The SARS-CoV-2 virus overactivates and disrupts the renin-angiotensin system (RAS) and we now understand better why some patients develop disabling diseases. Explanations by Jean-Marc Sabatier.
By Jean-Marc Sabatier*
The SARS-CoV-2 virus causes the overactivation (and disruption) of a key physiological system for the functioning of the human body: the renin-angiotensin system or ARS (also called the angiotensin-aldosterone system or RAAS). The ARS is responsible for autonomic (automatic) renal, pulmonary, and cardiovascular functions; it also drives innate immunity and various microbiota. RAS is ubiquitous in the body (it is present in cells of various tissues and organs). The dysfunctional RAS (because it is overactivated) is directly responsible for Covid-19 pathologies via the exacerbated activity of its “deleterious” AT1R receptor. Indeed, the overactivated AT1R receptor has many harmful activities, as it is pro-hypertensive, pro-inflammatory, pro-oxidant, pro-thrombotic, pro-angiogenic, pro-hypoxemic, pro-hypoxic, pro-fibrotic, pro- hypertrophic, and lowers nitric oxide (the latter is involved in inflammatory, immune and memory phenomena).
The overactivated RAS produces the release of a hormone: aldosterone
During overactivation of the RAS, the corticosteroid mineral hormone aldosterone is secreted by the adrenal glands. Aldosterone helps maintain the balance between sodium and potassium (which are two electrolytes in the body that carry a positive electrical charge when present in body fluids, including blood). The secretion of aldosterone is stimulated by angiotensin-2 or by an increase in kalemia (potassium level in the blood). The role of aldosterone is the reabsorption of sodium in the kidney (via the cells of the distal tubule of the nephron), and the secretion of potassium in the urine in order to regulate – with precision – volemia (blood volume) and blood pressure arterial.
Water and sodium retention
The kidneys, which mainly regulate the balance of sodium, chloride and potassium, filter about 800 millimoles of potassium per day. The retention of sodium in the body (thanks to aldosterone) initiates a phenomenon of osmosis allowing the retention of water and sodium (in the form of salt) in the blood vessels (= vascular system). This results in an increase in blood volume, and therefore, in blood pressure (hypertension). Aldosterone therefore allows the regulation of blood pressure and hydration of the human body. Thus, SRA overactivated by SARS-CoV-2 (even – in some cases – by the vaccine Spike protein) induces hypokalaemia, that is to say an insufficient level of potassium in the blood (< 3.5 mmol /I).
Hypokalemia at the origin of disabling disorders (eg paralysis) of Covid-19
In general, hypokalemia can result from poor potassium absorption, or from extracellular potassium migration into cells. In practice, hypokalemia is mainly associated with losses of potassium via the urine (urination) or the digestive tract (vomiting or diarrhea, frequent in the event of Covid-19). The most common cause of hypokalemia is therefore excessive kidney and digestive loss. Taking diuretics or damage to the adrenal glands can also respond to a low blood potassium level. Hypokalemia can also be due to the intracellular migration of potassium in the event of stress, metabolic alkalosis (accumulation of bicarbonate HCO3-), intake of food with a high carbohydrate index inducing the secretion of insulin, caffeine , theophylline, or specific drugs (including beta-2-mimetic bronchodilators). Mild hypokalemia may be asymptomatic. Moderate or severe hypokalemia is accompanied by cardiac arrhythmia (extrasystoles, blocks, and ventricular/atrial tachyarrhythmias, ventricular fibrillation) which can lead to malaise, intense fatigue (myalgic encephalomyelitis or chronic fatigue syndrome), muscle weakness, cramps, pain and muscle twitching/twitching, including (mostly transient) muscle paralysis. Severe hypokalemia potentially results in (i) arterial hypotension, (ii) pulmonary hypoventilation (insufficient air supply to the lungs) leading to hypoxemia (decrease in the O2 dioxygen saturation of the red blood cells of the blood) and hypercapnia (overload of carbon dioxide CO2 in arterial blood) leading to acidification of the blood (voluntary hypoventilation is found in some athletes), and (iii) paralytic ileus (intestinal paresis corresponding to a slowing -or even a stoppage- of intestinal transit or severe constipation).
Possible kidney problems
It is important to mention that hypokalemia and associated pathologies can occur in the presence of a normal level of potassium in the organism (via the intracellular migration of potassium mediated by the Na+/K+-ATPase pump).
Symptoms and disorders related to hypokalaemia are frequently observed in people suffering from a long Covid, following a natural infection and/or an anti-Covid-19 vaccination. In the case of muscle weakness, hypokalemia as well as recent or old microbial infections (Influenza virus of influenza, Epstein-Barr herpes virus of infectious mononucleosis and others) are to be considered. Blood potassium deficiency is associated with the appearance of more or less disabling pathologies, because this mineral is essential for the proper functioning of cells, nerves or muscles (and others). A low blood level of magnesium (hypomagnesaemia) can cause hypokalaemia. A potassium deficit can be restored by a diet (or supplementation) rich in potassium (banana, fish, beans, potato, etc.). However, it should be noted that hypokalaemia is rarely linked to an insufficient potassium intake. In the event of long-lasting hypokalaemia, renal disorders may appear in the host, causing the frequent urge to urinate and drink large quantities of water.
Glucose, insulin and hypokalemia
The RAS overactivated by the viral Spike protein (during a natural infection of the host with SARS-CoV-2) or sometimes vaccinal (Spike protein from vaccines) is dysfunctional. Dysfunctional RAS induces glucose intolerance (pre-diabetes type 2 state) via the overactivation of its “deleterious” AT1R receptor. In people suffering from long Covid, it has been observed that taking food with a high carbohydrate index (chocolate bar, sugar, sweets, etc.) could lead to an exacerbation of disabling Covid-19 pathologies. Such foods induce the secretion of insulin (from the beta cells of the islets of Langerhans in the pancreas), a hypoglycemic hormone involved in the regulation of blood glucose levels (regulation of blood sugar). Insulin causes hypokalaemia (by stimulating a Na+/H+ exchanger which increases intracellular sodium, the latter activating the Na+/K+-ATPase pump which internalizes potassium (2 K+) by releasing sodium (3 Na+) into the extra medium -cellular). These events provide some answers to potential and recurrent “relapses” (as yet unexplained), linked to the intake of food with a high carbohydrate index.
In summary, hypokalemia (or low blood potassium) induced by RAS dysfunction and excess angiotensin-2 (inducing overactivation of the RAS AT1R receptor) contributes to the many more or less disabling pathologies of Covid -19 and long Covid. These data are of interest for the understanding and treatment of Covid-19 diseases, including (temporary) paralysis and chronic fatigue syndrome (myalgic encephalomyelitis), which represent the most severe and mysterious forms.
*Jean-Marc Sabatier is research director at the CNRS and doctor in Cellular Biology and Microbiology, HDR in Biochemistry. Editor-in-Chief of international scientific journals: “Coronaviruses” and “Infectious Disorders – Drug Targets”. He speaks here in his own name.
