HEART AND BLOOD PRESSURE EFFECTS BY COVID-19

EFFECTS OF COVID-19 ON CARDIOVASCULAR SYSTEM

Fig-1

The COVID-19 is having complex interactions with the cardiovascular system and other systems apart from the respiratory system.
We all know that pneumonia is the primary manifestation of the COVID-19 disease.

But in the on-time course, the disease spreads its wings to various body systems including the heart and blood system.

In the world, about 80% of the hospitalized COVID19 patients, are all with severe cardiovascular defects.

Of these figures, 40% are with high blood pressure,36% are with obesity,12% with other CVDs, and the remaining percentage with diabetes. All of them need intensive care.
20 to 40% of hospitalized cardiac patients are with chest pain, heart failure, arrhythmias (irregular heartbeats), and heart attacks.
Male elderly,immuno-deficient, and middle-aged people are the prime targets of the disease.

People below 50 years of age who do not have any pre-existing comorbidities may have mild to moderate pneumonia along with some mild respiratory symptoms and may get recover soon.

People who are above sixty years of age with weak immunity if infected with COVID-19 are at high risk of falling into cardiovascular diseases, including high Blood Pressure, diabetes, kidney damage, and neuronal complications even if they do not have any past history of them.

This is due to the complex interactions of the virus with the Renin-Angiotensin-Aldosterone-System. That is due to its affinity to the ACE2 receptor expressed in the cells of various systems of the body.

THE RAAAS (RENIN ANGIOTENSIN ALDOSTERONE ADH SYSTEM)

Fig-2

This system can also be called a RAS system as Angiotensin-II can represent both Aldosterone and ADH. See Fig-2 above.

Angiotensinogen is a peptide released by the liver in the bloodstream in response to a change in Blood Pressure or electrolytes.

Renin is an enzyme released by the kidneys in response to the liver secretion of the angiotensinogen.

Kidneys play an important role in regulating Blood Pressure.

Kidney releases renin whenever there is a fall in arterial pressure, blood sodium, and water level.

Renin converts angiotensinogen into angiotensin I, which is, in turn, converted to its active form angiotensin-II by ACE-1(Angiotensin Converting Enzyme-1).

Angiotensin-II acts on its receptor ATR-1(Angiotensin Receptor-1) situated in the pulmonary system and thereby increases the Blood Pressure in various ways as follows:-

1.By vasoconstriction. (Constriction of the blood vessels)

2.By stimulating the release of aldosterone, from the adrenal cortex.

Aldosterone helps kidneys to reabsorb sodium along with water by the loss of potassium at the distal tubule (DCT) of the nephron.

3.By stimulating the release of vasopressin, the Anti-Diuretic Hormone (ADH) from the posterior pituitary gland in the brain. This hormone acts on the collecting tubule of the nephron and helps it to reabsorb water alone back into the blood.

Thus the Renin-Angiotensin-Aldosterone-ADH-System (RAAAS) raises the blood pressure to normal in a healthy situation.

This RAAAS is controlled by another system that works in the opposite direction to nullify the RAAAS effects.

That system involves ACE-2-ATR-2-Angio(1-7)-Angio(1-9) We can simply form abbreviation for this as AAAA.

Therefore RAAAS means-Hypertension (High Blood Pressure), a rise in the secretions of inflammatory mediators such as cytokines, creatine kinase, clotting factors like d-dimer, lymphocytopenia, increase in sodium level, and decrease in potassium level.

On the contrary, AAAA means -Hypotension (Low Blood Pressure), suppression of the inflammatory mediators, a rise in potassium level, and a fall in sodium level.

Hence both the system should work equally in a balanced condition to keep us healthy.

If one system becomes overpowered on the other then our whole-body system will be in jeopardy.

Now one could easily understand how COVID-19 has detrimental effects on these systems.

In the coronavirus family, 2 alpha coronaviruses,229E, NL63, and 2 beta coronaviruses OC43, HKU1 are all harmless and they act on sialic acid (SA)receptors which are mostly present in the nasal pathways (URT)

The three harmful coronaviruses all belong to the family beta coronaviridae are SARS, MERS, and SARS2(COVID-19) use angiotensin-converting enzyme-2(SARS, SARS2), dipeptidyl peptidase-4(MERS) receptors for their cell entry. These receptors are primarily expressed in the LRT, which is from throat to lungs area.

In the lungs, ACE2 is predominantly expressed in the type-1 and type-2 pneumocytes, and the endothelial layer cells of the heart, the blood vessels, lymphatic vessels, and in the digestive, brain systems of our body.

COVID-19 gets easy entry into our body mostly through the nasal breathing followed by mouth breathing.

Once it entered first it affects the respiratory system followed by the heart-blood(cardio-vascular-CV) system, followed by the nervous (Brain) system and followed by the digestive system.

In this article, we are going to see in brief how it affects C.V.S (Heart and blood System).

See the above figure which illustrates the complete RAAA and AAAA systems of how they balance each other.

Coronavirus disturbs this balance by acting on and consuming the cell-bound ACE2 receptors. As a result, there is a depletion of the ACE2 receptor and thereby the RAAAS overpower the opponent system to rise the Blood Pressure and other inflammatory secretions to a dangerous level.

But still the available angiotensin-II may act on ATR2 and thereby tend to decrease the Blood Pressure by a blood vessel dilatory effect but that may not be strong enough.

As the virus damaged the ACE2 receptors there will be a cytokine storm that may cause inflammations and thick mucus in the lungs which results in difficulty in breathing, pneumonia, and hypoxia.

Hypoxia causes many cardiovascular problems including atrial fibrillations, ventricular tachyarrhythmia, and fibrillations.

The uncontrolled B.P may cause difficulty in cardiac output (afterload) which may lead to cardiac failure.

An uncontrolled potassium loss occurs through the kidney that leads to hypokalemia.

Hypokalemia may cause many cardiac problems including cardiac arrhythmias, atrial ventricular fibrillation, and finally heat attack.

Myocardial injuries are caused by the viral attack on the cardiac myocytes in which there are well-differentiated endothelial cells with high expression of ACE2 receptors.

A rise in d-dimer a fibrin degradation product can cause blood clot formations such as pulmonary embolism.

Destruction of lymphocytes leads to lymphocytopenia.

An increase in creatine kinase is an indicator of muscle damages.

The depletion of the ACE2 receptors in the endothelial cells of the blood vessels also causes many cardiovascular irregularities.

ACE2 receptors are also highly expressed in the differentiated epithelial layers of the small intestine. In a later stage when the virus spreads its infection in this area it causes diarrhea.

In general people with cardiovascular problems must be careful as they are more prone to be seriously affected by COVID-19 infection disregarding their age and sex.

Treatment Options and Trials:-

Soluble ACE2 injections:-

There are two types of ACE-2 that are available in our bodies.

1. Cell bound ACE2 which acts as an enzyme as well as a receptor by which the COVID-19 enter into the cell.

2.Soluble ACE2 which is circulating in our body fluids widely and attracting too the coronavirus but does not help the virus to enter into the cell.

Both enzymes are downregulating the RAAAS and produce beneficial effects of easing hypertension, inflammation, pneumonia, and cardiac injuries.

But soluble ACE2 is beneficial over the tissue bound ACE2 as it does not help the virus to damage the cell.

But still, it is under trial.

Angiotensin Receptor Blockers (ARB): ARBs are safe drugs and selectively block ATR-1.This selective blockade has a benefit of easing hypertension, inflammatory secretions, thick mucus formations, pneumonia, hypoxia, and cardiac injuries.

ACE-1 Inhibitors-ACEI:-

ACE-1 inhibitors inhibit the action of ACE-1 and thereby prevent the conversion of angiotensin-I to angiotensin-II. Similar to ARBs these drugs also ease hypertension, reduce inflammatory secretions, and thereby reduce the formation o thick mucus, acute respiratory distress (ARD). These drugs are more potent than ARBs but have more side effects.

But the above-described benefits are all only theoretical and practically they do not yield many benefits.

Some times they exaggerate the effects of COVID-19 for reasons which are not yet clear.

Hence those blood pressure patients who are tested as COVID-19 positive should not discontinue their B.P medications such as captopril, enalapril, and telmisartan, olmesartan without their doctor's advice.
ESTROGEN-BENEFITS

Interestingly, young women are safer than young men from COVID-19 disease and its harmful cardiovascular effects. This is because of the protective nature of the estrogens the female sex hormones secreted from the ovaries of the young women.

Estrogens have some health benefits for younger women including cardiovascular and bone health such as,

1. Stimulate calcium and phosphorous homeostasis to form strong bones and thus prevent osteoporosis.

2.A balanced distribution of fat throughout the body.

3.Increasing blood HDL (good cholesterol)

4.Decreasing blood LDL (bad cholesterol)

5. Dilate blood vessels, ease blood flow, and thereby limiting hypertension.

6. The latest study says that estrogens have an anti-inflammatory effect in the brain and are antioxidant in nature and thus have many cardio and pulmonary (lungs) protective benefits including anti-asthmatic and anti-ischemic effects.

Fortunately, these merits of estrogens for a woman outweigh their demerits.

The woman who attained menopause and the woman who undergone an ovary removal (ovariectomy) surgery is at equal risk with aged and immuno-compromised men in COVID-19 disease.

Conclusively those who are associated with cardiovascular diseases must be careful and should have sufficient protective measures from the infection of this deadly COVID-19 disease.