The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. It is physiologically significant in capillary microcirculation and in fluid distribution to the tissues. Human serum albumin (HSA), the most abundant protein in plasma, is created in the liver which also maintains its concentration, but this reduces by 10-15% after 50 years of age. HSA transports hormones, free fatty acids and maintains oncotic pressure, but SARS-CoV-2 virions bind competitively to HSA diminishing its normal transport function. Furthermore, hypoalbuminemia is frequently observed in patients with such conditions as diabetes, hypertension, and chronic heart failure, i.e., those most vulnerable to SARS-CoV-2 infection. Hypoalbuminemia, coagulopathy, and vascular disease have been linked in COVID-19 and have been shown to predict outcome independent of age and morbidity. Hypoalbuminemia is also known factor in sepsis and Acute respiratory distress syndrome (ARDS) occurs when fluids build-up in the alveoli and it is associated with sepsis, whose mechanism is systemic, being associated with the fluid and logistic mechanisms of the circulation. Glycocalyx damage is associated with changes plasma protein concentration, particularly HSA and blockage of albumin transport can produce the systemic symptoms seen in SARS-CoV-2 infection and sepsis. We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites. We postulate that albumin therapy to replace bound albumin might alleviate some of the symptoms leading to sepsis and that clinical trials to test this postulation should be initiated as a matter of urgency.

At present the neurological basis of sentience is poorly understood and this problem is exacerbated by only a partial knowledge of how one of the primary elements of sentience, the action potential, actually works. This has consequences for our understanding of how communication within the brain and in artificial brain neural networks (BNNs). Reverse engineering models of brain activity assume processing works like a conventional binary computer and neglects speed of cognition, latencies, error in nerve conduction and the true dynamic structure of neural networks in the brain. Any model of nerve conduction that claims inspiration from nature must include these prerequisite parameters, but current western computer modeling of artificial BNNs assumes that the action potential is binary and binary mathematics has been assumed by force of popular acceptance to mediate computation in the brain. Here we present evidence that the action potential is a temporal compound ternary structure, described as the computational action potential (CAP). The CAP contains the refractory period, an analog third phase capable of phase-ternary computation via colliding action potentials. This would best fit a realistic BNN and provides a plausible mechanism to explain transmission, in preference to Cable Theory. The action potential pulse (APPulse), is made up of the action potential combined with a coupled synchronized soliton pressure pulse in the cell membrane. We describe a model of an ion channel in a membrane where a soliton deforms the channel sufficiently to destroy the electrostatic insulation thereby instigating a mechanical contraction across the membrane by electrostatic forces. Such a contraction has the effect of redistributing the force lengthways thereby increasing the volume of the ion channel in the membrane. Na ions, once attracted to the interior, balance the forces and the channel reforms to its original shape. A refractory period then occurs until the Na ions diffuse from the adjacent interior space. Finally, a computational model of the action potential (the CAP) is proposed with single action potentials significantly including the refractory period as a computational element capable of computation between colliding action potentials.

Substantial evidence has accumulated to show that the action potential is always accompanied by a synchronized coupled soliton pressure pulse in the cell membrane, the action potential pulse (APPulse). Furthermore, it has been postulated that, in computational terms, the action potential is a compound ternary structure consisting of two digital phases (the resting potential and the action potential) and a third-time dependent analogue variable, the refractory period. Together, with the APPulse, these phases are described as the computational action potential (CAP), which allows computation by phase. The nature of transmission, and thus computation across membranes, is dependent upon their structures, which have similar components from one neuron to another. Because perception and therefore sentience must be defined by the capabilities of the brain computational model, we propose that phase-ternary mathematics (PTM) is the native mathematical process underlying perception, consciousness and sentience. In this review, we take the CAP concept and apply it to the working of a well-defined neural network, the vertebrate retina. We propose an accurate working computational model of the retina and provide an explanation of computation of the neural transactions within it using PTM, and provide evidence that could form the basis of understanding neural computation within the entire nervous system. Evidence is presented of phase ternary computation (PTC), defined in phase ternary mathematics and shows an exact mathematical correlation between the activity of the amacrine cells, the bipolar cells and ganglion cells of the retina, once these cells have been activated by light falling on the cones. In this model, the computation of luminosity of multiple cones synapsed to a bipolar cell is performed by phase ternary mathematics at the points of convergence of CAPs. Redaction by the refractory periods of converging CAPs eliminates all but the leading APPulse resulting in sampling and averaging. In phase ternary analysis (PTA), the physiology of synapses defines their primary action as latency changers, changing the time taken for impulses to travel between points of convergence. This paper describes a novel type of computation, PTC, with evidence that it is the fundamental computational method used by the retina and by association the rest of the brain. By comparing the morphology of neurons it is now possible to explain their function singly and in networks. This has profound consequences both for our understanding of the brain and in clinical practice.

COVID-19 and long COVID-19 vulnerabilities may be caused indirectly by albumin binding deficiency (ABD), which can be corrected by the correct administration of human serum albumin (HSA). The liver is the primary site of nutrient regulation and fluid volume maintenance; control of both is by changes to albumin concentration. In healthy subjects, the HSA lymphatic nutrient pump (HSALNP) ensures continual pumping of nutrients from the liver and that nutrients are appropriately distributed to organs. Nutrients are delivered to cells according to the availability of binding to HSA. The HSALNP, therefore, maintains the correct nutrient and colloidal pressure balance in all tissues independently. In unhealthy tissues, following COVID-19 infection, the passage of HSA/nutrients through the interstitial spaces and lymph will be impeded. Fluid therapy into the periphery leads to the dilution of essential nutrients attached to the protein carriers such as albumin. The levels of albumin being charged by the liver with nutrients is critical in maintaining immune stability by maintaining nutrient support and colloidal pressure of the cellular structures. The site of HSA binding by the liver is of great importance, and direct infusion of albumin into the hepatic portal vein is the most appropriate method of maintaining colloid pressure and cellular nutrient levels.

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