. The main aim of this project will be to investigate the NO-mediated vascular function in patients recovering from Covid-19 pneumonia, within one month from discharge in order to verify the presence of endothelial dysfunction acutely induced by the viral infection.

The secondary aim will be to evaluate the correlation between NO-mediated vascular function (evaluated by ultrasound technique) and age, anthropometric parameters (height, weight, Body Mass Index), clinical parameters, oxygenation status, physical performance and pharmacology.

The data will be analysed with the Shapiro-Wilk test to evaluate their "normality" and will be presented as mean ± standard deviation (sd) or median (interquartile range) depending on the type of distribution detected. Correlation tests (Pearson/Spearman) between ultrasound evaluation on peripheral blood flow and vessels and oxygenation levels, clinical, anthropometric and physical performance measures will then be performed. Values of p \<0.05 will be considered significant.

A significant peripheral vascular dysfunction is expected to be found in post COVID individuals and to be correlated to relevant clinical variables (i.e. muscle strength, respiratory parameters, oxygenation status).

Eligibility Criteria:
Inclusion criteria:

* Diagnosis of COVID-19 pneumonia
* Clinical stability condition (temperature \<37.5 ° C, Respiratory Rate (RR) \<22 breaths/min, Heart Rate (HR)\> 50 beats/minute and \<120 beats/minute, absence of major arrhythmias, hemodynamic stability)
* Possibility to reach the sitting position independently

Exclusion criteria:

-Previous cardiovascular, respiratory, neurological or orthopaedic diseases.