The SARS-CoV-2 virus overactivates and disrupts the renin-angiotensin system (RAS) and we now understand better why some patients develop disabling diseases. Jean-Marc Sabatier explains.
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 RAS (also known as the angiotensin-aldosterone system or AAS). The RAS is responsible for renal, pulmonary, and cardiovascular autonomic (automatic) functions; it also controls innate immunity and various microbiota. The RAS is ubiquitous in the body (it is present in cells of various tissues and organs). The dysfunctional RAS (because overactivated) is directly responsible for Covid-19 pathologies via the exacerbated activity of its “deleterious” receptor AT1R. 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-fibrosing, pro-hypertrophying, and causes nitric oxide to fall (the latter is involved in inflammatory, immune and memory phenomena).
The overactivated RAS produces the release of a hormone: aldosterone
When the RAS is overactivated, the mineral corticoid 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). Aldosterone secretion is stimulated by angiotensin-2 or by an increase in blood potassium levels. 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 precisely regulate blood volume and blood pressure.
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 regulates blood pressure and hydration in the human body. Thus, the RAS overactivated by SARS-CoV-2 (or even -in some cases- by the vaccine Spike protein) induces hypokalemia, i.e. an insufficient level of potassium in the blood (< 3.5 mmol/L).
Hypokalemia causes disabling disorders (e.g., paralysis) of the Covid-19
In general, hypokalemia may result from poor potassium uptake or from extracellular potassium migration within cells. In practice, hypokalemia is mainly associated with potassium losses via the urine (micturition) or the gastrointestinal tract (vomiting or diarrhea, common in Covid-19). The most frequent cause of hypokalemia is therefore excessive renal and digestive losses. Diuretic use or adrenal gland damage may also be responsible for low blood potassium levels. Hypokalemia can also be due to the intra-cellular migration of potassium in case 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 to severe hypokalemia is accompanied by cardiac arrhythmias (extrasystoles, blocks, and ventricular/atrial tachyarrhythmias, ventricular fibrillation) which may lead to malaise, severe fatigue (myalgic encephalomyelitis or chronic fatigue syndrome), muscle weakness, cramps, pain, and muscle fasciculations/contractions, 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 (decreased oxygen saturation O2 of red blood cells) and hypercapnia (carbon dioxide overload of 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 down -or even a stopping- 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 normal potassium levels in the body (via intracellular potassium migration mediated by the Na+/K+-ATPase pump).
Symptoms and disorders related to hypokalemia are frequently observed in people with long-standing Covid, following natural infection and/or anti-Covid-19 vaccination. In the case of muscle weakness, hypokalemia as well as recent or old microbial infections (Influenza virus of the flu, 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 (hypomagnesemia) can cause hypokalemia. A potassium deficiency can be restored by a diet (or supplementation) rich in potassium (bananas, fish, beans, potatoes, etc.). However, it should be noted that hypokalemia is rarely related to insufficient potassium intake. If hypokalemia persists, the host may develop kidney problems, causing the frequent need to urinate and drink large amounts of water.
Glucose, insulin and hypokalemia
The RAS overactivated by viral Spike protein (during natural host infection with SARS-CoV-2) or sometimes vaccines (Spike protein from vaccines) is dysfunctional. Dysfunctional RAS induces glucose intolerance (pre-diabetes type 2 state) via overactivation of its “deleterious” AT1R receptor. In people with long-standing Covid, it has been observed that intake of high-carbohydrate foods (chocolate bars, sugar, sweets, etc.) can 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 of the pancreas), a hypoglycemic hormone involved in the regulation of blood glucose levels. Insulin causes hypokalemia (by stimulating a Na+/H+ exchanger that increases intracellular sodium, the latter activating the Na+/K+-ATPase pump that internalizes potassium (2 K+) by releasing sodium (3 Na+) into the extracellular medium). These events provide elements of response to potential and recurrent “relapses” (to date unexplained) related to high carbohydrate food intake.
In summary, hypokalemia (or low blood potassium) induced by RAS dysfunction and angiotensin-2 excess (inducing overactivation of the RAS AT1R receptor) contributes to the many more or less disabling pathologies of Covid-19 and Covid long. 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 a research director at the CNRS and holds a doctorate in Cell Biology and Microbiology and an HDR in Biochemistry. Editor-in-Chief of the international scientific journals: “Coronaviruses” and “Infectious Disorders – Drug Targets”. He speaks here in his own name.