COVID-19: A thread to share some thoughts and events

Proton-pump inhibitor? Someone tried that?

I think you have something like Omeprazole in mind? Which is a PPI for GERD. My guess is (and it is a guess) that different drugs will be specific for different types of cells. So Omeprazole may be a remedy for gastric issues, but may not be of use in alveoli. Chloroquine can only be a temporary measure too, because you don't want to prevent lowering pH in non-infected cells. Such side effects need clinical trials to establish efficacy, which presumably is going on right now.

There is something unusual about Germany's handling of COVID-19. They have a high incidence of infection but a very low death tally - much less than the UK, Italy, France or Spain. Are they catching cases earlier (through testing) and avoiding the onset of serious symptoms? Or have they a drug in use such as Chloroquine which is making the difference?

I heard something important tonight on TV. In an interview with specialists involved in case management, it was stated that COVID-19 may not be so much a respiratory problem as a blood micro-clotting problem. They seem to be witnessing these clots in the fatal cases. This may be the initiator of the Cytokine Storm issue. It was also suggested that using a ventilator may not be the best treatment. The use of CPAP devices and assisted Oxygen at higher levels (than would normally be considered) could well be the gold standard, and pull people round earlier and avoid the most serious symptoms (which would demand a ventilator).

Edit for #125 - I'd also like to correct an inaccuracy... The mRNA is released and enters the Nucleus for Influenza Viruses only. This does not happen with Corona Viruses. They are released outside the Nucleus. Proteins are then formed first which initiate production of sub-genomes (smaller than full length mRNA) that go on to synthesize other Polymerases to make all the bits for the corona complex. And it does get very complex! But such complexity gives more opportunity for intervention too - you only need to mess up the mechanism in one place to defeat producing "good" viral copies!
 
Energy considerations

One aspect of cellular infection by viruses - that has important implications for the symptoms we shall experience - is the demand for ENERGY. Most of us have experienced the intense feeling of being tired and drained when sick with flu. But we probably have not considered the true reason of why this happens. COVID-19 is now reminding sufferers in a dramatic way.

For a virus to "get going" inside a cell, there is a lot of synthesizing and bonding of proteins needed to make complex structures and configurations. These new structures then proceed to work upon translating sub-genomic strands of mRNA as part of the whole mechanism to copy the virion particle. Bonding in particular consumes large quantities of energy.

All of this type of intracellular activity is additional to the normal human biological functions that are already taking place within a cell. So the total demand for ENERGY is suddenly much greater than that we would normally require for daily life. Viruses are insidious parasites and they have evolved ways of hi-jacking the standard energy producing pathways in order that they take precedence in the queue for energy consumption. They even create new proteins that can inhibit the normal cellular functions to make sure that their processes get preferential treatment by the cells traditional cycles, such as the Citric Acid Cycle (Krebs Cycle).

It is not surprising then that a "key symptom" of COVID-19 is exhaustion.

I'm wondering now if this might lead to a further clue for those individuals who are COVID-19 asymptomatic? If they are indeed shedding virus particles - as the pundits seem to indicate is true - then such individuals would also need additional ENERGY requirements to the standard bodily needs. One reflection of this factor could be a reduction in body temperature below the average value of 37.0 degC.

This relationship between virus activity and ENERGY has another important potential long term consequence. Certain types of virus, such as Hepatitis C, can result in long term Glucose abnormalities - even when normal amounts of Insulin are present in the blood stream. The virus has altered some mechanisms of Glucose supply to its own advantages and the body now produces an excessive amount. Recently, this has been understood as one of the mechansim for acquiring Type 2 Diabetes. We have yet to understand what the long term implications of COVID-19 will be, but its probably a wise decision to monitor your Blood Glucose levels for some time into the future if you have recovered from infection.
 
The invisible enemy?

Would it be possible to view and detect SARS-CoV-2 using a conventional optical microscope? This corona virus has dimensions between 70 - 90 nm for a single virion particle.

With an optical microscope, conventional wisdom states that objects smaller than about 200 nm cannot be seen because of a restriction known as the "diffraction limit". At these dimensions, a transmission microscope (light coming from beneath a microscope slide) is unable to cast a sharp outline to the eyepiece due to bending of visible light around the object's outside edges. Two light rays travelling either side of such a small target would be diffracted and become merged together before they reached the first object lens - therefore no shadow image cast.

However, I came across a published article recently that may have a solution. This article was written in 2011, some nine years ago, and it uses tiny 200 um sized glass spheres to increase resolution beyond the diffraction limit... https://www.cnet.com/news/nanoscope-makes-live-viruses-visible-for-first-time/.

With this idea, the glass sphere is located almost in contact with the target object to be viewed. So light enters the sphere at a distance much less than the wavelength of light. It therefore picks up the "near-field" radiation, known as evanescent waves, which are not diffracted in the same way as "far-field" radiation. These evanescent waves contain a lot of the spacial high frequency content normally lost to a conventional microscope. That spacial high frequency is in effect the width distance of the target object in a form of "Fourier Transform" principle.

The claim is that this new technique can resolve width distances down to at least 50 nm, which should be more than ample to see the virion particle. It will not necessarily let you identify the type of virus, or indeed if it is a virus at all. But it will allow you to know that there is "something" of that dimension present in the sample you are looking at. If the sample was, say, saliva taken from a suspected asymptomatic person, then the presence of tiny particles of around 70/90 nm dimensions would be sufficient to trigger a more rigorous PCR test to confirm or otherwise whether the person involved is infected with COVID-19. It could do this very early on in the disease development phase and thereby reduce the chances of this person becoming a super spreader. It might also allow this person to be diagnosed before the disease takes full hold on invading further organs in the body - thereby saving their life.
 
New test technique

Interesting developments are now happening with COVID-19 antigen testing (the swab test - to see if you are currently infected). There is a new technique called LAMP (Loop mediated isothermal AMPlification) which is an alternative to using the PCR method. Turns out to be much faster and much simpler - it does not need to be sent off to a lab.

The virus RNA in a test sample has to be "amplified" up to the levels where it can be positively identified. The PCR technique requires temperature cycling in a predetermined manner of heating/cooling in complex lab machines, but the LAMP technique can be used at a constant (isothermal) temperature of 60/65 deg C. Using a simple "heating slab" device, the sample can be tested in the field and results obtained in 20 minutes.

Preliminary tests in the UK have been very encouraging. This was announced this week by our Health Secretary (https://www.bbc.co.uk/news/uk-52762153). But no doubt the LAMP principle will now be under research in a number of different countries.
 
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