The Biology and Immunology Corner

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Coronavirus: Robots use light beams to zap hospital viruses - BBC News UV roombas to sterilise rooms. I remain unconvinced as to their coverage for horizontal surfaces.



On the news last night UK PM was trying to hint that an antibody test kit was almost ready to roll. Something that was rapidly backpedalled by the science advisor. But for those versed with the art how rapidly can these be made? Secondary question, do they help?
 
Don't know if this has been brought up yet but as all other viruses vaccines are periodically adjusted for in terms of mutation, how likely is it this one could mutate into a deadlier one before a vaccine is made, thus rendering a promising vaccine useless? What are the chances of it getting stronger rather than weaker?

I asked a similar question a while ago on a different thread and got an answer from Sean. Here's his answer...

You're correct, the virus SARS-CoV-2 (which causes the disease COVID-19) is a single positive stranded RNA betacoronavirus. In generality, single stranded RNA (ssRNA) is less "stable" than double stranded DNA (dsDNA). As such, ssRNA genomes are often much shorter and more prone to mutation compared to larger dsDNA viruses. For example, HIV-1 (a ssRNA retrovirus) mutates so quickly that each infected person usually has dozens and dozens of unique sequence isolates in their body at any time. As you suggested, this means it can mutate around the many drugs we have invented and has prevented us from making a functional vaccine.

However, SARS-CoV-2 does not appear to mutate that quickly. In fact, of the hundreds of sequences that have been gathered to date, VERY few point mutations exist. Furthermore, betacoronaviruses have some of the longest ssRNA viral genomes. Together, this suggests that the "mutational sequence space" available must be limited. In other words, in contrast to HIV-1, SARS-CoV-2 is able to replicate with much higher fidelity, most likely because its own RNA polymerase is very very efficient. So, in terms of treatment/vaccine, this may help us. If it is slowly mutating, then our vaccines will be less likely to fail. HOWEVER, I promise you that it will mutate in the future; that is an inevitability.

The longer answer is that it very much depends on how the vaccine works. For a hundred years, the way vaccines were made was to deactivate or weaken a virus and give it to a person. This allowed the immune system to do what it does best; sample the virus and develop a semi-permanent resistance to infection without the burden of actually getting sick.

However, viruses often have evolved ways to "hide" from the immune system. For example, influenza mutates rapidly which why there are a near infinite number of versions. But a big reason why vaccines are only partly effective is because the immune system often targets the easiest part of the virus to target. The virus leaves this "low hanging fruit" while assuring that it mutates this part of its genome the most rapidly which leaving the parts that can't mutate "protected".

But we are getting smarter. Instead of just weakening viruses and letting the immune system figure it out, we are trying to take the guesswork out of the equation by telling the immune system what to target. I don't know the specifics, but Melissa Moore's team is working towards this concept as well. So I would argue that it is more likely that the vaccine strategies developed for SARS-CoV-2 (if they work) will likely permanently effective for SARS-CoV-2. But they probably won't be effective for the inevitable SARS-CoV-3/4/5/... But as we get better and better at identifying, isolating, and rapidly sequencing, we will also get better and better at developing treatments and vaccines as fast as the virus mutates.
 
Coronavirus: Robots use light beams to zap hospital viruses - BBC News UV roombas to sterilise rooms. I remain unconvinced as to their coverage for horizontal surfaces.



On the news last night UK PM was trying to hint that an antibody test kit was almost ready to roll. Something that was rapidly backpedalled by the science advisor. But for those versed with the art how rapidly can these be made? Secondary question, do they help?

If what was meant is a virus test that works via antibodies, then that's good news, although I question the relevance. For years, our best way of detecting a pathogen was to use pre-made antibodies (usually mouse or rabbit, sometimes horse and donkey etc). The assay to look up on google would be called an ELISA. Basically, you coat a plate with the antibody, then put on samples. You also have a signal antibody as well, and if you get a positive signal, that means the antibody was able to bind meaning the pathogen (or at least its proteins) were there.

But I was talking to a few colleagues who have the same opinion as mine. The current testing procedure relies on nucleic acid detection via PCR. That is a heck of a lot more sensitive that an ELISA and I can't imagine that the antibody would be cheap. So I'm not quite sure why it would be considered particularly helpful in testing unless it was used a some sort of clinical validation.

As for how fast they can be made, we are getting faster and faster at developing antibodies for clinical development and research. Waaaayy back in the 80s, 90s, and 2000's, all we could do was pump an animal full of antigen (the purified proteins of the virus) and wait for the animals immune system to make an antibody. Then, we would bleed the animal (or dialyze) to extract the antibody from the blood. Now we have the ability to isolate the specific B cells that make the antibody, sequence the exact gene region, and put that gene into other, in vitro systems to make the antibody large scale in culture without having to bleed 500 horses dry. So a process that tooks years then took months and now we can do it in a few weeks to a month. So they are on schedule I guess.
 
Coronavirus: Robots use light beams to zap hospital viruses - BBC News UV roombas to sterilise rooms. I remain unconvinced as to their coverage for horizontal surfaces.



On the news last night UK PM was trying to hint that an antibody test kit was almost ready to roll. Something that was rapidly backpedalled by the science advisor. But for those versed with the art how rapidly can these be made? Secondary question, do they help?

Actually, a better use of antibodies under mass production would be as a therapeutic, not a test. If a person is sick with the virus, it is possible to give them an antibody specific to the viral proteins before their own body has had the chance to figure an antibody for itself. This is the "convalescent serum" that was given to the white people in the Ebola outbreak. Basically, isolated human blood serum of people infected and cured of Ebola containing the antibodies they made when they were sick. Although, now, we can sequence the B cells specifically make it in a tissue culture lab without having to bleed people. Science!!!
 
I think what he meant was a test to find out who had been infected and recovered and now had 'some' immune response who could be allowed out! Measuring the herd immunity so to speak.


Latest analysis in uk suggests 0.5-1% fatality for those infected still which is not good numbers.
 
I think what he meant was a test to find out who had been infected and recovered and now had 'some' immune response who could be allowed out! Measuring the herd immunity so to speak.


Latest analysis in uk suggests 0.5-1% fatality for those infected still which is not good numbers.

Oh ok, that's a bit different. Those assays are important and are how we determine whether blood at blood banks may or may not be contaminated. So, basically, these assays are the reverse of what I said before. We have purified antigen (proteins) from the virus that we test against a person's blood. If you have a positive signal, then it is because their blood contained an antibody against the viral protein suggesting that they were infected and have now developed a protective immune response against it. It's a good idea, but they tend to be a bit loose on accuracy and sensitivity. Better than nothing I guess.

Theoretically those assays can be developed quickly. But the testing to determine whether they are accurate and sensitive is the slow part. Which is probably why the science helper dude downplayed it.
 
I have to agree in that I also believe the mortality rate wont necessarily stay low (ish)

I'm a little worried that we (UK) havent been slightly more draconian in our mitigation efforts - folks just aren't heeding the government's request to stay in, away from crowds, pubs etc.

Meanwhile, my partner has a cough and it isnt continuous, no fever, so I am a bit lost whether I should be calling in work and isolating for 14 days, for fear of jumping too quickly and taking time off that I may need later
 
Oh ok, that's a bit different. Those assays are important and are how we determine whether blood at blood banks may or may not be contaminated. So, basically, these assays are the reverse of what I said before. We have purified antigen (proteins) from the virus that we test against a person's blood. If you have a positive signal, then it is because their blood contained an antibody against the viral protein suggesting that they were infected and have now developed a protective immune response against it. It's a good idea, but they tend to be a bit loose on accuracy and sensitivity. Better than nothing I guess.

Theoretically those assays can be developed quickly. But the testing to determine whether they are accurate and sensitive is the slow part. Which is probably why the science helper dude downplayed it.

Haha, coming from a cancer diagnostics perspective, I have a massive love/hate relationship with antibodies, especially when you park a fluorescent label on them (steric inhibitions). I had actually started typing up a pretty decent post getting into "if you want to move a bit quicker we're finding nanobodies to be more promising, but you have to have the experience with them to benefit," but you hit the specificity/sensitivity part pretty well (and the subsequent near-infinite time finding the right antibodies with the most favorable kinetics).

I have been thinking we do need a decent titer test for SARS-COV-2, if for no reason than get confirmed-immune folks back to work and have as much of our economy/infrastructure remain active. I'm sure efforts are in place to do just that.
 
I have to agree in that I also believe the mortality rate wont necessarily stay low (ish)

I'm a little worried that we (UK) havent been slightly more draconian in our mitigation efforts - folks just aren't heeding the government's request to stay in, away from crowds, pubs etc.

Meanwhile, my partner has a cough and it isnt continuous, no fever, so I am a bit lost whether I should be calling in work and isolating for 14 days, for fear of jumping too quickly and taking time off that I may need later
Your thinking seems a little ambiguous? You think government should be more draconian but you are thinking of going to work?
 
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Sean, is there a way to determine if you've had C19 and are now recovered from the symptoms? If you've had it, can it mutate quickly enough that you may catch it again? Also, if you have recovered from it, are you now safe to mingle among others or could you catch it again and pass it on to others?
TIA.

It is unlikely that you can catch it twice. I can't read the article, but I am extremely skeptical. Most likely, it is just an effect of the PCR test being very sensitive and her own immune system acting slowly.
 
That is how Italy started out but when they ran out of hospital beds in general and ICUs in particular their fatality rate rose to a bit over 8%.

This is not correct. The apparent mortality rose when they stopped testing people with weak or no symptoms. Also Italy did not run out of hospital beds just yet. ICUs are critically occupied locally in the Lombardy region, but again this can't explain the fatality rate as it is a very recent development.
 
I don't know about epidemiologists' last days models, but here a usefull advice of Chinese Red Cross Vice President Sun Shuopeng who claim we MUST freeze things deeper in order to make the crisis shorter, a little as some here alerted before for Americas which had few days more to react. Maybe all the worlds should react even more is perhaps the talk in the link ?


It is talking about Italy but seems it's a worldwild advice to avoid bounce, boomerang effect the most and keep alive the medical system whom help us. Not saying research need time and some important things as food, electricity, good news from the family for them too.


Synchronicity between countries seems necessary to avoid the boomerang effect with airports, turism, business and family travels... between places and countries.



Italy Coronavirus Lockdown 'Not Enough,' Says China, Healthcare Staff Stop Counting Bodies
worths a read.
 
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