What makes the current coronavirus different from the others?

[TeethWhitener]

The Internet Book of Critical Care has a lot of good info for this thread:
https://emcrit.org/ibcc/covid19/
A few points relevant to the thread.
1) Novel Coronavirus phylogeny:
https://nextstrain.org/ncov
2) COVID-19 can directly induce ARDS via viral cytopathy:
https://www.thelancet.com/action/showPdf?pii=S2213-2600(20)30076-X

Edit: there is also some limited evidence that the Wuhan strain is significantly more virulent than the strain outside China.

 

[Ygggdrasil]

The article mentions "Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal Coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled. "

An article from the World Economic Forum states, "However, genomic comparisons suggest that the SARS-Cov-2 virus is the result of a recombination between two different viruses, meaning the exact origin of the virus is still unclear." From where would they get the notion?
https://www.weforum.org/agenda/2020...-analysis-covid19-data-science-bats-pangolins
Besides pangolins, the WEF article mentions bats (genus Rhinolophus, e.g., Rhinolophus affinis) and palm civet (Paguma larvata).

Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission
https://jvi.asm.org/content/84/7/3134

The WEF article ends "Two questions remain unanswered: in which organism did this recombination occur? (a bat, a pangolin or another species?) And above all, under what conditions did this recombination take place?"

Most of the SARS-CoV-2 genome resembles bat coronaviruses, expect for one protein encoded by the viral genome, the spike protein (which is the element that helps the virus bind to the host cells). The spike protein more closely resembles the spike protein from coronaviruses found in pangolins. Therefore, from this data, scientists infer that the SARS-CoV-2 virus resulted from recombination between a bat Coronavirus and a pangolin coronavirus. When and where this recombination took place remain yet to be understood.

Here are some preliminary, non-peer reviewed pre-prints that present genetic analysis of various Coronavirus sequences making the case that SARS-CoV-2 likely resulted from recombination of bat and pangolin coronaviruses:
https://www.biorxiv.org/content/10.1101/2020.02.07.939207v1
https://www.biorxiv.org/content/10.1101/2020.02.17.951335v1
https://www.biorxiv.org/content/10.1101/2020.02.13.945485v1

 

[Astronuc]

Therefore, from this data, scientists infer that the SARS-CoV-2 virus resulted from recombination between a bat Coronavirus and a pangolin coronavirus.

That's what I was thinking, but also, is it bat -> pangolin, or pangolin -> bat, or bat/pangolin -> human -> pangolin/bat. Is the recombination necessarily in the secondary or intermediate host?

Pagolins are from Malaya, and they are smuggled to China through Guangong, and then distributed to wet markets across China, but perhaps more in central China (?) to places like Wuhan, Hubei. Where would a pangolin encounter bats, in Malaya, Guangdong, or Wuhan, in the market?

And according to nextstrain.org/ncov, the virus is mutating in the human population as it spread from China to Europe and US, and between Europe and US.

 

[Ygggdrasil]

@PAllen it is kinda hard to get data from that country, like rates and such. All I have seen so far is Washington Post reports.

Germany has a low death rate, we are just now starting to test for it. Me and you could have had it already, and since the symptoms are mild we might have thought it was a "simple" cold. We weren't testing for it since we didn't have the equipment. It was cold and flu season and I'm willing to bet 0.0000001 Dogecoins that sometime during the winter you might have had a runny nose, chills, cough, or some difficulty breathing(in severe cases), all symptoms of the virus.

Inconsistencies in the data between different countries is telling me we should wait and see because data might be incomplete. If we all reported total deaths per month, keeping a running count, this would be more obvious.

I'm still skeptical, since we haven't reached anywhere near what the influenza does in the US alone https://www.cdc.gov/flu/about/burden/2017-2018.htm#table1

It is not bad that now we are all washing our hands after we go number 2, so some good might have come out of this after all.

Here's a good article with a counterpoint to your view: https://www.statnews.com/2020/03/18/we-know-enough-now-to-act-decisively-against-covid-19/

You're focusing too much on the death rate from the disease (which will definitely vary between locations due to how widespread testing is and due to readiness of health systems to take on an large influx of patients, see this article for a nice discussion). Essentially, we are already seeing in locations like Wuhan, Italy, and Washington State, where outbreaks have been very severe and have overwhelmed the local health care system (e.g. see this reporting from Italy). Under these conditions, death rates will increase because those with severe illness will not be able to get the proper treatment (e.g. due to lack of ICU beds or ventilators). This could be one reason why locations with severe outbreaks like Italy and Wuhan have reported death rates 5-10x higher than locations where the outbreak has not been so severe and the health care system is better prepared (e.g Germany and South Korea).

These problems can be compounded by shortages of protective equipment for nurses and doctors, which could lead to them getting sick or scared to go to work, further reducing hospitals' capacity to treat cases. An overwhelmed hospital system also increases mortality from non-coronavirus related deaths as hospitals would have reduced capacity to treat other emergencies (heart attacks, strokes, car accidents, apdendicitis, etc.).

As to why we have to take drastic actions now, even though the numbers are well below what we would see in a typical flu season. From the STAT News Op/Ed I cited above:

First, the number of severe cases — the product of these two unknowns — becomes fearsome in country after country if the infection is allowed to spread. In Italy, coffins of Covid-19 victims are accumulating in churches that have stopped holding funerals. In Wuhan, at the peak of the epidemic there, critical cases were so numerous that, if scaled up to the size of the U.S. population, they would have filled every intensive care bed in this country.

That is what happens when a community waits until crisis hits to try to slow transmission. Intensive care demand lags new infections by about three weeks because it takes that long for a newly infected person to get critically ill. So acting before the crisis hits — as was done in some Chinese cities outside Wuhan, and in some of the small towns in Northern Italy — is essential to prevent a health system overload.

Second, if we don’t apply control measures, the number of cases will keep going up exponentially beyond the already fearsome numbers we have seen. Scientists have estimated that the basic reproductive number of this virus is around 2. That means without control, case numbers will double, then quadruple, then be eight times as big, and so on, doubling with each “generation” of cases.

If we wait to stop the spread of infections until our healthcare capacity is even at 25% of its capacity to deal with new cases, a three week lag in new intensive care cases combined with a doubling time of 7-10 days means that, even if you could halt all new infections at that point, the number of cases are already on their way to becoming sever cases in the coming weeks is already enough to overwhelm the health care system.

 

[Ygggdrasil]

That's what I was thinking, but also, is it bat -> pangolin, or pangolin -> bat, or bat/pangolin -> human -> pangolin/bat. Is the recombination necessarily in the secondary or intermediate host?

Pagolins are from Malaya, and they are smuggled to China through Guangong, and then distributed to wet markets across China, but perhaps more in central China (?) to places like Wuhan, Hubei. Where would a pangolin encounter bats, in Malaya, Guangdong, or Wuhan, in the market?

Unsure. These questions likely require further study.

And according to nextstrain.org/ncov, the virus is mutating in the human population as it spread from China to Europe and US, and between Europe and US.

Edit: there is also some limited evidence that the Wuhan strain is significantly more virulent than the strain outside China.

@TeethWhitener do you have a source for the claim?

The only paper I've seen claiming two strains of the virus is from the journal National Science Review . This paper has been criticized by other researchers in the field:

An analysis of genetic data from the ongoing COVID-19 outbreak was recently published in the journal National Science Review by Tang et al. (2020) 84. Two of the key claims made by this paper appear to have been reached by misunderstanding and over-interpretation of the SARS-CoV-2 data, with an additional analysis suffering from methodological limitations. [...] Given these flaws, we believe that Tang et al. should retract their paper, as the claims made in it are clearly unfounded and risk spreading dangerous misinformation at a crucial time in the outbreak.

http://virological.org/t/response-to-on-the-origin-and-continuing-evolution-of-sars-cov-2/418

Observing mutations in the nextstrain data is expected. The real question is whether those mutations have any effect on the behavior of the virus, which can be difficult to determine just from the sequence data. Also, experts urge caution in interpreting sequencing data from the various viral isolates as sampling is quite sparse: https://www.sciencemag.org/news/202...-coronavirus-moves-they-re-easy-overinterpret

 

[Astronuc]

Does sampling method affect the sequencing tests? I ask this not as expert in the subject, but as one who has seen the preparation of metallography affect results leading to potential misinterpretation of surface characteristics (nanometer scale), e.g., grain boundaries of metal alloys with other phases.

 

[Ygggdrasil]

By sampling, I mean that relatively few viral isolates have been sequenced, which makes it difficult to build reliable phylogenetic trees that show the evolutionary relationship between viruses from different locations (similar to the problem in figuring out where the SARS-CoV-2 came from; if we had more sequences of bat and pangolin viruses, maybe we could observe a more direct ancestor to SARS-CoV-2 in bat, pangolin or another species that could tell us more about the origin of the virus).

 

[Astronuc]

By sampling, I mean that relatively few viral isolates have been sequenced, which makes it difficult to build reliable phylogenetic trees that show the evolutionary relationship between viruses from different locations (similar to the problem in figuring out where the SARS-CoV-2 came from; if we had more sequences of bat and pangolin viruses, maybe we could observe a more direct ancestor to SARS-CoV-2 in bat, pangolin or another species that could tell us more about the origin of the virus).

Yes, I saw that mentioned in the papers, that we do not have enough sequences from different species. The world has been unprepared probably because this was not considered a high priority, even though some scientists have been concerned for some time, and following previous outbreaks.

 

[TeethWhitener]

@TeethWhitener do you have a source for the claim?

I can’t recall; the Tang paper may well have been the source for that info. Thanks for pointing out the criticisms.

 

[sqljunkey]

I don't find the theory it is plugging up the healthcare situation very convincing either, according to this paper, https://www.sciencedirect.com/science/article/pii/S1201971219303285, about 20,000 people die over there too because of the flu, you still take these patients to the hospitals, ICUs etcetera. They had ample time over there to develop a remarkable healthcare system to cope with all the flu patients. I mean the numbers alone are crazy.

Or are you arguing somehow that the care cycle for a terminally ill patient that has the Covid is more intensive than the ones that have the influenza.

I don't find the theory that the Covid 19 could have been an ongoing epidemic before 2019 until someone in China isolated this novel virus, too outlandish. Given the rather mild symptoms and our very limited to non existent testing capabilities up to this point, it is possible.

All of a sudden the virus is everywhere, some of it cannot even be explained by travel or contact with traveling persons."The hospitals would have been plugged up with people trying to get in and out if the virus was present before 2019" is not a valid argument either.Until I get those death numbers(covid deaths + other deaths) and do some comparisons I won't know for sure...

I mean, seriously, they will eventually find a vaccine for the Covid that is as effective as the influenza vaccine, and we will all forget about it.

 

[BillTre]

Sometimes the first attempts to make a vaccine do not work out so well.
Its not a sure thing to be counted on.

 

[jim mcnamara]

I have stayed out of this because it seems political.

@sqljunkey However some points:
A vaccine may not be likely. Too many new Covid 19 serotypes have evolved. Herd immunity is probably not a viable opportunity. It is an RNA virus, you may want look up why that makes a difference.
https://jvi.asm.org/content/92/14/e01031-17
<edit fix typo 12:12 MDT>
Plus, I think you are confusing replacement mortality with excess mortality. Check Italy for what they are doing with the piles of caskets. If the mortality rate was net ~zero piles of caskets would not be a problem because the infrastructure would be there to handle them already.

You also may not be clear about why getting R₀ (transmission rate) well below 1 slows an epidemic. Estimates of Covid 19 R₀ are 2-3.5, lots higher higher than the flu.

BTW I am going to ask you to look up the number of people who died from the harmless(?) influenza problem of 1918. Flu is not a problem, right?

 

[PeterDonis]

the care cycle for a terminally ill patient that has the Covid is more intensive than the ones that have the influenza

My understanding is that ventilators are the scarce resource; a far smaller percentage of annual flu patients need them because the flu much more rarely causes respiratory distress than COVID-19 does. To the point where "shortness of breath" is listed as a symptom to watch for for COVID-19 but not for flu.

 

[snorkack]

You're focusing too much on the death rate from the disease (which will definitely vary between locations due to how widespread testing is and due to readiness of health systems to take on an large influx of patients, see this article for a nice discussion). Essentially, we are already seeing in locations like Wuhan, Italy, and Washington State, where outbreaks have been very severe and have overwhelmed the local health care system (e.g. see this reporting from Italy). Under these conditions, death rates will increase because those with severe illness will not be able to get the proper treatment (e.g. due to lack of ICU beds or ventilators). This could be one reason why locations with severe outbreaks like Italy and Wuhan have reported death rates 5-10x higher than locations where the outbreak has not been so severe and the health care system is better prepared (e.g Germany and South Korea).

One reason. And another reason is that testing gets overwhelmed so patients with mild cases do not get tested and identified (but keep spreading the infection).
Germany has another reason for low death rate. They test "for benefit of living"... meaning that people who die of Coronavirus at home without assistance do not get tested nor count into death rate,

 

[Motore]

Here in Slovenia we are testing only those who need hospitalization. There are several reasons:
1.) We are a small country and per capita our test numbers per day are still pretty high.
2.) Because of the incubation period is long, testing someone now can show negative result, even though he is infected (he would test positive in 4 days for example)
3.) Evereyone should act like he is already infected, which means work from home if possible or strictly follow social distancing rules.

This virus (as seen in Italy) can overhelm the health care system in 3 weeks. Even though the flu kills between 4 000 - 10000 people a year in Italy it is spread in space and time, which means it cannot overhelm the system as the new Coronavirus does. But the new Coronavirus is much more contagious, has cca 20-30x higher mortality rate, is localized and is hitting all at once. In three weeks the death tool in Italy is almost 5000!

If we don't follow the measures (social distancing, no gatherings, lockdowns, ...) the death toll could spike very very fast.

 

[jim mcnamara]

@mfb @jedishrfu

Re: vaccines
per https://nextstrain.org/ncov There are 880 reported genotypes (strains), this is a compendium of those genotypes.

As of
20-March-2020.

RNA viruses have high mutation rates.

This is the same reason why there are dozens of extant influenza genotypes, and we create trivalent (or quadrivalent) vaccines which work against a fraction of them. This is also the reason the flu shot in 2018 did not match very well and flu mortality was much higher. Mortality appears, based on current data, to be higher for Covid 19 than the last bad bout of flu in the US. So a vaccine miss puts us back behind the eight ball mortality-wise for either flu or nore so for Covid 19.

So what I am saying is the "vaccine" can be created and tested. But we are in a situation where a random happenstance we cannot control may and will render it less than perfect and and the "miss" will be far worse than most flu epidemics have ever been. Assuming the same clinical progression as we see now.

Or, how about:
The flu sucks and so does Covid 19. Neither is something we humans want in any, way, shape for form. Our vaccine approach needs to change. And simply saying 'a vaccine is coming' is not a true panacea.

 

[mfb]

If you check the virus in hundreds of people you can find hundreds of variants. Not surprising. Most mutations won't be relevant for a vaccine.
If you click on "clock" you can see that these strains differ by single mutations, or sometimes don't even differ at all but still count as separate strain.

 

[TeethWhitener]

I don't find the theory that the Covid 19 could have been an ongoing epidemic before 2019 until someone in China isolated this novel virus, too outlandish.

The low phylogenetic divergence makes it extremely unlikely that this virus has been circulating in humans for much longer than has already been observed.

 

[Ygggdrasil]

@mfb @jedishrfu

Re: vaccines
per https://nextstrain.org/ncov There are 880 reported genotypes (strains), this is a compendium of those genotypes.

As of
20-March-2020.

RNA viruses have high mutation rates.

This is the same reason why there are dozens of extant influenza genotypes, and we create trivalent (or quadrivalent) vaccines which work against a fraction of them. This is also the reason the flu shot in 2018 did not match very well and flu mortality was much higher. Mortality appears, based on current data, to be higher for Covid 19 than the last bad bout of flu in the US. So a vaccine miss puts us back behind the eight ball mortality-wise for either flu or nore so for Covid 19.

So what I am saying is the "vaccine" can be created and tested. But we are in a situation where a random happenstance we cannot control may and will render it less than perfect and and the "miss" will be far worse than most flu epidemics have ever been. Assuming the same clinical progression as we see now.

Or, how about:
The flu sucks and so does Covid 19. Neither is something we humans want in any, way, shape for form. Our vaccine approach needs to change. And simply saying 'a vaccine is coming' is not a true panacea.

I agree with @mfb here, the fact that we observe different genotypes have because the virus has accrued various mutations, does not mean that there are different strains of the virus. As an analogy, human individuals differ by ~20 million base pairs, but (as far as we know) all are equally susceptible to the Coronavirus (so to the virus, there is only one strain of human). Only very specific mutations could allow a human to be immune from the virus (e.g. in the case of HIV), and likewise, only very specific mutations in the SARS-CoV-2 virus would allow it to evade immunity in vaccinated individuals.

Thus, many mutations will not have any effect on the virus, and we would mainly care about mutations that affect the behavior of the virus. So far, we have not seem much meaningful change to the viral genome:

Since the start of the pandemic, the virus hasn’t changed in any obviously important ways. It’s mutating in the way that all viruses do. But of the 100-plus mutations that have been documented, none has risen to dominance, which suggests that none is especially important. “The virus has been remarkably stable given how much transmission we’ve seen,” says Lisa Gralinski of the University of North Carolina. “That makes sense, because there’s no evolutionary pressure on the virus to transmit better. It’s doing a great job of spreading around the world right now.”

There’s one possible exception. A few SARS-CoV-2 viruses that were isolated from Singaporean COVID-19 patients are missing a stretch of genes that also disappeared from SARS-classic during the late stages of its epidemic. This change was thought to make the original virus less virulent, but it’s far too early to know whether the same applies to the new one.

https://www.theatlantic.com/science/archive/2020/03/biography-new-coronavirus/608338/
(note: this article from the Atlantic is a great, popular press summary of what we know about how the virus differs from other coronaviruses, and how those differences may lead to its success in spreading across the globe).

Now, that is not to say that the virus won't or cannot mutate to evade immunity. These types of mutations are certainly possible, and people are monitoring virus sequences to monitor for that possibility. Because the immune system recognizes the protein on the surface of the virus (the spike protein), it is very important to monitor changes to the spike protein as these types of mutations do carry the possibility of altering how our immune system recognizes the virus.

 

[jim mcnamara]

@Ygggdrasil Yes But.

You are correct that it does not mandate genetic change that impacts the clinical aspects of vaccination. It just starets off with a big disadvantage.

This is a nice textbook example of R selection - with genetic drift and mutation at work in populations with little selection pressure. A sort of free-range virus sortie.

There are four main branches on the phylogenetic tree per GISAID data sets as of right now. (link below) Instead of wild ducks like influenza has, this virus has 7+ billion humans to facilitate genetic drift and mutation.

See R & K Selection for a definition: https://en.wikipedia.org/wiki/R/K_selection_theory

A virus with 'a whole new world' to itself, is a model of R selected activity for what we are seeing. This virus population is going to rapidly diverge genetically. Based on the GISSAID data. As you know RNA viruses mutate rapidly. There exist four primary branches now.

This is a wonderful resource using GISAID data sets, please play around with it.
https://nextstrain.org/ncov
This is a discussion of genetic drift and mutation in R & K selected populations of Eukaryotes (birds)
https://royalsocietypublishing.org/doi/full/10.1098/rspb.2015.2411

As of this writing there are 946 genome samples in the chart. I am not claiming anything "wierder" than what we see in influenza genomes over the course of a year, just that the magnitude of rate of change not like flu. Humans are the "wild duck populations like the flu has" in this model. We speed up the change by losing the intermediate steps that flu has to go through.

Such that vaccine expectations are misplaced, IMO. For a vaccine to be effective in 6 months when trials begin, and will continue later to work in the wild on virus populations that have changed. A lot. This will result in misses like we have had in the past two years with flu vaccines. A vaccine miss here is and order of magnitude worse than for the flu given the current virulence and infection transmission data.

It is not that we cannot make vaccines it is how well they work over time.

Plus, SARS patients apparently lose immunity after 1+ years. Assuming that same limited immunity obtains here: This translates to a somewhat limited duration herd immunity.

FWIW I really object to the concept 'but it is like the flu'. This denigrates a horrible disease (flu) which we should have been able to get a handle on by now. We have simply slowed it down. Example: 2018 was a bad flu year in part, due to a vaccine/antigen mismatch.

This in turn speaks negatively to getting a vaccine handle on a more transmissable and virulent disease via vaccines. Antivirals may really be a better choice.

This link shows that we can isolate very early new flu outbreaks with TamiFlu rings. And we do not do it proactively and widely. At least there are no reports other than this one on H1N1 in Singapore 2009.
https://www.nejm.org/doi/full/10.1056/NEJMoa0908482

It has been successfully used in nursing homes:
https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1532-5415.2002.50153.x

For Covid 19 -- Even if we come come up with an anti-viral that works as well as TamiFlu, we will then need to proactively contain it with rings. Or give out billions of pills every year. Or as an alternative, try to keep a series of vaccines current for all forms. And re-vaccinate as needed. We can do it. Somewhat. But the way it was referenced in the posts that triggered this discussion was not correct, IMO. It is not like the flu.

 

[Laroxe]

This reports on a study that seems to have galvanized the UK and US governments, not surprising really considering the picture it paints.
Currently the case figures are unreliable, the rate of testing is very different in different countries and this makes it impossible to get an accurate estimate of mortality. It seems as if stressing the risk to the elderly might have been a bit of a mistake, a significant number of younger people become seriously ill and the facilities needed to treat these people will likely be overwhelmed in most countries, this will impact on the mortality rate.
I don't thing that the way in which death is attributed to corvid19 is a major problem, the illness seems to run a fairly characteristic course, the pneumonia is usually as a result of the virus rather than a secondary bacterial infection and may be associated with a "cytokine storm" like that seen in SARS.
There have been some drugs that have shown promise but so far none can be recommended but trials are going on everywhere, Meplazumab is a monoclonal antibody and like all of the new biologics will be horribly expensive, its unlikely that it could be used outside of very specific situations in wealthy countries.
Even if infection only produces weak immunity there may be some hope in the new vaccine technology that instructs the bodies own tissues to produce the antigens, this would probably produce an extended exposure and a better immune response.
I suspect that the study reported may be biased towards a worst case situation, we still have very limited information really, but its easy to see why things are changing so quickly.
https://www.ft.com/content/16764a22...1W0zHgVCcFBjkCOa9VWzQ0WfWVFGDcvbKhjoZwRb8rxNo

 

[Ygggdrasil]

I don't find the theory it is plugging up the healthcare situation very convincing either, according to this paper, https://www.sciencedirect.com/science/article/pii/S1201971219303285, about 20,000 people die over there too because of the flu, you still take these patients to the hospitals, ICUs etcetera. They had ample time over there to develop a remarkable healthcare system to cope with all the flu patients. I mean the numbers alone are crazy.

Comparing annual deaths to influenza across the whole country versus the number of COVID-19 deaths over the course of a small amount of time at an early stage of the epidemic is misleading. Current figures from Italy show over 500 deaths per day, which is 10x higher than the estimated number of influenza deaths per day (~55 deaths per day based on 20,000 deaths per year). Furthermore, these deaths are concentrated in certain regions of the country, so the burden on hospitals in these regions is even 10x higher than the normal burden from influenza. Given that it takes about 2-3 weeks for an infection to lead to a death and the number of deaths per day keeps increasing, we are likely to see things get worse (>10x the burden on hospitals than influenza).

 

[Astronuc]

Most of the SARS-CoV-2 genome resembles bat coronaviruses, expect for one protein encoded by the viral genome, the spike protein (which is the element that helps the virus bind to the host cells). The spike protein more closely resembles the spike protein from coronaviruses found in pangolins. Therefore, from this data, scientists infer that the SARS-CoV-2 virus resulted from recombination between a bat Coronavirus and a pangolin coronavirus. When and where this recombination took place remain yet to be understood.

Here are some preliminary, non-peer reviewed pre-prints that present genetic analysis of various Coronavirus sequences making the case that SARS-CoV-2 likely resulted from recombination of bat and pangolin coronaviruses:
https://www.biorxiv.org/content/10.1101/2020.02.07.939207v1
https://www.biorxiv.org/content/10.1101/2020.02.17.951335v1
https://www.biorxiv.org/content/10.1101/2020.02.13.945485v1

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30251-8/fulltext

Findings
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.

 

[Laroxe]

Flu really doesn't seem to be a good model for understanding possible vaccines for covid19. The influenza viruses have made something of a fetish of changing their surface antigens and this can involve several different processes. The viruses can change due to antigenic drift, antigenic shift and the change driven by the selective pressures of the new host. Antigenic drift reflects changes that can occur due to random mutations that occur during replication, while these are common, particularly in RNA viruses the specific mutations needed to effect the surface antigens are not. This means that influenza type B and C and now apparently covid19 tend not to undergo major changes, so far Covid 19 seems to be remarkably stable.

The same can not be said of influenza type A which appears rather less choosy about its hosts, a virus can jump from one species to another and does so fairly frequently. There are a number of variables that influence the likelihood of cross species transmission perhaps the most important being the degree of exposure of a weakened host. It is also possible for type A viruses from two different species to infect the same intermediate host and even the same cell, this can lead to anew subtype with a mix of surface antigens from both (or more) of the infecting viruses. This leads to a major reorganisation of the surface antigens and its this that causes the problems in developing effective vaccines. Viruses are then subject to the selective pressures of the host and the requirement to optimize the effects it has on the host to improve its own fitness.

We now have the technology to identify potential surface antigens from the genetic code and use a variety of methods to expose an individual to a number of these, the choice appears particularly important in Covid 19 as the effectiveness of the antibodies varies a great deal and some may facilitate an abnormal response the so called cytokine storm. However targeting several different surface antigens makes it difficult for the virus to adapt and avoid the effects. Interestingly its only now that these technologies are being used in flu vaccines and one is already undergoing trails that specifically targets the antigens shared by most strains. These appears to offer broad protection against flu, but the most recent technologies remain unproven.

When considering the effects on health resources covid19 is not offered as an alternative to flu, the flu is still circulating and continues to cause illness. Generally the serious illness caused by flu can be treated and the seriously ill that recover tend to use critical care facilities for shorter periods of time. Up to 20% of Covid 19 infections result in hospitalisation with around 6% requiring intensive care often over several weeks. I thought you might be interested in all of the treatments and vaccines being studied. Currently the most promising is the use of hyper-immune gamma globulin from the blood of people who have recovered, this will become more available as the pandemic develops but doesn't really represent a treatment for the majority. Sorry for rambling.

https://milkeninstitute.org/sites/default/files/2020-03/Covid19 Tracker 032020v3-posting.pdf

 

[Phil Core]

All kinds of interesting stuff here but does not directly address original questions

Upfront it must be acknowledged that the CoronVirus is a single strand RNA virus that reverse transcribes.

Have heard that an upper bound is 32,000 nucleotides.

1. " Ability to make new viruses - apparently 1000 times more prolific than flu." Where is this number of 1000 times coming from? Actually I think it is related to 3 - "If I remember this right, its "spike proteins" cling more strongly to the cell membrane." But how scientific is using 1000 times?

It was noted by Chinese researchers that the the CoronVirus is distinguishable from other very similar RNA viruses by nucleotide coding at the end of the RNA chain. Not sure if the coding is for a protein or ? My understanding was that whatever this appendage was it made it easier for the virus to penetrate cellular integrity. How convenient to have a protein that does this. Of interest is that this novelty appears at the end of the RNA chain. To me meaning newer.

2. "Unlike flu viruses, it does not appear to mutate because it has a "proofreading enzyme" that repairs mistakes in replication of its RNA. " Does anyone know with RNA how this might work? I always thought proofreading was a DNA to RNA function. I originally suspected that if it was an RNA virus it would be more amendable to mutation.

 

[TeethWhitener]

Upfront it must be acknowledged that the CoronVirus is a single strand RNA virus that reverse transcribes.

Coronaviruses do not reverse transcribe.

 

[TeethWhitener]

Unlike flu viruses, it does not appear to mutate because it has a "proofreading enzyme" that repairs mistakes in replication of its RNA. " Does anyone know with RNA how this might work?

The error checking is provided by an exoribonuclease. Here’s one paper from a while back:
https://pubmed.ncbi.nlm.nih.gov/23966862/

 

[TeethWhitener]

Only tangentially related to the thread, but quite related to my last post:
https://pubmed.ncbi.nlm.nih.gov/29511076/
Apparently, as of a few years ago, remdesivir was being evaluated for its potency against SARS-CoV, as it interferes with the exoribonuclease and its proofreading activity. Furthermore, mutations in the exoribonuclease that confer resistance to remdesivir are also associated with loss of fitness in SARS-CoV.

 

[Phil Core]

My bad on the reverse transcription. That has to do with the way the virus is tested for. Still do not know why you need to reverse transcribe to detect the virus.

https://www.vox.com/2020/3/20/21188266/coronavirus-test-us-united-states

The most commonly used test is a nasopharyngeal swab, where a special Q-tip is put up your nose to take a sample. This swab is then sent out to a laboratory that can extract the virus’s RNA. The virus that causes Covid-19, SARS-CoV-2, is an RNA virus, which means it uses ribonucleic acid as its genetic material. It requires a process called reverse transcription, or RT, to transcribe its RNA into DNA.Because there’s not very much material in one sample, a polymerase chain reaction (PCR) is used to rapidly make billions of copies so it can be analyzed. The DNA is dyed a fluorescent color, which glows if SARS-CoV-2 is present. Most of the available Covid-19 tests use this process. The virus has about 32,000 nucleotides, so there’s a variety of tests, each looking for different parts of the virus’s genome, and they use different chemicals — there’s not one test every country is using.

 

[TeethWhitener]

Still do not know why you need to reverse transcribe to detect the virus.

Google RT-PCR. It’s the gold standard technique for COVID testing right now.

Edit: your post is strange. You ask and then answer your own question. Are you still not sure why PCR requires reverse transcription?

 

[Phil Core]

Most of what you are quoting is over my head.

But

1. I always thought the continuity of genetic information was a function of the double helix. Wrong in one, correct in the other.

I am a strong advocate of incremental analysis. So how does this correction function work? Having only 1 strain makes it hard for me to imagine. Is it the biochemistry that does not work or is there a master blueprint that must be adhered to?

2. As far as testing. Why can you not directly test for the RNA in a cell? The way I understand it you have to take the RNA - reverse transcribe - and then make millions, billions of copies. Seems very inefficient.

 

[TeethWhitener]

1. I always thought the continuity of genetic information was a function of the double helix. Wrong in one, correct in the other.

I am a strong advocate of incremental analysis. So how does this correction function work? Having only 1 strain makes it hard for me to imagine. Is it the biochemistry that does not work or is there a master blueprint that must be adhered to?

I’m not sure what any of this means.

Why can you not directly test for the RNA in a cell? The way I understand it you have to take the RNA - reverse transcribe - and then make millions, billions of copies. Seems very inefficient.

It’s a lot easier to detect billions of something than one of something.

 

[BillTre]

PCR, the basic technique involved here, only works on DNA, not RNA.
You have to turn the RNA sequence into DNA sequence in order to PCR it.
Being able to do PCR opens a lot of doors for you analytically, that could not be done with RNA.

If you are unsatisfied with that, you might want to develop a RNA based PCR-like method yourself.

 

[Phil Core]

I’m not sure what any of this means.

Others are saying that this virus is not a good candidate for mutation. Somehow it self corrects. How is this done?

Although I never fully appreciated it, I imagined that with a double helix, if there was a problem with one strand in some way it might check the other to see if there was a more efficient method available.

How is a single strain RNA being self corrected? Has to be a lot of something in the chain to do that.

 

[Phil Core]

PCR, the basic technique involved here, only works on DNA, not RNA.
You have to turn the RNA sequence into DNA sequence in order to PCR it.
Being able to do PCR opens a lot of doors for you analytically, that could not be done with RNA.

If you are unsatisfied with that, you might want to develop a RNA based PCR-like method yourself.

I guess I could develop my own test but I would not want to deprive someone else of the adventure.

I am unfamiliar with PCR. However, RNA DNA both composed of nucleotides.

Is there something that makes the CoronVirus unique? Yes. Apparently it is the ending sequence. Search for that.