Magnesemia key to Hypokalemia, COVID-19 damage?

Magnesemia is the name for magnesium deficiency.
Magnesemia  can cause hypokalemia (potassium deficiency.)
Hypokalemia is reported in nearly all COVID-19 patients.
Could Magnesium be the key to understanding the disease in a way to improve patient outcomes?

In early 2015, I wrote an article about fluorescence and medicine, in which I discussed porphyrins, calcium, and magnesium.  
In early 2019, I further explored the possible medical relevance of Vitamin D to regulation of magnesium.
This prepared me to think about how magnesium plays a role in the current COVID-19 pandemic.

In January 2020, I noted that "Another coronavirus, SARS, has an exoribonuclease that requires Mg2+ as a cofactor. So if I am correct that Vitamin D3 regulates Mg availability, then D3 affects SARS-CoV."
What is an exoribonuclease?  It's another pair of scissors.  In my last post, I talked about how phospholipase is like a pair of scissors powered by a phosphorus and specialized to cut phospholipids.  In this post, we'll consider that exoribonuclease is a pair of scissors activated by Magnesium and specialized to cleave off parts of RNA.

Per Wikipedia, 
   "Exoribonucleases are involved in the degradation of many different RNA species, including messenger RNA, transfer RNA, ribosomal RNA and miRNA."
When I searched PubMed for 
   exoribonuclease pulmonary
I happened across a 2015 discovery that an exoribonuclease PARN is associated with unexplained cases of pulmonary fibrosis. 
That exoribonuclease problem in the lungs sounds suspiciously like the lung problems in COVID-19, the disease which is caused by the virus SARS, which is closely-related to the virus SARS-CoV-2, which is causing the current pandemic and which requires Magnesium as a cofactor for its pair of scissors (its exoribonuclease.)  What type of RNA is SARS-CoV-2 cutting up, and why?  
For the virus, is this how it gets some of the supplies it needs to manufacture new copies of itself?  
For the body, does that RNA degradation prevent a message from getting through? Does it mean some biological process never receives a "stop" or a "go" signal?  Or is DNA replication disrupted or distorted?
Those questions are worthy pursuits for a researcher.  If I were a researcher, I would take that PARN discovery and look specifically at telomeres and RNA primers.

I cannot explain how and why SARS scissors cleave RNA, but I can speculate that by controlling the availability of Magnesium, the immune system can control the activity of the virus.  Vitamin D helps regulate Calcium, and as previously mentioned, I have provided experimental evidence that Vitamin D also helps regulate Magnesium.

Our bodies need Magnesium to function.  Magnesium is stored in our bones, tissues, and fluids.  But the virus also needs Magnesium--to activate its scissors to chop up our RNA.  Is it plausible that the body temporarily decreases the available Magnesium in order to deprive the SARS-CoV-2 virus of the ability to cut our RNA?  In that case, a patient's body would not be deficient of magnesium, per se, but merely it would cut down the supply available to the virus.  I infer this would result in hypomagnesemia, a shortage of magnesium in blood. If so, then the kidneys are the organ regulating magnesium in serum.

If it is detected, hypomagnesemia can be treated.

But if we are low on Magnesium, it can cause potassium deficiency--hypokalemia, and hypokalemia is more likely to be noticed and treated.

Hypokalemia is reported in nearly all COVID-19 patients.

The common-sense treatment for hypokalemia is to give potassium fluids to the patient, but if the underlying cause is hypomagnesemia, then the patient may not get the benefit of the potassium administered.

Even worse, if the patient is hypokalemic because of hypomagnesemia, then I speculate that any treatments also having a negative effect upon magnesium could worsen the problem.  Consider reading the National Institutes of Health fact sheet on Magnesium.

The most relevant part is right here:

Interactions with Medications

Several types of medications have the potential to interact with magnesium supplements or affect magnesium status. A few examples are provided below. People taking these and other medications on a regular basis should discuss their magnesium intakes with their healthcare providers.

Bisphosphonates

Magnesium-rich supplements or medications can decrease the absorption of oral bisphosphonates, such as alendronate (Fosamax®), used to treat osteoporosis [62]. Use of magnesium-rich supplements or medications and oral bisphosphonates should be separated by at least 2 hours [58].

Antibiotics

Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline (Declomycin®) and doxycycline (Vibramycin®), as well as quinolone antibiotics, such as ciprofloxacin (Cipro®) and levofloxacin (Levaquin®). These antibiotics should be taken at least 2 hours before or 4–6 hours after a magnesium-containing supplement [58,63].

Diuretics

Chronic treatment with loop diuretics, such as furosemide (Lasix®) and bumetanide (Bumex®), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H®) and ethacrynic acid (Edecrin®), can increase the loss of magnesium in urine and lead to magnesium depletion [64]. In contrast, potassium-sparing diuretics, such as amiloride (Midamor®) and spironolactone (Aldactone®), reduce magnesium excretion [64].

Proton pump inhibitors

Prescription proton pump inhibitor (PPI) drugs, such as esomeprazole magnesium (Nexium®) and lansoprazole (Prevacid®), when taken for prolonged periods (typically more than a year) can cause hypomagnesemia [65]. In cases that FDA reviewed, magnesium supplements often raised the low serum magnesium levels caused by PPIs. However, in 25% of the cases, supplements did not raise magnesium levels and the patients had to discontinue the PPI. FDA advises healthcare professionals to consider measuring patients’ serum magnesium levels prior to initiating long-term PPI treatment and to check magnesium levels in these patients periodically [65].

I reiterate my previous Twitter threads saying that experts need to do an end-to-end assessment of interdependencies of drugs that are used in treating COVID-19 patients.  I specifically zeroed in on how medications affect Magnesium and affect Tryptophan, but other analytes and pathways should be considered, e.g. Effects upon IFN-gamma? IDO? XO & UA?  Choice of antibiotic, anaesthesia, anti-nausea, and other medicines should be evaluated in light of this novel virus, how it attacks the body, and how the body reacts.

Also, relevance of patient medicines should be considered carefully, for example proton pump inhibitors as mentioned on the NIH page and in other research.

For additional reading on hypomagnesemia, see this excellent article, which mentions a tie-in with another interesting topic, Transient Receptor Potential channels (TRPM6 and TRPM7).  It also provides further details on serum magnesium (e.g. 1/3 of serum Mg is in protein, bound mostly to albumin.)  Furthermore, it mentions the diuretic amiloride as magnesium-sparing (decreases magnesium excretion.) 

To my eye, the structure of Amiloride looks somewhat related to a drug that has been in the news regarding COVID-19: chloroquine.  For that reason, and for the relationship between Phospholipase A2 and chloroquine which I explored in my previous post, I looked up on PubMed
   Amiloride PLA2
Fascinating.  12 results, with titles referring to topics I have discussed: Vitamin D, viruses (parvovirus), arachidonic acid (see my last post re PLA2), DNA synthesis (which we mentioned in this post when discussing telomeres), and angiotensin II (related to the ACE2 receptor by which SARS-CoV-2 invades our cells), 

For COVID-19, we have much to learn about how the virus attacks, and much to learn quickly about which drugs can thwart that attack, and how those drugs do so.  Previous research may already have uncovered clues and answers that will help us end the pandemic.