Effect of COVID-19 on Endothelial Function
Condition: COVID-19; Endothelial Dysfunction
MeSH terms: COVID-19
Study type: Observational

Summary: 
      COVID-19 disease (coronavirus disease 2019) primarily affects the respiratory system, using
      the angiotensin-converting enzyme 2 receptor. However, there is increasing evidence that
      COVID-19 can also affect the heart (myocardial injury, myocarditis, arrhythmias) and the
      vascular system, effects that may worsen the clinical outcome of patients.

      The aim of this study is to assess the effect of COVID-19 on the patients' endothelial
      function, during the acute phase of the disease (inpatient), shortly after recovery (2
      months) and in the mid-term (6 months). Evaluation of endothelial function will be performed
      non-invasively by the method of Peripheral Arterial Tonometry (PAT) using the EndoPAT2000
      system (Itamar Medical, Israel).

      This is a prospective, case-controlled, single-center clinical observational study.

      The study will include adult patients who developed COVID-19 disease for whom admission for
      hospitalization was required, while the control group will consist of healthy volunteers
      matched for age, gender and cardiovascular risk factors.

      Patients enrolled in the study will undergo the following visits:

        -  Visit 1: Hospitalization

        -  Visit 2: 2 months after discharge

        -  Visit 3: 6 months after discharge

        -  Visit 4: 1 year after discharge Patients will be subjected to measurement of the
           reactive hyperemia index with the EndoPAT2000 system in Visits 1, 2 and 3.

      The aim of the study is to compare the endothelial function between the two groups (COVID-19
      vs. Controls).
    

Detailed description: 
      1. Introduction COVID-19 disease (coronavirus disease 2019) primarily affects the
           respiratory system, using the angiotensin-converting enzyme 2 receptor. However, there
           is increasing evidence that COVID-19 can also affect the heart (myocardial injury,
           myocarditis, arrhythmias) and the vascular system, effects that may worsen the clinical
           outcome of patients.

           Regarding COVID-19, there is increasing evidence of endothelial dysfunction, both
           directly due to direct infection of the vascular endothelium by the SARS-COV-2 virus
           (endothelitis), and indirectly due to the systemic inflammatory response and cascade of
           cytokines.

           In the context of this study, the evaluation of endothelial function will be performed
           non-invasively by the method of Peripheral Arterial Tonometry (PAT) using the
           EndoPAT2000 system (Itamar Medical, Israel). The EndoPAT system quantifies the
           endothelium-dependent pulsatile arterial volume changes. During the examination,
           plethysmography biosensors are placed in the right and left patient's index fingers.
           Subsequently, arterial tone is measured in three phases:

           A. at rest (baseline) B. during ischemia caused by a cuff inflated in one of the two
           arms at a level above that of systolic blood pressure for a period of 5 minutes C.
           during the phase of reactive hyperemia after the lifting of the arterial blockade by
           deflating the cuff The arterial tone signals detected in the above phases of the
           examination by the plethysmography biosensors are converted into digital signals for
           each upper limb and the EndoPAT2000 system software finally calculates the hyperemic
           vascular response (Ln Reactive Hyperemia Index-LnRHI). Endothelial dysfunction is
           defined as LnRHI≤0.51.

        2. Aim of the study The aim of this study is to assess the effect of COVID-19 on the
           patients' endothelial function, during the acute phase of the disease (inpatient),
           shortly after recovery (2 months) and in the mid-term (6 months).

        3. Methods This is a prospective, case-controlled, single-center clinical observational
           study.

      The study will include adult patients who developed COVID-19 disease for whom admission for
      hospitalization was required, while the control group will consist of healthy volunteers
      matched for age, gender and cardiovascular risk factors.

      Based on the limited existing data, patients in the COVID group are expected to have an
      average LnRHI of 0.58 (SD 0.25) at 2 months after discharge versus an average LnRHI of 0.79
      in the control group. By selecting α=0.05, power=90% and enrollment ratio=1, the inclusion of
      30 patients in each group is required to detect the above difference (60 in total).

      Patients enrolled in the study will undergo the following visits:

        -  Visit 1: Hospitalization

        -  Visit 2: 2 months after discharge

        -  Visit 3: 6 months after discharge

        -  Visit 4: 1 year after discharge Patients will be subjected to measurement of the
           reactive hyperemia index with the EndoPAT2000 system in Visits 1, 2 and 3.

      For all participants, the following will also be recorded:

        -  Demographics, cardiovascular risk factors, past medical history, chronic medical
           treatment

        -  Body weight, body mass index (BMI), systolic and diastolic blood pressure, resting heart
           rate

        -  Laboratory testing: Ht, Hgb, PLT, WBC, Ur, Cr, K, Na, SGOT, SGPT, UA, total cholesterol,
           LDL cholesterol, small dense LDL cholesterol, HDL cholesterol, triglycerides, non-HDL
           cholesterol, fasting glucose, HbA1c, insulin, hsCRP, thyroid function check (TSH, T3,
           fT4), hs Troponin I

        -  ECG

        -  Thansthoracic ultrasound study (LVEF, GLS, parameters of diastolic function)

        -  Thrombotic complications, cardiovascular events, hospitalizations
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study will include adult patients who developed COVID-19 disease for which admission
        for hospitalization was required, while the control group will be healthy matched
        volunteers for age, gender and cardiovascular risk factors.
      
Biospecimen description: 
      Whole blood