The COVID-19 pandemic is the biggest medical challenge in decades. Individuals with pre-existing cardiovascular diseases have a higher risk of severe disease and death from COVID-19. The SARS-CoV-2 virus causes infection by targeting a molecule on the walls of the cells lining the lungs and the blood vessels leading to injury. There are concerns that after recovery from COVID-19, the damage sustained by these cells may have long-term consequences including high blood pressure, stroke and heart attacks. The burden of high blood pressure as a result of the pandemic is unknown and a greater understanding of COVID-19 impact on blood pressure and its underlying mechanisms is urgently needed.

LOCHINVAR is based on our pilot study "COVID-19 blood pressure endothelium interaction study" (OBELIX,NCT04409847, IRAS 284453), which found that patients with normal blood pressure at the time of hospital admission with COVID-19 showed a nine-point higher blood pressure ≥12 weeks after recovery, compared to a group without COVID-19. LOCHINVAR will extend the OBELIX study aiming to establish if COVID-19 increases the risk of developing high blood pressure and investigating underlying mechanisms through detailed measurements of blood pressure, blood vessel function, hormones and chemicals in the blood, urine and stool.

The investigators will invite 150 adults without pre-existing high blood pressure who were discharged from hospital after an admission: half with COVID-19 and half without. Baseline visit will be ≥12 weeks after discharge for measurements of blood pressure, tests of heart and blood vessel health, blood, urine and stool samples along with questionnaires on mood and quality of life. Two further study visits follow, at 12 and 18 months.

This study will generate crucial evidence on the long-term impact of COVID-19 on blood pressure along with information on potential mechanisms of this effect with immediate, transferable impact on clinical practice and inform risk mitigation measures.

The Coronavirus Disease-19 (COVID-19) pandemic is one of the biggest medical challenges in recent years. Whilst COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome, it also affects multiple organ systems, including the cardiovascular system(1-3). There are documented associations between severity of disease/mortality risk and advancing age, male sex and associated comorbid disease (hypertension, ischaemic heart disease, diabetes, obesity, COPD and cancer).(4,5) The most common complications include cardiac dysrhythmia(6,7), cardiac injury(8,9), myocarditis, heart failure, pulmonary embolism10 and disseminated intravascular coagulation(11).

The SARS-CoV-2 virus uses the ACE2 receptor (ACE2) to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.(12) This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction.(12) In addition, ACE2 is expressed in several other organs including cells lining the blood vessels (endothelial cells), ACE2 is a key player in the renin-angiotensin system (RAS) which is important in blood pressure regulation and is a target for some of the commonly used drugs used in the treatment of blood pressure. 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 in those with COVID-19 infection.(12) Furthermore, there is evidence that the normally occurring bacteria in the gut (gut microbiome) directly influences the makeup of the human immune system and has been implicated in severity of COVID-19 as well as in the magnitude of the immune system response to SARS-CoV-2 infection(13).

This study (LOCHINVAR) is based on the pilot study "COVID-19 blood pressure endothelium interaction study" (OBELIX), funded by the Chief Scientific Office. Preliminary results showed that participants who had COVID-19 infection had an 8.6mmHg increase in their average 24hr systolic blood pressure, compared to those that did not have COVID-19 infection. The investigators will increase our recruitment of potential participants to meet our sample size of 150 participants (75 SARS-CoV-2 +ve cases and 75 SARS-CoV-2 -ve cases) built on OBELIX. This study will allow us to have a better understanding of the risks of developing high blood pressure or uncontrolled blood pressure following COVID-19 infection. This will allow doctors to be able to make a recommendation on the current/long term management of people with high blood pressure beyond the pandemic.

Inclusion Criteria:

• Age 30-60 years
• Admission between 01/09/2020 - 31/12/2021
• Clinically suspected or Confirmed COVID-19 Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test confirmed COVID-19 on admission
• No history of hypertension or current drug treatment for hypertension

Controls

1. Age 30-60
2. No history of hypertension
3. No antihypertensive drugs
4. Confirmed RT-PCR test negative and admission through Queen Elizabeth University Hospital immediate assessment unit and acute receiving units 01/09/2020 to 31/12/2021 or no history of SARS-CoV-2 infection or COVID-19

Exclusion Criteria:

Inability to give informed consent/lack of capacity 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
• Oral Corticosteroid (chronic use)
• Immunosuppressive agents
• Oral NSAIDs (chronic use)

Patients admitted through Queen Elizabeth University Hospital (QEUH) receiving units with suspected/confirmed COVID-19 during 01/09/2020-31/12/2021 and who are alive at discharge. Clinically suspected COVID-19 should have either fever, new onset cough and/or anosmia/dysgeusia and/or ≥2 of the following presenting features (fatigue/generalised weakness, headache, myalgia, sore throat/coryzal symptoms, breathlessness, anorexia/nausea/vomiting, diarrhoea, contact with known COVID-19 positive case). OBELIX participants who have given consent previously will be re-contacted.