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Medicine Science

Evidence Builds That an Early Mutation Made the Pandemic Harder to Stop (nytimes.com) 176

As the coronavirus swept across the world, it picked up random alterations to its genetic sequence. Like meaningless typos in a script, most of those mutations made no difference in how the virus behaved. But one mutation near the beginning of the pandemic did make a difference, multiple new findings suggest, helping the virus spread more easily from person to person and making the pandemic harder to stop. From a report: The mutation, known as 614G, was first spotted in eastern China in January and then spread quickly throughout Europe and New York City. Within months, the variant took over much of the world, displacing other variants. For months, scientists have been fiercely debating why. Researchers at Los Alamos National Laboratory argued in May that the variant had probably evolved the ability to infect people more efficiently. Many were skeptical, arguing that the variant may have been simply lucky, appearing more often by chance in large epidemics, like Northern Italy's, that seeded outbreaks elsewhere.

But a host of new research -- including close genetic analysis of outbreaks and lab work with hamsters and human lung tissue -- has supported the view that the mutated virus did in fact have a distinct advantage, infecting people more easily than the original variant detected in Wuhan, China. There is no evidence that a coronavirus with the 614G mutation causes more severe symptoms, kills more people or complicates the development of vaccines. Nor do the findings change the reality that places that quickly and aggressively enacted lockdowns and encouraged measures like social distancing and masks have fared far better than the those that did not. But the subtle change in the virus's genome appears to have had a big ripple effect, said David Engelthaler, a geneticist at the Translational Genomics Research Institute in Arizona. "When all is said and done, it could be that this mutation is what made the pandemic," he said.

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Evidence Builds That an Early Mutation Made the Pandemic Harder to Stop

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  • Herd Mentality (Score:5, Insightful)

    by EETech1 ( 1179269 ) on Thursday November 26, 2020 @02:39PM (#60768406)

    That is the huuuge problem with letting this virus spread uncontrolled..

    By the time we think we have this under control, covid-19, or more likely covid-21, will show us just how crafty it can be given a few hundred million more opportunities to fine tune it's attack against the human body, and our attempts at a vaccine.

    • Re:Herd Mentality (Score:5, Interesting)

      by AleRunner ( 4556245 ) on Thursday November 26, 2020 @02:58PM (#60768442)

      That is the huuuge problem with letting this virus spread uncontrolled..

      By the time we think we have this under control, covid-19, or more likely covid-21, will show us just how crafty it can be given a few hundred million more opportunities to fine tune it's attack against the human body, and our attempts at a vaccine.

      This, big time. The virus is kind of trapped in a local maximum of effectiveness where it seems not to be able to mutate much. It probably needs several simultaneous genetic changes to get out of that maximum to a different one. The number of mutations available will be more or less directly related to the number of hosts available to the virus. Each host gives the virus billions of opportunities to find a new set of mutations that change it. Each new set of hosts also gives the virus more chances to hop over into a non-human host, mutate more (that species will have a different local maxima) and then hop back, changed like the Minke virus. A vaccine resistant mutation would be a nightmare, especially because it could would remain hidden for months. Even after the vaccine is available, we may still end up having to cut the world into two, the infected and uninfected parts with strict quarantine for travel between the two like the current entry to New Zealand.

      • Low mutation rate. (Score:5, Informative)

        by DrYak ( 748999 ) on Thursday November 26, 2020 @04:30PM (#60768714) Homepage

        This, big time. The virus is kind of trapped in a local maximum of effectiveness where it seems not to be able to mutate much.

        Not exactly. It's mostly not mutating much because coronavirus family happen to have an ExoN at nsp14 - i.e.: they have the ability to proof read the RNA copies that RdRp makes.
        In simple terms: it doesn't make as many mistakes when copying as other RNA viruses because it's able to fix quite a lot of the mistakes.
        SARS-CoV-2 isn't much different from other member of that family.

        Compare this with influenza which not only makes mistakes but even has a segmented genome making it easier to mix'n'match multiple bits.

        The end result is that my colleagues who study its phylogenetic observe a 1:4 slower mutation rate compared to influenza.

        Each new set of hosts also gives the virus more chances to hop over into a non-human host, mutate more (that species will have a different local maxima) and then hop back, changed like the Minke virus.

        The variant that infects mink has a couple of difference from the base variant at best.
        It has a slight difference in the Spike's poket which increase its chance to also bind to the ACE2 of some small mammals like mink.
        That's about it.

        Yes, we scientist do track the changes, because we can build "family trees" (phylogenetic analysis) which gives us valuable information about where the virus is travelling.
        But these changes as so small (we're litterally speaking about a couple of dozens of base pairs difference accross a 30k long genome. Most of which don't even translate into differences on the final protein), that the virus nearly always function the same.
        The result on the caracteristics of the virus are barely altered.

        In a petri dish TFA's D614G has a slightly better chance at entering cells and infecting them, and the "mink" variant [twitter.com](*) has a couple of substitutions that gives it the ability to bind to mink's cells (the deletion has no impact, it's just handy to track the variants).

        It's academically interesting, but most of the mutation have barely any impact on the pandemic.

        A vaccine resistant mutation would be a nightmare,

        Not much likely to happen fast:
        even influenza needs at least 1 year to come up with a new variant that is different enough, so that the previous antibodies don't work anymore.
        And sars-cov-2 mutates at even a slower pace. You're probably good to go with the current vaccine for at least 4 years.

        Take the example of the mutations mentionned above: at best that mutated spike will evade antibody that your lymphocytes would have produced against the exact spot ("epitope") where that mutation is. Any antibody that target virtually any other part of Spike will still see exactly the same target and will still work all the same.
        Definitely not big troubles.

        especially because it could would remain hidden for months.

        SARS-CoV-2 doesn't remain hidden for months due to mutations.
        It remains hidden, because it's completely assymptomatic in a surprisingly large number of cases (very approximately ~20%, as far as I remember from conferences), a further large number of case only have very little symptoms and don't realise they have COVID-19 or are patient that haven't started showing symptoms yet and don't know yet they have COVID-19 for several days.

        All these cause people to get on with their life completely unaware that they are actually secretly spreading the virus.

        But given a good decent testing policy in a country and contact-tracing resources, those people are going to be detected eventually.
        And with a semi-decent sequencing effort, any new variant of the Spike protein is going to be observed quickly.

        Also, with goot widespread application of measures (avoiding close proximity to avoid breathing each other's viruses, widespread masks so

        • will be a problem though.

          If an effective vaccine is developed, and widely deployed, then Covid-19 will be almost extinct, and have very little feed stock to mutate with.

          But if millions of people cannot or refuse to take it and remain infected then we can expect new strains every 4 years or so, requiring new vaccines in an endless cycle. Annoying.

          • by dryeo ( 100693 )

            There's still the animal reservoir, it'll keep hanging around in populations like mink waiting.

          • by ghoul ( 157158 )
            Good for Moderna stock. The promise of mRNA vaccines is that its pretty simple to create a new one as soon as the virus mutates.
        • Thank you for your informative reply, that's what I was waiting for!

          Happy Thanksgiving :-)

        • First, thanks for an informative reply.

          This, big time. The virus is kind of trapped in a local maximum of effectiveness where it seems not to be able to mutate much.

          Not exactly. It's mostly not mutating much because coronavirus family happen to have an ExoN at nsp14 - i.e.: they have the ability to proof read the RNA copies that RdRp makes.
          In simple terms: it doesn't make as many mistakes when copying as other RNA viruses because it's able to fix quite a lot of the mistakes.
          SARS-CoV-2 isn't much different from other member of that family.

          Funnily enough I just posted about this [slashdot.org] - but I don't know a really good explanation of the proof reading mechanism and what errors it can correct. Do you have something more you can point to to learn more about this?

          Compare this with influenza which not only makes mistakes but even has a segmented genome making it easier to mix'n'match multiple bits.

          The end result is that my colleagues who study its phylogenetic observe a 1:4 slower mutation rate compared to influenza.

          What will be the effect of having more copies of the virus out there? My understanding is that the number of mutated variants out there will increase almost linearly with the number of infected hosts and so, even though the virus changes at only 1/4 of t

          • Funnily enough I just posted about this [slashdot.org] - but I don't know a really good explanation of the proof reading mechanism and what errors it can correct. Do you have something more you can point to to learn more about this?

            I put a few keywords in that thread. But I mostly learned in the biology books in the first year medecine a decade ago. So beginning of university level books would contain the global information about the process.

            What will be the effect of having more copies of the virus out there? My understanding is that the number of mutated variants out there will increase almost linearly with the number of infected hosts and so, even though the virus changes at only 1/4 of the rate, given that there are massively more covid infections than flu infections, the number of genetic variants being tried will be more than with flu. Although it will still take longer to come up with a variant with multiple changes, given enough time there's more likelihood that more genetic variants will be tried including ones which have a better fitness than the current one.

            It would probably be true in theory, but you're missing a key point in your reflexions:
            Most of the epidemics in recent historical times are zoonosis: initially animal viruses which occasionally jump species (e.g.: bird flu, studies about prevalence of antibodies against bat coronavirus in farmers

        • It has a slight difference in the Spike's poket which increase its chance to also bind to the ACE2 of some small mammals like mink.

          So even if we go to the trouble of eliminating it from humans, it will tunnel into the groundhog population and live forever, like bubonic plague in the US?

          • So even if we go to the trouble of eliminating it from humans, it will tunnel into the groundhog population and live forever, like bubonic plague in the US?

            I see what you dug, here :-D

            Jokes (and puns) aside, that is actually (in more broad gerenal terms) already the current situation.

            We have already successfully wiped out some human specific diseases, e.g.: smallpox.
            But erradicating disease which have vast animal reservoir is going to be a much more complex task.

            That's the reason why all the recent epidemics outbreaks have been zoonosis (think Ebola, SARS, MERS, Swine flu, etc.)

            And the various members of the coronovirus family have big reservoir of bats into w

        • Thanks. I browse at +5 filter typically and yours is the only one that deserves that. The rest of +5 comments are utter generic propaganda bullshit regurgitated by online zombies and modded up by online zombies.

          Thanks for interesting info on self-fixing....

          It remains hidden, because it's completely assymptomatic in a surprisingly large number of cases (very approximately ~20%, as far as I remember from conferences),

          The difference between asymptomatic and resistant is viral load exerted every breath they ta

          • I still have to see studies that measure the viral load exerted by asymptomatics.

            Sorry, I would have way to many conference papers to shift through to find the correct reference.
            But by now we start to have a good chunk of signs that the asymptomatic do excrete viruses.

            Basically, the current understanding is that severity of symptoms are orthogonal to actual infection process:
            all undergo the infection, all have SARS-CoV-2 multiplying in them, all are excreting viral particles.
            (e.g.: On the CT scans, you will see small patches of "ground glass", i.e.: region of viral replication even they

    • by dryeo ( 100693 )

      Most pandemics have ended with the viruses mutating away. Look at the Spanish flu.
      https://www.bbc.com/future/art... [bbc.com]

  • Hogwash (Score:2, Insightful)

    What made this bad was a combination of people being contagious for days before showing symptoms, or being asymptomatic carriers. It doesn't do much good to screen for symptoms to control spread when contagious people aren't showing any. All of the world's Containment Protocols are based on diseases like Ebola where you can rule out the healthy without having to run lab tests.
    • Re:Hogwash (Score:5, Insightful)

      by satanicat ( 239025 ) on Thursday November 26, 2020 @02:52PM (#60768434)

      Well that, and either the feeling of entitlement or perhaps people just becoming more complacent since the state of things is starting to become more normal.

      Like here we were doing amazingly. zero cases for months, and then just last week we now have more than 100 cases in our province, all stemming from just a couple of people who felt it was less of an issue, decided to travel, return and not self isolate.

      100 cases doesn't sound like a lot, but it's a 100 more than nothing just a few days ago. So while we've enjoyed relative normal life, like no restrictions except wearing masks in public places; and no large groups of people in public; all the restrictions are coming back.

      I guess my point is, whether people like it or not, the restrictions authorities are trying to enforce actually do work, but only if they are actually followed. The sad thing is though, that it doesn't take a large portion of people to really mess things up for everybody, and it doesn't take very long either.

      • Taiwan hasn't had a case in over 200 days and New Zealand is completely free of the virus. The rest of the world is laughing at 'Murica. Trump's administration has more Covid cases now than some countries with millions of people.

        • Taiwan hasn't had a case in over 200 days and New Zealand is completely free of the virus.

          Huh? Taiwan reported two new cases today, with 63 cases currently active. New Zealand reported seven new cases today, with 66 cases currently active.

        • New Zealand is not completely free of the virus.

          7 new cases in the last 24 hours (all from overseas sources)
          66 currently active cases, of which 3 are from internal infection

          Not hundreds of thousands, however at the cost of over doubling the nations external debt SO FAR, and its still spinning upwards.
          Removing ALL external tourism, which earnt the country 1/3 of its foreign income previously.
          And strong lockdowns at the smallest signs of community infections - they just ha their largest unemployment increase

      • by mark-t ( 151149 )

        I think it's less than an issue that people are becoming more complacent in general and more that *some* people are not taking this situation as seriously as they should.

        Your example is a good one. 100 new cases all stemming from just a couple of people who didn't take the self-isolation requirements after travelling seriously. In my jurisdiction, if they had been caught breaking the restrictions on people travelling from elsewhere and been caught not self-isolating, they would have been fined.

        But t

        • by dryeo ( 100693 )

          You can still run into the issue of people who feel they have to go to work, even if they do feel somewhat sick. The pandemic fatigue is also a real problem. At the beginning almost everyone was following the health orders, now not so much.

          • by mark-t ( 151149 )

            You can still run into the issue of people who feel they have to go to work, even if they do feel somewhat sick.

            Is that still happening in places? I thought that this pandemic woke up employers to the reality that they need to have reasonable paid time off policies for people who could otherwise bring a contagious disease into work.

            At the beginning almost everyone was following the health orders, now not so much.

            Almost everyone still *is* following public health orders, actually. At least where I live.

      • They coined a term for it. Quarantine Fatigue. Its easy to be vigilant for a brief time. Its like locking your shit up at night. You have to get it right every single time. The criminal has to get lucky just one time. This time its the virus being lucky, but the rationale stands. Letting your guard down from time to time will do it. I have a bad feeling about thanksgiving. The biggest problem is people let their guard down for family. This isnt a conscious decision to infect you. Your family is more likely

        • by dryeo ( 100693 )

          Yea, Thanksgiving seems to have been a big part of the second wave here in Canada (Thanksgiving was last month here)

    • Hogwash. What made this bad was a combination of people being contagious for days before showing symptoms, or being asymptomatic carriers.

      Why can't the two things both be true?

      • by mark-t ( 151149 )
        Both *were* true.... But for any given case of contagion from an unknown source, it would be either one or the other.
    • This mutation is old news. However it is significant because it made it significantly more contagious than the wuhan strain. Remember that in Jan and Feb the WHO and CDC were in the no-mask mindset. They thought 6ft alone was enough. This mutation made the smallest amounts of exposure get a foothold. Unfortunately the information being disseminated through march described mild flu-like symptoms for most people. However here in the US, a lot of people describe something a bit worse than the flu.

    • I'll post this again [mit.edu]; it's worth a shot to see if it can be trained to differentially select [reddit.com] audio signatures in respiratory ailments in general. After all, it's just looking at audio waveforms along with other entered data; who knows what it could correlate between slight changes to the auditory response in the lungs and upper respiratory tract, perhaps based on an audio profile of some coughs, deep breaths, and maybe a few sung notes.

      Submit a sample yourself [mit.edu] and tell your friends to tell everyone else to

    • by gtall ( 79522 )

      Only some proportion of people have the virus with no symptoms. Another proportion do have both. Your argument is stupid.

    • by hAckz0r ( 989977 )

      From the very first sign of covid symptoms (for those not asymptomatic) you can just count backwards 2.4 days, on average, to when that person would have first started being infectious. But the tests that are currently available are not given, or sought by individuals, until you already have symptoms. That test doesn't likely give results right away and will undoubtedly miss this very critical window even in the *best possible circumstances*. Unless and until you can test everyone, once per day, and have i

  • If you had one version and it mutated could you catch the second mutation and become sick again? I canâ(TM)t find sufficient evidence in any direction and why I donâ(TM)t want to leave my house. I experienced recurring symptoms from feb through July (every 2-3 weeks a cough came back until about the time the mutation made it to my area then I was knocked out of commission for 2 months; I feel almost fully recovered with only a few long haul symptoms remaining)

    • > If you had one version and it mutated could you catch the second mutation and become sick again?

      Very unlikely. This is one specific change in one specific protein that the virus expresses. Your body will make antibodies to several proteins on the virus, normally.

      There's a very remote chance that your body made antibodies to only the S strain, or K strain, whichever you had, but that's so unlikely that the odds are far better that your memory-B cells failed to hyperdifferentiate and you didn't acquire

    • The short answer is probably not from a single point mutation. The virus would still largely look the same to the immune system (that's why catching related strains in some virus families confers at least partial immunity to other strains of the virus; ie. cowpox conferring some immunity to smallpox).

    • If you had one version and it mutated could you catch the second mutation and become sick again?

      Influenza and the common cold have been doing this for years.

      Coronaviruses are no different.

      • If you had one version and it mutated could you catch the second mutation and become sick again?

        Influenza and the common cold have been doing this for years.

        Coronaviruses are no different.

        The rates of mutation for different viruses are different and different families of viruses have completely different rates. HIV mutates many times in one single person. Rhinoviruses (most common colds) seem to mutate fast enough to get a few variants each year. Coronaviruses are mostly more stable than those and SARS-COV-2 seems to be reasonably stable generally - Coronaviruses have some error elimination mechanism [nih.gov] which I understand is part of this (any experts able to comment??).

        So Coronaviruses are d

        • The rates of mutation for different viruses are different and different families of viruses have completely different rates.

          This, absolutely.

          HIV mutates many times in one single person.

          (BTW: it's also a chronic disease which spans multiple years, giving much more opportunity for the virus to mutate and diversify inside a single patient.
          DISCLAIMER: The bioinformatics tool [github.io] we work on was spawn out of the need to analyse this diversity in cohort of HIV patients).

          Rhinoviruses (most common colds) seem to mutate fast enough to get a few variants each year.

          (BTW: In addition to the mutation rate problem that you right fully bring up as an important cause, another phenomenon that contributes to the annual reccurence of some common colds is that they might not generate a

      • by gtall ( 79522 )

        Not true. SARS-CoV-2 has the ability to fix mutations so some get weeded out. Yer bog standard corona virus that causes the flu does not, hence mutations cause new strains just about every year.

    • If you had one version and it mutated could you catch the second mutation and become sick again?

      Purely in theory: yes.
      In fact that's how some other viruses do it (most notorious example being Influenza).

      But for that to happen, you need the virus to accumulate enough mutations on the parts that sticks out and which are targetted by the antibodies, to the point that the new variant isn't recognisable anymore by any of the antibodies you have made.
      (And even then, your immune system is actually able to fine-tine some old antibody that kind-of half-work because the differences aren't that greate and it can

  • by jeti ( 105266 ) on Thursday November 26, 2020 @03:04PM (#60768462)
    Remember how Chinese scientists initially claimed that it's unclear whether human to human transmission is possible? And how China has been relentlessly attacked for downplaying the severity of the threat? And how the WHO has been attacked and defunded for cooperating with China?

    Maybe they weren't acting in bad faith.
    • Re: (Score:3, Interesting)

      by Entrope ( 68843 )

      No, they were definitely acting in bad faith. Taiwan and others publicly stated that there was human-to-human transition long before mainland China admitted it. The chance of this kind of mutation without human-to-human transmission is astronomically small, comparable to China announcing tomorrow that Chiang Kai-shek was a great guy after all and the CCP was wrong all along.

    • Remember how Chinese scientists initially claimed that it's unclear whether human to human transmission is possible
      That is not a claim, that is a statement of a fact.
      Which part of "it was unclear at that time" do you not get?

      • Remember how Chinese scientists initially claimed that it's unclear whether human to human transmission is possible
        That is not a claim, that is a statement of a fact.
        Which part of "it was unclear at that time" do you not get?

        Well, the part of "at that time", frankly. What time exactly was this supposed to be?

        To be clear... The virus didn't start in China, travelled briefly to Italy just to mutate there, then decided to go back home, and then spread throughout Wuhan and all of China. It did start in Wuhan and from there travelled throughout China and had then gone around the world.

        I do admire the self-reflection and the notion of there being possibly a false accusation, but we do know from fact that it did spread from human to h

        • At the time when China reacted and the first news came out: no one knew about cases outside of China,

          So your complete accusation is wrong from start to end.

          but we do know from fact that it did spread from human to human
          We know it now, but did not "precisely know" it then. But our parent keeps claiming: China knew it and lied. Which makes no sense at all.

          And if europ/america would pay more attention to what is going on, we would have expected that there is a "plague" coming to us, and not waited until we hav

    • Wasn't it always ridiculous to assume that human to human transmission is impossible? That would mean that every single infected person had gotten it from a bat (or similar animal).

    • If they weren't acting in bad faith, then how come in February you could not so much as ride a bike out of Wuhan to the next city, but you could take a flight to London, New York, Paris, Tokyo, Rome, or anywhere else in the world you wanted?

      Millions did, and the intention is pretty clear. We're scared, it's going to be rough, and if we're going to suffer then the whole world should burn too.

  • Italy (Score:5, Interesting)

    by bill_mcgonigle ( 4333 ) * on Thursday November 26, 2020 @03:18PM (#60768514) Homepage Journal

    This is just additional confirmation of what people on the ground learned in late Winter in Italy. The D614G mutation signaled the change from the S- strain to the K- strain, which ravaged Italy.

    For some reason many shoe factories in Northern Italy had no labor and the owners found they could run weekly flights to Wuhan to get laborers to run the factories and get good labor at a low cost. So there was a continual flow of people back and forth and by bad luck, the infectious person who came to Italy had the K-strain, so Italy got smacked hard when Wuhan hadn't had it as bad, because S- was majority in Wuhan and K- was majority in Italy.

    Americans vacationing in Italy brought K- back to NY and then violated quarantine. Boom.

    • Re:Italy (Score:4, Interesting)

      by Dixie_Flatline ( 5077 ) <vincent.jan.goh@NoSPam.gmail.com> on Thursday November 26, 2020 @04:39PM (#60768738) Homepage

      I wonder how this all lines up with the data that COVID may have been present in Italy and Europe before it became a pandemic, based on evidence from the waste-water. What you're saying about labourers going back and forth to Wuhan is really interesting—could the virus have spread from Italy to China, or was it the other way around? And then the extremely virulent strains really set up shop in Europe, and from there spread to North America?

      There's going to be some more very interesting forensic epidemiological work going on over the next few months and years.

      • Hard to believe the virus originated in Italy when the large breakout happened 2-3 months earlier in China than Italy.

    • It's called G-clade. And it did not happen in Italy.

  • But it's unfair to call Trump an "early mutation".

    • Narcissists don't care for name calling. It's all about themselves and not about what you think of them. The are more likely to respond with "Yes, I am" to any sort of name calling than to feel hurt about it. I bet if you called him an "early mutation" will he respond with "I'm a tremendous mutation, one that is going to make the world great again!" or something like this.

  • The more you inhibit it by hindering its spread, the more infectious it will get... apparently almost no one realizes that...

    • by ghoul ( 157158 )
      So Republican states where people refuse to wear masks should be breeding a less virulent form?
      • by sfcat ( 872532 )

        So Republican states where people refuse to wear masks should be breeding a less virulent form?

        As crazy as that sounds, yes. The more you allow the spread of a pathogen, you more you select for variants that spread more and kill less. The more you restrict spread, the more you select for the other variants which are likely more dangerous. Its like nature's version of the Chinese finger puzzle. Don't take this to mean its a good idea to just let a dangerous virus spread. But the "obvious" tactics (things that prevent spread) have a cost and you have to balance several factors to make the optimum

  • Cmon we all know that Trump sent the virus to China via infected US soldiers in November. The Chinese found out, modified it to infect people with Neanderthal genes - Europeans and South Asians and sent it back to Europe and US. The modification is why Europe and US are much worse affected than East Asia. Next time a US President wont try to use a low level infection as a way of hitting an adversary's economy because the adversary has shown they are willing to go to the wall and chnage it into a high level
  • What's fascinating to me is why this quasi-inert 80 nm diameter mote is driven to propagate as widely as possible across the planet.

    What's surreal is how this tiny total mass of particulate - a gram, two? - has spread to every corner of the globe and profoundly affected it.

    There's a lot we still don't know about the 'verse.

  • Comment removed based on user account deletion
  • This is a global problem that needs global cooperation.

    We cannot afford to leave reservoirs of this around the global so that can mutate further and come back to haunt us.

    The vaccination programme needs to be a global eradication programme better than all others. This should be true even for those that hold self interest as your primary goal in life and hold on to their American first exceptionalism.

  • It always come in pairs in mutations like that: more infectious/less deadly and vice versa.

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