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Native Answers Coronavirus Related Basic Science Questions

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Native

ToungeInCheek since 2010
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5 Year Member
If I understand it correctly, IgM is the initial antibody response post-infection, and is short lived, and IgG is the "memory" antibody that would enable the host to fight off subsequent infections, right?

So when researchers are looking at subsequent immunity, they would be looking for the IgG antibody? Would there be a difference in IgG levels based on the severity of symptoms?
That is correct. It is the process of class switching that allows the immunoglobulins end up IgG1 IgG2 IgA, IgD etc. IgM lacks the specificity. I get out of my element fairly quickly when talking immunology.
 

Native

ToungeInCheek since 2010
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Is this risk for pregnant woman more significant?
Basically it is not know at this point. Our grand rounds was broadcast and IT sucks and my stream literally was cutting out when that subject was brought up this morning.

From WHO
As opposed to Influenza A(H1N1) pregnant women do not appear to be at higher risk of severe disease. In an investigation of 147 pregnant women (64 confirmed, 82 suspected and 1 asymptomatic), 8% had severe disease and 1% were critical.

The N (147) right now is too small to really know anything.
 

Native

ToungeInCheek since 2010
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5 Year Member
chloroquine phosphate is showing strong results against COVID-19 infections in both China and South Korea.
Remdesiver is a nucleotide analog. As the main genetic material is RNA, the virus has to make it's own RNA for replication. Eukaryotic/mammalian cells follow central dogma and go DNA>RNA>Protein. So the virus makes its own unique RNA dependent RNA polymerase to get the additional copies of its genetic material. (never goes to DNA) So this is RNAdepRNApol is unique and they screen nucleotide analogs to find one that it will accept that is wrong. This incorporates into the genome instead of adenosine (A) and slow/arrests viral replication.

Chloroquine is a malarial drug that leads to cellular acidification. Essentially making it hard for plasmodium to live, and in the case of a virus, prevent capsid assembly to work appropriately. Basically the chemistry of making the viral capsid parts come together falters and new viral particles are not formed.
 
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Native

ToungeInCheek since 2010
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5 Year Member
@Native What is your opinion on these drugs and other anti virals such as Tamiflu and Acyclovir for treating coronavirus?
Tamiflu is a neuramidase inhibitor. It blocks the cleavage of sialic acid which is required for viral particle release in influenza. Not the mechanism of exit for coronavirus, so it doesn't stand a chance to work.

Acyclovir binds to DNA based virus' DNA polymerase, so again, a different antiviral target that coronavirus lacks.

I believe the protease inhibitors that are used in HIV treatment have a better chance at showing some success. In mammalian cells it is one gene one protein. Viruses often have multiple proteins made off of a single transcript. This mean that the proteins are hooked together as a polypeptide and have to be cleaved to become functional. This occurs with COVID, so I know some of them such as nelfinavir are being looked at and have some laboratory success. I don't know on the current therapeutic use of protease inhibitors.
 
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Native

ToungeInCheek since 2010
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Nobody asked, but I am telling you anyway.

From New England Journal of Medicine today. 1/2 life of viability in aerosol is roughly 1 hr. (doesn't mean will stay in air). Rapid decay and ability to detect live virus on various surfaces all show that the titer(viable virus count) drop to below the limit of detection by 80 hrs, just over 3 day on the longest lasting surface.

I see a lot of stuff about how long it survives where. Wash your hands, don't lick inanimate objects. don't be afraid of the world.

And do not waste your time holding breath for 10s as some form of pseudoscience self test. What a joke.

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Native

ToungeInCheek since 2010
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No conspiracy theories needed. New infections crossing from animals to humans are going to happen.

 

Native

ToungeInCheek since 2010
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5 Year Member
Has been hint upon a bit in this thread, but not many details at this point are known. In post #10 I bring up how the IgM/IgG antibody testing is going to be important to understand the scope of the infection and then be used to help determine how long lived the immune response is going to be. Unfortunately, with common colds, the immune response often isn't "durable", meaning that our antibody response isn't stimulated enough to get the body to move much beyond it's innate response to a virus. Innate response meaning, what we have in place at all times to combat any virus. A durable immune response is going to provide specific lasting protection. Even this type of protection fades over time, and it the reason why a good immune response such as the one to tetanus requires the booster. Gotta keep those memory B-Cells around to provide all the antibody we need when we step on that rusty nail.

So, the question remains, are we going to get antibody class switching that delivers long-term protection. This isn't completely known, and the few cases you see reporting re-infection are likely not fully vetted and often involve someone who never actually cleared the infection the first time.

This is a lay article reporting on a pre-print(not fully reviewed by science community) that demonstrates that at least rhesus macaques appear to have some lasting immunity, and provides support for the idea of using serum from recovered individuals as a method to treat people who are infected.

 

Native

ToungeInCheek since 2010
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How the Coronavirus test works:

Covid-19 is an RNA based virus that uses RT-PCR

The process of testing is essentially this:
1. Get a nasopharyngeal swap sample.
2. Isolate RNA from this swab. (~1 hr)
3. Convert RNA into DNA with reverse transcriptase enzyme. (RT) (~30min)
4. Amply coronavirus specific DNA through a process called polymerase chain reaction. (PCR) (~1.5hr)

So, if you are going to do this thoroughly, and in a manner that is scalable you want to have kits and machines that can do most of these steps, also have very few reagents that one has to mix together so that the Med tech can perform the test correctly every time, even on a night shift without screwing up. My time estimates are crude and depending on a variety of factors can be shifted one way or another. Once a lab receives the sample and they were ready to go and only did that it would be reasonable to have results in less than 4 hrs.

This is more automated and uses fancier machinery than what I would use in a lab and also you more of those fancy things called "controls". For thoroughness sake, 3 different regions of RNA that are specific and conserved in the coronavirus genome would be selected for amplification. This is done by carefully designing oligonucleotides (primers) that align perfectly with the CV sequence. After the RT step, PCR exponentially amplifies the specific chromosome regions. The growing amount of product has a third short primer that has two additional molecules added to the ends of them. This probe will bind to the PCR products. In each round of amplification or cycle, the enzyme that makes another product actually is a dual function enzyme that breaks down any piece of DNA (or probe in this case) that is in the way. Breaking down the probe these two molecules are released. They are actually a fluorophore and a quencher. When they are tethered together with the probe they do not emit or become exited. When they are free in solution they do. So the fancy RT-PCR machines are able to read the amount of fluorescence that accumulates with each cycle. The fancier the machine and with different fluorophores these reactions can be done in same tube at same time and are considered multiplexed. This test needs validated with positive (known coronavirus samples) and with negative controls, (not adding RNA early on) and optimization of timing and cleanliness of the readout for certification purposes. But that is essentially the process.



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Native

ToungeInCheek since 2010
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5 Year Member
Good thread about vaccine. Don’t know this dude either. But info lines up with what I’ve been told/taught.

 

Native

ToungeInCheek since 2010
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5 Year Member
Works Herd GIF


This is my favorite gif that shows how herd immunity works. It is based on mathematical modeling to show how an immune or vaccinated population is able to slow down the spread of a virus. In the coronavirus world, we are a naive population, with 0% infected or vaccinated. Here the new cases in red proliferate wildly until almost all experience the disease. As we as a society become immune or have had the infection, (increased vaccination rates) the spread of the disease is slowed down significantly.

The UK almost went with this model, to try and develop heard immunity, but have since closed schools and are also in "flatten the curve" mode. Herd immunity works a whole lot slicker when achieved by vaccination rather than actual disease, because you get to avoid the whole "oh crap, everyone might need a ventilator at once option".

I don't think we, as a society, could have all determined that, "okay, all of you who are healthy go lick ice cream cones together and if you are at risk avoid everyone who went to the ice cream party for two weeks."
 

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Native

ToungeInCheek since 2010
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5 Year Member
Social distancing video. Breakdown of exponential growth etc.

(Sorta like that compounding interest on those stocks that lost all their value. Talk about flattening the curve.)

 

Native

ToungeInCheek since 2010
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5 Year Member
So it is easy to get excited about potential therapies and drug options. People everywhere get excited about it. The President has given props. We’ve talked about it here.

Now read this thread and watch how dude slays the report. Time, replicates and controls are important.

 
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Native

ToungeInCheek since 2010
Staff member
5 Year Member
Q: If someone is treated with Chloroquine (if it is proven effectiv at helping fight the infection) will they build immunity or will the drug clear it before immunity can be established?

A: It is impossible to know the answer to that. Timing and length of exposure is an important part of developing immunity. This is doubly hard as it isn't known yet how strong of an immune response is going to develop. Given the variety of length of incubation times that are reported. (2-14 days) and then you add on at what point in therapy a drug is given, a situation where too many variables are in play to give a definitive answer. IF one could develop a strong immune response, I would think immunity at some level definitely would be achieved because any therapy wouldn't be immediate.

Note: chloroquine hype is real and the info about its success has likely been overstated it would seem to me. A lot of these questions get answered as data gets collected.
 
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