27 January 2021

Did the highly transmissible British SARS-CoV-2 variant B.1.1.7 originate in one individual?



 Corona Update 27 January 2021

After discovering two immuno-compromised patients with high mutation rates and accelerated evolution, I remembered that the original publication describing the highly transmissible British SARS-CoV-2 B.1.1.7 variant, also discussed immunodeficient or immunosuppressed patients [1]. They discussed such patients for a good reason. They were puzzled with the unusual high number of mutations present in the B.1.1.7 and the fact that they did not see any precursors of the variant. Usually, there must have been a step by step accumulation of mutations. But the B.1.1.7 variant made a big jump in sequence space. They asked: What evolutionary processes or selective pressures might have given rise to lineage B.1.1.7 ?  They noted that an accumulation of many mutations in immunocompromised patients has been reported in the literature. This could also be an explanation of the origin of the B.1.1.7 variant. This is what they conclude:

"These considerations lead us to hypothesise that the unusual genetic divergence of lineage B.1.1.7 may have resulted, at least in part, from virus evolution with a chronically-infected individual. Although such infections are rare, and onward transmission from them presumably even rarer, they are not improbable given the ongoing large number of new infections.

Although we speculate here that chronic infection played a role in the origins of the B.1.1.7 variant, this remains a hypothesis and we cannot yet infer the precise nature of this event."

If this is true, then the highly transmissible British variant originated in one sick individual! One person is the source of a highly transmissible variant that conquered the world and caused severe lock-downs all over the world. Some talk even about a second pandemic.

Knowing this, it seems urgent that these immuno-compromised patients with covid-19 once released from the hospital must be kept in quarantine for a few weeks in order to prevent the spread of a dangerous new variant.

Together with another case [2] there are possibly 4 cases of immunocompromised patients with high mutation rates. The 4th patient (supposed to be the origin of B.1.1.7) is inferred to exist, but has not been identified as far as I know.

Furthermore, if true, this shows that within-host evolution of the virus does not prevent being a better between-host transmitter. 



  1. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations,  Dec 2020.
  2. Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation, December 29, 2020


  1. Gert,

    You conclude:

    Furthermore, if true, this shows that within-host evolution of the virus does not prevent being a better between-host transmitter.

    True, but I would like to add the following. As we saw in your precedent post and in my comment there, it might be possible that SARS-CoV-2 mutates in all directions during infection of a immune compromised host. I concluded in my comment that there will probably be selection between the different viruses, as long as they infect their host (within host evolution). Following that phase, there will be one between all these mutants that is able to infect other hosts. If this variant is better than the original SARS-CoV-2 in being transmitted, it will infect lots of people and it will dominate in the population. If it is not more infective it will die out. So within-host evolution produces lots of variants, between whom there will be one that is sufficiently good in being transmitted. If it is better than the original variant in infecting people it will become a new threat.

  2. Hi Marleen,
    Yes, I agree. The within-host selection is typically short-sighted evolution. But the virus in your body must be a reasonable good between-host-transmitter, otherwise it would not be in your body in the first place!
    So, while reproducing and mutating in your body, it can become better, worse, or stay the same at transmitting to new hosts. If it becomes better at infecting new hosts it must be by accident. Because there is no selection in the body for between-host transmission (impossible). Selection in the body is for making more copies.

    Yes, the world will be populated by virus variants that are better at between-host transmission, but also they must maintain a minimal good within-host reproduction, because the virus must produce enough virus particles to have a chance that some of time escape the body.
    So, yes, I largely agree...!

    Isn't it dramatic that just one unlucky person is the cause of a whole new subpandemic? Just as the first covid-19 person in Wuhan was the cause of a new pandemic. Viruses outsmart people!

  3. Hi Marleen,
    just watched an educational video of Doctor Mike Hansen.

    he says: there are different ways how a virus can increase its infectivity, but the most likely way to increase infectivity is it binds better to the ACE2 receptor.

    Interesting, isn't it? I did not expect that. This would mean selection mainly in the body of the host would at the same time benefit the spread of the virus around the world... so far this is what the evidence is suggesting... I overlooked that possibility. Or do I overlook something else?

  4. Marleen, Gert

    Right, not all mutations are created equal...!

    see e.g. Thomson et al. for detecting a real culprit, ehhh 'immune evasion mutation': DOI: 10.1016/j.cell.2021.01.037

    This doesn't look good:
    "more than 90 million cases of COVID-19 have been recorded and only about 350,000 virus variants have been sequenced. "That's only 0.4%—just the tip of the iceberg," according to Snell. "This underscores the need for broad surveillance, a detailed understanding of the molecular mechanisms of the mutations, and for the development of therapies with a high barrier to resistance against variants circulating today and those that will emerge in the future." https://www.eurekalert.org/pub_releases/2021-01/cp-sdn012821.php

    That's why Hie et al. Science, 371:6526 (2021) developed a new approach to predict 'viral escape'

    The first results look promising, they say. Gert dares to disagree: he has "seen too many brilliant ideas".....Monday, January 25, 2021 at 9:58:00 AM GMT+1

  5. Harry, that is about the N439K variant. (I will investigate that one).
    But was the variant N439K predicted by Hie et al ? (language theory)
    Did they predict that it was a viral escape mutation?

    I did not find the N439K variant in a sample of 400 sequences in the NCBI database. It cannot have a very high frequency. However, I did find one close-by with a higher frequency: L452R. Has that one been predicted?
    Please check these things out for me, Harry! (you are a believer in the theory!)

    I did not comment on that N439K mutation because I see it for the first time here. So I cannot have disagreed about it.

  6. Gert,
    Hie et al suggested that a part of the spike protein called the S2 subunit is least likely to generate escape mutations. But they didn't mention N439K as far as I know.

    Accoring to DOI: 10.1016/j.cell.2021.01.037 "Immune evasion mutations
    that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S (region) " .. "N439K provides a sentinel example of immune escape"

    Hie et al recently identified new mutations that have appeared in Singapore, South Africa, and Malaysia, that they believe should be investigated for potential viral escape (these new data are not yet peer-reviewed).https://news.mit.edu/2021/model-viruses-escape-immune-0114

  7. Gert, thanks for the video.

    It confirms what we already thought. Mutation rate is around 30 mutations per genome per year with a rate of 1.12 × 10−3 mutations per site per year. That is more than 2 mutations per month. In a patient with a weakened immune system and who knows how many virus particles that reproduce and mutate themselves at lightning speed, it is surprising that there are so "few" variants. They come from different parts of the world and now, after a year of pandemic, about 5-10 variants are found that are more contagious than the original SARS-CoV-2 virus. These are, if you consider the mutation rate, not so many variants.

    It is to be expected that the virus becomes more contagious by binding better to the ACE2 receptor. The spike protein binds the ACE2 receptor to enter the cell. It hooks itself to the cell with it. As the virus becomes more contagious, it makes sense for the spike protein to mutate and become more "sticky". And isn't that exactly what happened in the variants?


    I have to read the article you sent, Hie et al. The idea of using semantics is interesting. Thanks!

  8. Marleen

    "it is surprising that there are so "few" variants."

    May be you are surprised by the fact that there are not that many 'immune evasion mutations', as is implied by the model of Hioe et al, viz. by their distinction between syntax/grammar and semantics- or sequence and function?

  9. Harry,

    I should first read the article before I can answer you. I'll let you know. Thanks for the 'hint'

  10. Harry & Marleen, thanks for your comments.

    I will blog about ALL the mutations soon....

  11. Gert
    looking forward!

    as far as I know N439K should be common to alle variants identified so far...


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