Covid-19 Acquired Adenosine Deaminase 2 Deficiency?

May 30, 2020
COVID-19 is increasingly associated with peculiar observations such as teenage strokes, child Kawasaki Disease, multi-organ involvement, immune, thrombocytopenia and clotting irregularities, inflammation and, of course, cough and hypoxia. I’d like to make the case for Virally Acquired Adenosine Deaminase Deficiency and closely associated enzyme irregularities in Covid-19.

The enzymes I propose to be involved are closely biologically or physically coupled. DPPIV/CD26 is membrane bound by Adenosine Deaminase 2 whilst the latter is closely biologically coupled to the activities of Glucose 6 Phosphate Dehydrogenase. Adenosine status regulates all three.
I propose the problem can be explained by Acquired Adenosine Deaminase Deficiency (which could be because the virus retains the ability to target DPPIV which is membrane bound by Adenosine Deaminase 2 as per SARS and MERS). Did we take our eye off the ball as soon as ACE2 became implicated as a receptor?

Blacks and Asians have a high incidence of Glucose 6 phosphate Dehydrogenase Deficiency and the UK ‘BAME’ population are 3x more likely to be admitted to hospital even though the smoke half as much as Whites and Mixed. G6PD Deficiency promotes endothelial oxidative stress and decreased endothelial vasodilatory Nitric Oxide availability (note Nitric Oxide showing promise as a therapy). G6PD is also deeply implicated in Kawasaki Disease, (for example: as associated with Covid-19 in children and the Lividoid rash common to both. G6PD is one step away from Adenosine Deaminase which also results in platelet abnormalities. Both enzymes cause a condition called Severe Combined Immune Deficiency. Lack of DPPIV (also known as CD26 and is an Angiotensin Converting Enzyme) can lead to vascular permeability because it does not deactivate Substance P (or Bradykinin responsible for cough).

I have put together a basic video (below) to draw attention to DPPIV/CD26 and Adenosine Deaminase 2 as ‘Ground Zero’. No dispute that ACE2 is involved and disruption would certainly also reduce the expression and activity of DPPIV. Adenosine receptors also produce surfactant in Alveoli and a back-up in processing Adenosine Diphosphate would explain low platelet count and aggregation.

Perhaps the most interesting point of all is that Adenosine converts to Inosine only in Hypoxic conditions and it serves as a key counter-regulator of hypoxia. This appears mostly due to vascular tone and a direct effect on levels of 2,3-Bisphosphoglycerate which facilitates Haemogloin release of oxygen to hypoxic tissues. It appears severe covid-19 patients are relying upon an evolutionary-conserved bio-mechanism that ordinarily isn’t needed because Adenosine Deaminase serves that function without need to reach hypoxic levels.

The biology is entirely related to respiration, oxidative stress control, electron transport, inflammation and Immune modulation. DPPIV/ CD26 and Adenosine Deaminase are the perfect place to start if you wanted to engineer a disease like Covid-19. I’m not supportive of the idea that it has been bio-engineered but if there were only one enzyme one could attack it would have to be Adenosine Deaminase 2 because DPPIV/CD26 also depends upon it and it has other effects, the second choice would be ACE2. Type 2 Diabetics have a head start because they tend to be taking DPPIV inhibitors already and have other related glucose and hypertensive issues.

My single-handed progress so far:

An in-depth understanding of the mechanism that SARS-CoV2 uses will lead to therapies. My current target — subject to confirmation — is myo-inositol which is otherwise considered to be non-essential but that’s different if both G6PD and Adenosine Deaminase pathways are disrupted. My hope is that others will agree that the evidence points towards the described deficiencies and that will lead to increased focus in this particular area. Please share this with any interested physician or scientist.


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