COVID-19 Blood Pressure Endothelium Interaction Study (OBELIX)

Study Overview
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Brief Summary
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The current COVID-19 pandemic (caused by the SARS-CoV-2 virus) represents the biggest medical challenge in decades. Whilst COVID-19 mainly affects the lungs it also affects multiple organ systems, including the cardiovascular system. There are documented associations between severity of disease and risk of death and To provide all the information required by review bodies and research information systems, we ask a number of specific questions. This section invites you to give an overview using language comprehensible to lay reviewers and members of the public. Please read the guidance notes for advice on this section. 5 DRAFT Full Set of Project Data IRAS Version 5.13 advancing age, male sex and associated comorbid disease (hypertension, ischaemic heart disease, diabetes, obesity, COPD and cancer). The most common complications include cardiac dysrhythmia, cardiac injury, myocarditis, heart failure, pulmonary embolism and disseminated intravascular coagulation. It is thought that the mechanism of action of the virus involves binding to a host transmembrane enzyme (angiotensin- converting enzyme 2 (ACE2)) to enter some lung, heart and immune cells and cause further damage. While ACE2 is essential for viral invasion, it is unclear if the use of the common antihypertensive drugs ACE inhibitors or angiotensin receptor blockers (ARBs) alter prognosis. This study aims to look closely at the health of the vascular system of patients after being treated in hospital for COVID-19 (confirmed by PCR test) and compare them to patients who had a hospital admission for suspected COVID-19 (negative PCR test) . Information from this study is essential so that clinicians treating patients with high blood pressure understand the impact of the condition and these hypertension medicines in the context of the current COVID-19 pandemic. This will allow doctors to effectively treat and offer advice to patients currently prescribed these medications or who are newly diagnosed with hypertension.

Detailed Description
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COVID-19 is pandemic and, though it primarily affects the lungs, there is evidence of cardiovascular system involvement. Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction. While ACE2 is essential for viral invasion, it is unclear if the use of the common antihypertensive drugs ACE inhibitors or angiotensin receptor blockers alter prognosis.

Official Title
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COVID-19 Blood Pressure Endothelium Interaction Study

Conditions
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COVID, Hypertension

Intervention / Treatment
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* Diagnostic Test: ABPM
* Diagnostic Test: ECG
* Diagnostic Test: FMD
* Diagnostic Test: PWV
* Diagnostic Test: Rarefaction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission between 01/04/2020 and 31/12/2020 Clinically suspected or PCR confirmed COVID-19 Age 30-60 years No history of hypertension or current drug treatment for hypertension Exclusion Criteria: Inability to give informed consent/lack of capacity Non-English speakers BMI >40 eGFR <60 ml/min Pregnancy History of Cancer within 5 years Persistent atrial fibrillation Severe illness, at investigator discretion Prescription of BP lowering drugs Corticosteroid (chronic use) Immunosupressive agents NSAIDs (chronic use)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID+ PCR<br>Subjects who are SARS-CoV-2 PCR+ve and/or have diagnostic CXR or CT chest features of COVID -19 | Diagnostic Test: ABPM<br>* 24 hour ambulatory blood pressure monitoring<br>Diagnostic Test: ECG<br>* Electrocardiogram<br>Diagnostic Test: FMD<br>* Flow mediated dilatation<br>Diagnostic Test: PWV<br>* Pulse wave velocity<br>Diagnostic Test: Rarefaction<br>* nailbed capillaroscopy<br>|
| COVID- PCR<br>subjects admitted with COVID-19 like symptoms but are SARS-CoV-2 PCR-ve and have CXR or CT chest that show low probability of COVID-19 will form the control group | Diagnostic Test: ABPM<br>* 24 hour ambulatory blood pressure monitoring<br>Diagnostic Test: ECG<br>* Electrocardiogram<br>Diagnostic Test: FMD<br>* Flow mediated dilatation<br>Diagnostic Test: PWV<br>* Pulse wave velocity<br>Diagnostic Test: Rarefaction<br>* nailbed capillaroscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ABPM systolic blood pressure | Ambulatory Blood Pressure Monitoring systolic blood pressure | 24 hours (all day and night) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hr ABPM DBP | Ambulatory Blood Pressure Monitoring diastolic blood pressure | 24 hours (all day and night) | 
| day ABPM SBP | Day Ambulatory Blood Pressure Monitoring systolic blood pressure | 8am to 8pm | 
| day ABPM DBP | Day Ambulatory Blood Pressure Monitoring diastolic blood pressure | 8am to 8pm | 
| night ABPM SBP | Night Ambulatory Blood Pressure Monitoring systolic blood pressure | 8pm to 8am | 
| night ABPM DBP | Night Ambulatory Blood Pressure Monitoring diastolic blood pressure | 8pm to 8am | 
| dipping status | The fall in pressure, called the dip, is defined as the difference between daytime mean systolic pressure and nighttime mean systolic pressure expressed as a percentage of the day value | 24 hours (all day and night) | 
| morning surge | he morning surge was defined as the difference between the mean systolic blood pressure during the 2 hours after waking and arising minus the mean systolic blood pressure during the hour that included the lowest blood pressure during sleep. | 24 hours (all day and night) | 
| 24 hour ABPM HR | 24 hour Ambulatory Blood Pressure Monitoring heart rate | 24hr (all day and night) | 
| day ABPM HR | Day Ambulatory Blood Pressure Monitoring heart rate | 8 am to 8 pm | 
| night ABPM HR | Night Ambulatory Blood Pressure Monitoring heart rate | 8pm to 8 am | 
| Immune phenotyping | Immune phenotyping includes cellular and humoral markers of immune cell activation and senescence within populations of key leukocyte subsets e.g. lymphocytes and monocytes | at baseline | 
| Microparticle assessments | microparticles are being assessed as biomarkers and biovectors of vascular damage and endothelial dysfunction | at baseline |