Pro-thrombotic Status in Patients With SARS-Cov-2 Infection

Study Overview
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Brief Summary
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The present study is ideated to prospectively investigate in patients with severe acute respiratory syndrome (SARS) due to Coronavirus 19 (SARS-Cov-2) infection and moderate-severe respiratory failure the patterns and changes in platelet reactivity, thrombotic status and endothelial function. The observed patterns and changes will be related with inflammatory status, myocardial injury and outcomes

Detailed Description
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Preliminary evidences suggested that patients with SARS-Cov-2 infection and concomitant presence of cardiovascular risk factors (i.e. arterial hypertension) and/or cardiovascular history (i.e. prior myocardial infarction) are at poor prognosis. The first reports from China suggested in patients with SARS-Cov-2 infection a heightened inflammatory burden associated with significant changes in coagulative status (i.e. low platelet count, increased D-dimer) and dysfunction of micro-vessels in pulmonary circulation. No data are available about patterns and changes in platelet reactivity, activation of coagulation factors and endothelial function during SARS-Cov-2 infection. The present study is ideated to fill this gap. Patients with moderate to severe respiratory failure due to SARS-Cov-2 infection will be enrolled. One blood sample will be obtained from each patient at the early, mid and late stage of disease. Several markers of platelet, coagulation and endothelial function will be related with laboratory, clinical, electrocardiographic, imaging (transthoracic echocardiogram, pulmonary ultrasonography, computed tomography) and outcome data. To better describe typical patterns of disease regarding inflammation, platelet function and coagulation alteration, data from cases will be compared with control groups negative for SARS-CoV-2 infection, but with ST-segment elevation myocardial infarction or moderate-severe respiratory failure due to other agents.

Official Title
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Patterns and Changes in Platelet Reactivity, Thrombotic Status and Endothelial Function in Hospitalized Patients With SARS-Cov-2 Infection

Conditions
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Severe Acute Respiratory Syndrome Coronavirus 2

Intervention / Treatment
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* Other: SARS-Cov-2 infection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of moderate-severe respiratory failure (PaO2/FiO2 <200) Diagnosis of SARS-CoV-2 infection + one of the following invasive mechanical ventilation (cohort A) non invasive mechanical ventilation (cohort B) only oxygen support Exclusion Criteria: Previous chronic use of P2Y12 inhibitors Need for chronic oral anti-coagulation therapy Know disorder of coagulation or platelet function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: SARS-Cov-2 infection<br>Single study group of patients with respiratory failure due to SARS-Cov-2 infection. Three blood samples will be collected at different stages of disease: early, defined as first 96 hours, mid, defined as time from 96 hours and 14 days, late. defined as >14 days | Other: SARS-Cov-2 infection<br>* blood sample withdrawal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| on-treatment platelet reactivity | patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli | early stage of disease (first 96 hours) | 
| on-treatment platelet reactivity | patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli | mid stage of disease (96 hours - 14 days) | 
| on-treatment platelet reactivity | patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli | late stage of disease (>14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| apoptosis rate in human umbilical vein endothelial cells (HUVEC) | patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study. | early stage of disease (first 96 hours) | 
| apoptosis rate in human umbilical vein endothelial cells (HUVEC) | patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study. | mid stage of disease (96 hours - 14 days) | 
| Nitric oxide (NO) intracellular levels | patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study. | late stage of disease (>14 days) | 
| Nitric oxide (NO) intracellular levels | patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study. | early stage of disease (first 96 hours) | 
| Nitric oxide (NO) intracellular levels | patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study. | mid stage of disease (96 hours - 14 days) | 
| reactive oxygen species (ROS) levels | patterns and changes of ROS | early stage of disease (first 96 hours) | 
| reactive oxygen species (ROS) levels | patterns and changes of ROS | mid stage of disease (96 hours - 14 days) | 
| reactive oxygen species (ROS) levels | patterns and changes of ROS | late stage of disease (>14 days) | 
| coagulation factors levels | patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL) | early stage of disease (first 96 hours) | 
| coagulation factors levels | patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL) | mid stage of disease (96 hours - 14 days) | 
| coagulation factors levels | patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL) | late stage of disease (>14 days) | 
| respiratory function | values of FEV1% as assessed by spirometry | 6-month | 
| respiratory function | values of FEV1% as assessed by spirometry | 12-month | 
| cardiac function | values of left ventricular ejection fraction as assessed by transthoracic echocardiogram | 6-month | 
| cardiac function | values of left ventricular ejection fraction as assessed by transthoracic echocardiogram | 12-month | 
| clinical outcome | occurrence of death, myocardial infarction, stroke and other major adverse events | 12-month |