NO-mediated Vascular Function in Covid-19 Patient
Condition: COVID-19 Pneumonia
MeSH terms: COVID-19
Study type: Observational [Patient Registry]

Summary: 
      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.
    

Detailed description: 
      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).
    

Intervention name(s): Single passive leg movement
Intervention type(s): Diagnostic Test
Intervention description(s): The investigation consists of a non-invasive evaluation by ultrasounds performed on the common femoral artery investigating the speed of arterial blood flow [Leg Blood Flow LBF] and diameter of vessel with a dedicated ultrasound system (General Electric Medical Systems, Milwaukee, WI) using Doppler method, before and after a passive flexion-extension movement of the knee. A linear probe will be used with a frequency of 5 MHz. Using the diameter of the artery and the average volume (Vmean), the LBF will be calculated every second with the formula=Average volume*PiGreco*(vessel diameter / 2)2*60.
The subject will be placed in a sitting position for 20 minutes before the test. The protocol consists of image acquisition for 60 seconds (basal measurement), followed by a passive flexion-extension of the knee (single passive leg movement). The knee flexion will be performed by health care personnel at a rate of 1 Hz. At the end of the movement, the recording will continue for 60 seconds.
Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients, from acute care hospitals, diagnosed with COVID-19 pneumonia, with documented
        positive throat swab, within one month from discharge.
      
Keywords: COVID -19; Vascular function; Endothelial function