Covid-19 now exists in two forms, indicating it's already mutated at least once | Hacker News Reader

Covid-19 now exists in two forms, indicating it's already mutated at least once

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197 pointsbookofjoe78 comments

There's some pretty sharp criticism of this paper on the r/COVID19 subreddit (which is the one where the scientists hang out):

https://www.reddit.com/r/COVID19/comments/fdsltf/about_the_l...

Basically, there are 111 different mutations, not 2, and it's misleading to point to a single point mutation and set that as the arbitrary division point between strains while ignoring the other 110 mutations that have been catalogued. There is currently not enough evidence for the researcher's claims that this particular mutation causes observable differences in the virus's reproduction or virulence characteristics that the other mutations do not.

Here's the substance of the criticism written up:

http://virological.org/t/response-to-on-the-origin-and-conti...

"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). 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."

What about whether or not you can "catch it again" once your immune system has beaten one version?

Antibody diversity is created through a process called hypervariation. It is basically a random generation process. We then filter out those that recognize markers produced by our own body. So each person's antibody will work differently in recognizing the virus, that is choosing what markers to bind to. Whatever antibody that works will go through a clonal multiplication that causes the B cells that produced the antibodies to replicate, conferring resistance to reinfection. So long as your choice of antibody does not happen to depend on the SNP (a seemingly small chance but we also don't know its function for the virus so hard to say) you will be resistant to both types.

How come folks are saying you can get reinfected tho? Has there ever been a disease that the same strain can reinfect someone? Wouldn’t that imply they’d never recover?

Some diseases have 2 phases (biphasic), so you get sick, recover somewhat, get sick again, often with different symptoms.

I've read in the press that corona virus might be biphasic, which is a big problem for an air-borne transmissable disease. In the jet age, quarantining potentially thousands or millions of passengers becomes expensive and disruptive when there's a week between phases.

Lyme disease is like that. First you get a bullseye rash and flu-like symtoms, it goes away, then later your organs are attacked.

https://en.wikipedia.org/wiki/Biphasic_disease

That's different than a chronic disease, where you never recover.

Why can’t the memory cells help for the second phase?

Shouldn’t the first phase act as a sort of vaccine?

I wonder if it's possible that the virus can take shelter in cells that are not exposed to the antibodies. Don't herpes viruses do something like that? People get chicken pox as a kid, and later get shingles.

I think there have been a few unverified reports of people catching the virus again. However these might be caused by false negative tests (viral load being lower during the time of testing), then they re-take the test when they have a higher viral load(?) and it comes back positive.

This is purely based on other comments I've read, I personally know nothing about viruses.

The exact same way that people repeatedly catch the common coronavirus year after year. 2019's novel coronavirus is destined to end up being known as the "common cold" or coronavirus with time. All common colds are a coronavirus and newly discovered ones are novel. IOW there is no vaccine in the pipeline because there's never been a vaccine for the common cold.

https://www.who.int/health-topics/coronavirus

> All common colds are a coronavirus and newly discovered ones are novel.

Technically not true - coronaviruses cause 15-30% of common colds. The most common cause of the common cold is rhinovirus (30-80%); coronavirus is next, followed by influenza (10-15%), adenovirus, and then other viruses like RSV. The rest of your comment is fairly likely IMHO, though.

But you’re talking about mutations or other strains. My question is can the exact same virus reinfect a person?

I’d think you’d never clear it to begin with if that was the case.

Just to be clarify, B cells undergo somatic hypermutation while undergoing expansion after antigen recognition. On re-exposure, memory cells will be available to identify existing antigens and re-expand the B cells involved with attacking the viral particles.

Immune system is amazing. It can actually detect different strains of the same virus, even if it has never seen that specific mutation. https://www.sciencedaily.com/releases/2018/04/180430212353.h...

> "After exposure to one strain of virus, these memory cells are then better able to recognise variants of the virus if they encounter them in the future. The immune system learns to protect against a whole group of related viruses, not just the one it experienced."

This is kind of a double edged sword though.

Say the virus mutates so that only 50% of its features are recognizable.

You'd think that the fact that your cells can recognize this is good, and it is to some extent, but, it also prevents new cells from learning about the virus(in efforts to prevent autoimmunity in analogous scenarios with non malicious objects; our immune system has to walk the fine line between being too permissive and allowing infections, and being too restrictive and murdering its own host through nasty autoimmune diseases).

So, it mounts a 50% response, which is often good enough, and more than makes up for the more limited response with speed.

But what happens when the % recognizable drops to like 3%? Some percentage of cells will recognize the 3%, and be able to mount a weak response, but more critically, block other cells from developing new responses. This limited response will slow down a proper response and itself will be likely ineffective.

Its known as "original antigenic sin", if you want to read more.

I hope COVID-19 isn't reading this.

I'm pretty sure covid-19 doesn't read Hacker News.

Not that surprising, since an immune system would be very likely to encounter a slight mutation or "variant" of the virus in the future, after the virus spread through others in the population.

But this obviously isn't the case with seasonal viruses such as influenza or coronavirus.

Unknown at this time. It doesn't follow that a specific mutation would mean that your immune system would fail to recognize a different strain. Antibodies don't work like that - just look at how the smallpox vaccine was done through inoculation with cowpox, a completely different disease. Scientists would need to study a cohort of people with known immunity to one strain of COVID-19 and see if they can get it again with exposure to a different strain.

It's also unknown whether it's possible to develop immunity to COVID-19 at all, with reports of reinfection in both China and Japan.

Maybe I'm misunderstanding something about the immune system, but that doesn't seem possible. How can you eliminate a viral infection without developing immunity to the virus causing it - aren't they both the same underlying process?

if the virus is particularily good at shifting the code that corresponds to Epitopic Regions of its antigens, namely those found on the spike protien of the virus then its in an arms race with the immune system.

> which is the one where the scientists hang out

Thanks for that. There are a lot of subreddits popping up and I've been trying to distinguish between the legit ones and the cryptoprepper ones.

If there are 111 different mutations, does that mean that a common vaccine is highly improbable/impossible?

Not at all.

The effectiveness of a vaccine is related to the effectiveness of the bodies immune response to the virus.

As long as different mutations do not affect the effectiveness of a given immune response provided for by a vaccine, that vaccine will be effective against those mutations.

Mutations can affect many aspects of a disease, and often this means a different level of effectiveness of an immune response, but it really does depend on the specific mutation.

For now, there are no selection pressures on different strains from vaccines; it will be interesting to see what mutations become prevalent once testing of vaccines starts.

Why does it take so long to develop a deactivated vaccine version of the virus to teach our immune system what to attack?

Safety. You have to understand what 'deactivated' means for this virus, and that people won't get significantly sick if you feed it to them. That takes time.

While this is not exactly a direct answer to your question, these pages may be helpful:

https://shotofprevention.com/2018/03/14/how-flu-strains-are-...

https://www.cdc.gov/flu/about/viruses/change.htm

The key part of the summary to me is this:

Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure.

It's too early to really know for sure, but one thing that often happens with viruses is that over time, the less fatal versions spread more effectively. It might be that the L type is the more lethal type which killed so many people in Wuhan, and the S type is the more silent type that is spreading around the world with a lower mortality rate.

Probably just wishful thinking on my part, but it's interesting to be aware of the possibility.

> L type is the more lethal type and the S type is the more silent type

Well that's easy to remember, L=lethal and S=silent. But I imagine there is a prosaic explanation for the haplotype naming. Anyone know what the L and S stand for? Googling hasn't turned up anything for me.

> It might be that the L type is the more lethal type which killed so many people in Wuhan, and the S type is the more silent type that is spreading around the world with a lower mortality rate.

I suspect this is the main reason we're seeing divergences in different countries, with South Korea getting the "good" type and Italy getting the bad one.

> but one thing that often happens with viruses is that over time, the less fatal versions spread more effectively

The key here is selection pressure more than time, with no controls in place there's no selection pressure until it runs out of hosts, until then it's highly successful and does not need to adapt. In this case we've added some artificial selection pressure.

If there are places with only the bad type of the virus I wonder if we could ethically introduce the good type? On one hand your saving overall lives but you'd be purposefully infecting people with something that potentially has life long effects.

I think it has to do with the number of hospital beds per capita. South Korea has over 12 per 1000 but Italy only has 3.1. That is probably making a huge difference.

The US only has 2.8 per thousand which is horrifying, I hope the Italy situation doesn’t happen here.

Wow, how are those numbers so different? You would think a functioning health care system in any developed country would be similar. The controversial topic in the US isn't really the quality or quantity of healthcare, it's about who pays for it.

You might tell me it's because of something unique and bad in the US system, and we should see the Scandinavian countries to see how it should be done - but no, Denmark 2.6, Canada 2.5, Sweden 2.2 all have fewer beds per capita than the US. It's Japan and Korea who are the outliers at the top at 12 and 13. [0]

It really must be a cultural/lifestyle thing. Would I really spend 4 times as much of my life in a hospital bed if I lived in Korea? And if so, would that really be a good thing? I assume usage is reasonably high in both, the beds don't sit empty waiting for a pandemic.

Or you might remind me that those countries have famously old populations. But that's not it either. Japan has an old population, but still only twice as many 70+ as the USA (according to the population pyramids at [1]). And Korea has the same proportion as the US.

It makes me wonder if they are comparing like with like: maybe some of the reported hospital beds in Korea would be considered to be in nursing homes or convalescence centres in Europe or the US.

[0] https://en.wikipedia.org/wiki/List_of_OECD_countries_by_hosp...

[1] https://www.populationpyramid.net/republic-of-korea/2020/

It is indeed very strange that Korea and Japan should have 400% more hospital beds per capita than the U.S., Canada, or Scandanavia. I tried to dig into the OECD methodology[0] to see if they mentioned anything noteworthy, but nothing grabbed my attention. Their notes about the U.S.[1] and Korea[2] seem pretty similar. I'm wondering if in Japan and Korea, people stay in hospitals for longer periods for the same condition than in the U.S. For example, in the U.S. mothers giving birth would stay in the hospital for a week or more in 1950s from what I heard, but these days they are discharged after a couple days. What's a typical stay for uncomplicated childbirth in Japan and Korea? If it's a week or 10 days, then that would give a possible datapoint for having many more beds.

[0] https://stats.oecd.org/index.aspx?DataSetCode=HEALTH_REAC

[1] Notes about the United States: Coverage: AHA-registered hospitals in the United States. U.S. hospitals located outside the United States are excluded. Includes all the AHA registered hospital beds for all types of hospitals. Estimates are for all AHA registered hospitals. AHA-registered hospitals include facilities such as short-term general, psychiatric hospitals, wards, rehabilitation institutes, maternity homes, tuberculosis hospitals, leprosariums and alcoholic treatment institutions. Estimates exclude U.S. associated areas such as Puerto Rico and AHA non-registered hospitals.

[1] Notes about the Korea: Coverage: Hospitals: all sorts of medical institutions equipped with wards of at least 30 beds. Excludes day-care beds, emergency beds, surgical tables, recovery trolleys, delivery beds and cots for normal neonates.

The methodology sounds quite similar, indeed.

Maybe the stays are just longer. In Ireland we've seen the same trend in maternity hospitals: mother and baby used to stay for a week, now a couple of days. But I thought that was just best practice now and keeping them longer doesn't improve health outcomes.

It is already happening in the US, and the countermeasures being taken are totally inadequate. Please do everything you can to avoid infecting yourself and others.

> If there are places with only the bad type of the virus I wonder if we could ethically introduce the good type?

You're presuming that infection with the good type confers immunity to the bad type. So far as I know, that is not yet proven.

I don’t think Korea has a less lethal strain, they’re just testing a lot of people and capturing more mild cases.

Also, thanks to the stupid cult church being the hotbed of infection, the population graph of patients is skewed toward young people: ~30% of all known patients in South Korea are in their 20s, which would lower average mortality rate.

What does stupid cult church mean here?

A large majority of the cases in South Korea are linked to Shincheonji, an organization that calls itself a Christian church but believes the Bible is a secret message to its founder.

I find this to be highly compelling. The “fatality rate” is the number of deaths divided by the number of known cases.

There are several very significant variables which determine the number of known cases, but the upper bound is the number of people tested.

Take for example in WA where the number of cases is ~40 and 10 deaths. The total number of tests last week was some number of hundreds.

With a virus which can be extremely mild in the vast majority of cases and where a test costs thousands of dollars, it is reasonable to expect the total number of cases could be vastly understated.

The WHO has been reporting ~1% of cases are asymptomatic, this has it's own caveats because it comes after China's lock down but there's little reason to believe there a huge numbers of unknown cases out there, at least in countries testing well.

> With a virus which can be extremely mild in the vast majority of cases

I haven't seen a breakdown of how many get what the "mild" symptoms, but anything not requiring hospitalization including pneumonia are considered mild. Many of these mild cases would at least be going to their doctor to get a week off work.

Edit - found a break down: https://www.who.int/docs/default-source/coronaviruse/who-chi...

> As of 20 February 2020 and 12based on 55924 laboratory confirmed cases, typical signs and symptomsinclude:fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), myalgiaor arthralgia (14.8%), chills(11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%), diarrhea (3.7%), and hemoptysis (0.9%), and conjunctival congestiion (0.8%).

Those symptoms are worthy of a doctor visit and skipping work.

> The WHO has been reporting ~1% of cases are asymptomatic, this has it's own caveats because it comes after China's lock down but there's little reason to believe there a huge numbers of unknown cases out there, at least in countries testing well.

Unfortunately, the United States is currently a country that is not testing well.

Knowing 1% of reported cases are asymptomatic doesn’t tell us anything about what percent of asymptomatic cases are unreported. Only way to know what is testing with random sampling from the asymptomatic general population.

> Only way to know what is testing with random sampling from the asymptomatic general population.

They did. They tested a lot of people in contact with infected people (so even more likely to be an asymptomatic carrier than the general population) and their findings from the link above is:

> Asymptomatic infection has been reported, but the majority of the relatively rare cases who are asymptomatic on the date of identification/report went on to develop disease. The proportion of truly asymptomatic infections is unclear but appears to be relatively rare and does not appear to be a major driver of transmission.

Given the evidence the onus is proof is now on anyone claiming there are large amounts (of course there will always be some) of undetected cases.

I am not talking about entirely asymptomatic cases, which I believe are fairly rare. I am talking about mild cases which could be easily mistaken for a common cold, which is the most common presentation.

I think what you may be missing is that 100,000 people in WA could have gone to their doctor last week with “a cold” and they wouldn’t have been tested for COVID, because the FDA would not allow state labs to run the tests and the CDC refused to run it on mild cases.

I use the example of WA because it’s glaringly obvious that a lack of testing has resulted in a significant number of cases going undetected over the last couple weeks in that area.

The old CDC guidelines only allowed severe cases to be tested, so the only confirmed COVID cases were severe. Resulting in a “fatality rate” that was pushing 10%.

So it’s just an example of how this number is inflated by lack of testing. I believe a similar situation is playing out in Italy.

By comparison, South Korea has an extremely robust testing regime (free drive through testing stations, over 100,000 tested, capacity of over 10,000 per day) [1] and has identified 6,284 cases and has seen 40 deaths with currently 52 in serious condition. That puts their “known case fatality rate” at 0.6%-1.5%.

Simply put, the “known case fatality rate” can only possibly overstate the actual fatality rate, unless you believe there are deaths due to COVID happening that are being misattributed. This is obviously an entirely different category of error than not testing someone with a mild cold.

It’s useful to take what we know about “known case fatality rate” in heavily-tested populations and we can use this to estimate how many undetected cases are present in the population in under-testing locales. E.g. 10 COVID deaths would point to the likelihood of over 1,000 actual cases of COVID in the community. This of course assumes similar demographics and standards of care, which may not be the case.

[1] - https://www.ctvnews.ca/health/south-korea-takes-fast-food-ap...

~90% of cases get a fever which is uncommon for a cold so if there were large amounts of people with the disease it would at least be showing as a huge spike of people with the flu, plus we'd likely see a spike in deaths. It won't be mistaken for just a cold. The way it's playing out in Italy is that there were a lot of diagnosed cases early on but once the testing caught up they seem to be on the same exponential curve as everywhere else, but this was only high in percentage terms and low in raw numbers.

There is definitely under reporting of cases (and some misdiagnosed deaths), but so far no reason to think it's a tip of an iceberg type of scenario and there are large masses of undiagnosed people. For calculating mortaility rates there's also the lag time between getting the virus and death to take into consideration.

Going back to your original post about the fatality rate in WA, the numbers are simply too low to indicate anything at all. There are only 4 countries on Earth we can get much statistical significance from and of those Iran is the only one that lacks testing at the moment.

You make a very good point that a high fever is uncommon with a cold, and so at that point people would be thinking they perhaps have the flu and, depending on the culture and health care system, could decide to go get a flu test.

Once that’s negative you would expect maybe a COVID test would be done, again, depending on the health care system, availability of testing, and perhaps the financial impact.

If the average time of infection to death is 18 days and the doubling time is 5 days, 10 deaths today would indicate at a 2% mortality rate:

500 infections 18 days ago.

~6800 infections today in the community.

This is an interesting simulation, but keep in mind you are extrapolating both backwards by 50x and then, from there, also forwards with an aggressive exponential multiplier, all starting with a very low n.

So there are an enormous number of variables which can cause reality to diverge. Each on of those 10 deaths have a unique situation which lead to that point.

For example, if they are all related to the same cluster (and I believe they are), and that cluster is an elderly demographic which doesn’t get outside much, then the R0 will be significantly lower than 10 totally unrelated business people traveling for work, or who might feel pressure to go into their offices despite feeling a bit feverish... totally different profiles and potential impact.

>where a test costs thousands of dollars

Is this true?

I imagine US insurance companies could make this true if it's not

I'm not understanding how there could be "no selection pressure" for a virus. Since human bodies vary and infection is a complex process, it seems to me there's always selection pressure. And especially given that this appears to have recently made the jump from another species [1], there's no reason to think that the virus was somehow perfectly adapted to all of humanity.

[1] https://www.cdc.gov/coronavirus/2019-nCoV/summary.html#ancho...

I think we’re confounding two parts of evolution.

Random mutation, and it’s sibling non-random cumulative natural selection (selection pressure).

I guess it on what one defines as a selection pressure.

> If there are places with only the bad type of the virus I wonder if we could ethically introduce the good type? On one hand your saving overall lives but you'd be purposefully infecting people with something that potentially has life long effects.

Nah-- there's no way to know the tradeoff in lives lost, etc.

The "good" news is, versions that cause less acute sickness and death are going to be better at escaping quarantines and controls.

If we can reduce the lethality to near zero levels, we'll call it a vaccine.

Covid-19 is the name of the disease. The virus is called SARS-Cov-2.

The virus has mutated plenty of times already and exists in many forms not just two. The paper talks about being able to group existing mutations into two types. Within each type the genomes share more common elements than differences.

The disease differs too though, the mutations are not inert, and they have a measurable effect on the severity of the complications.

the disease does differ greatly already within a subtype, the same subtype may cause severe or mild effects - the response is primarily host-related, not virus related

Says the WHO.

Go look at https://nextstrain.org/ncov if you want to see all of the mutation paths! Wonderful site/org with contributors doing great work around the globe sending in sequences.

A critique of this paper by some scottish virologists: http://virological.org/t/response-to-on-the-origin-and-conti...

https://bedford.io/blog/ncov-cryptic-transmission/ - For anyone looking for more info around how the transmission/mutation works. Quick read.

Can we please correct the title? This is in reference to the virus SARS-Cov-2. Covid-19 is the name of the disease.

To back your claim: "The disease caused by infection with SARS-CoV-2 is now called COVID-19."

Source:https://www.worldaware.com/resources/intelligence-alerts/sar...

Detailed rebuttal: https://docs.google.com/document/d/1niBInt7tgQ57iihgenPFMyn7...

tl;dr this paper should be retracted

Why does it take so long to develop a deactivated vaccine version of the virus to teach our immune system what to attack?

What was interesting about this, that is contrary to common understanding of virology and pandemics, is that there as a mutation that significantly increased the virulence of one strain of SARS-CoV-2. Over time, viruses will become less virulent as they continue to infect new hosts.

They used the word "aggressiveness", which does not necessarily associate with "virulence". As they are only looking at frequency data at the genomic level it is everyone's guess on how the distribution is achieved. I take it to mean shorter incubation time so that it spreads faster but also more easily impacted through infection control measures.

> It is also unclear whether the L type is more virulent than the S type

You're right. I finally got a chance to read the study fully, but was basing my comments from the r/COVID-19 thread.

Genes do what genes do. Nothing here is unexpected, surely? But, if the lethality drops and becomes sustaining in the population, we're still net-worse-off overall compared to not having had this virus. Its just 'choose the least-worst outcome' time.

I think at this point, public health initiatives are aimed at moving the shape of the curve, not the final trajectory of the virus. It's going to spread everywhere but if it does so more slowly the health system will not be overloaded by point-explosions of calls on staff and equipment.

I feel for the Tasmanian toilet-paper workers who will work overtime to meet a panic-demand, and then be unemployed with a mountain of un-wanted rolls, as we consume the 6 month supply we bought in a frenzy.

One of the problem is naming. What is the difference of all these names? The L and the S type are they the one found in patient. Why stress non-recomb...

And all those mainland chinese academics ... sorry but CSB we trust them.

Ah, those untrustworthy Chinese academics who are calling for the controversial action of... more comprehensive followup studies.

That is controversial in some circles:

"Academic journal editors were banning unqualified FRIN statements as early as 1990"

https://en.wikipedia.org/wiki/Further_research_is_needed

Remainder of sentence:

", requiring more specific information such as what types of research were needed, and what questions they ought to address."

Article:

> Further studies investigating how the different alleles of SARS-CoV-2 viruses compete with each other will be of significant value.

> If these changes are not due to sequencing errors, it would be interesting to test whether and how these mutations affect the transmission and pathogenesis of SARS-CoV-2.

> Thus, it will be interesting to investigate the function of the S84L AA change in ORF8, as well as the combinatory effect of these two mutations in SARS-CoV-2 pathogenesis.

> follow-up analyses of a larger set of data are needed to have a better understanding of the evolution and epidemiology of SARS-CoV-2. There is a strong need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with SARS-CoV-2.

I'm not sure if I would call those unqualified statements. Some are a bit vague, but they do identify questions that should be addressed and that a larger dataset is required.

I was being mildly facetious.

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