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Origins of Covid

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 Hardonicus 14 Sep 2021

There seems to be some mounting evidence of the circulation of Sars-Cov-2 around China and Europe in the months preceding the first official big outbreak in Wuhan (November 2019) through serological studies of old blood samples.

It got me thinking about the statistics surrounding the seeding of outbreaks. The exponential rate becomes identifiable/predictable as infection numbers increase, but what happens at the start when numbers are small?

Is it possible for an infectious virus like Sars-Cov-2 to have been in circulation at low levels for several weeks/months around both Europe and China before the outbreaks in Wuhan, Lombardy and subsequently everywhere?

Post edited at 10:38
 mondite 14 Sep 2021
In reply to Hardonicus:

> Is it possible for an infectious virus like Sars-Cov-2 to have been in circulation at low levels for several weeks/months around both Europe and China before the outbreaks in Wuhan, Lombardy and subsequently everywhere?

My guess would be, if it is true it was around prior to when it got really noticed, there was a mutation to make it more spread more easily.

That said there do seem to be some oddities around superspreaders vs others who dont seem to really pass it on.

 Hardonicus 14 Sep 2021
In reply to mondite:

Yes there was quite a focus on particular 'super spreaders' as things kicked off over here.

 Jon Read 14 Sep 2021
In reply to Hardonicus:

Weeks, possibly, particularly if it was mostly in younger age groups initially (where a rumbling epidemic may have been less 'visible' to healthcare). Months, unlikely IMHO.

If there was a significant mutation propelling transmission rate and case numbers upwards then, given the huge expansive pool of available susceptibles and potentially little competition between 'origin' and 'invading/new' strains (network structure dependent), I would expect some of those origin strains to have still been circulating when the epidemic became clearly apparent in January 2020 and to have been picked up through genomic sampling. 

Caveat: with such a mix of stochastic noise, network effects, evolution and sampling/observation biases, intuition often fails. This may include my own!

 Jon Read 14 Sep 2021
In reply to Jon Read:

Sorry, want to clarify my vague time periods. I've seen genomic evidence suggesting emergence could have happened as early as 6th October [1], and that the first cases may have been identified through epi/healthcare data in early December.

Could the first case have happened in Wuhan in October and the epidemic stuttered along in a complicated chain until it really got established in December? Yes, this is plausible.

Do I think it could have been circulating earlier than October in Wuhan? Unlikely.

Do I think it had spread to Italy and was circulating there unnoticed in September 2019 [2]? Very unlikely from a population dynamics perspective. I don't know enough about antibody testing in that paper to comment on their reliability or susceptibility to contamination.

The Health Policy Editor for the Economist has written on the origins recently: https://overmatter.substack.com/p/the-november-story

  1. https://www.sciencedirect.com/science/article/abs/pii/S1567134820301829
  2. https://journals.sagepub.com/doi/full/10.1177/0300891620974755
Post edited at 15:52
 Jon Read 14 Sep 2021
In reply to Hardonicus:

I used to spend a lot of time thinking about pandemic emergence. This was one of my favourite (theoretical) papers on it. Figure one captures some of the complexity of it.

https://www.nature.com/articles/nature02104

In reply to Hardonicus:

> ... Is it possible for an infectious virus like Sars-Cov-2 to have been in circulation at low levels for several weeks/months ... before the outbreaks in ... 

YES, if PCR testing of sewage samples (https://www.reuters.com/article/us-health-coronavirus-italy-sewage-idUKKBN23Q1J9) is to be believed, it was present in community in Northern Italy at least as early as December 2019 and possibly since September 2019 (https://www.weforum.org/agenda/2020/11/coronavirus-italy-covid-19-pandemic-europe-date-antibodies-study/

 Hardonicus 15 Sep 2021
In reply to Jon Read:

Thanks. The implication from that paper is that there must be some proximity to the natural reservoir if a virus in in low-level circulation and R0<1?

If the premise is that viral evolution lead to an increase in infectiousness resulting in a variant with R0>1, that would be a good explanation of the Wuhan explosion (I'm assuming the natural reservoir is located in China). It does not provide such a clear explanation for low-level circulation in countries e.g. Italy located a long way from the presumed reservoir does it?

Post edited at 09:53
In reply to Hardonicus:

> If the premise is that viral evolution lead to an increase in infectiousness resulting in a variant with R0>1, that would be a good explanation of the Wuhan explosion (I'm assuming the natural reservoir is located in China).

Doesn't have to be. Could be anywhere, and the change that pushed R>1 happened there.

> It does not provide such a clear explanation for low-level circulation in countries e.g. Italy located a long way from the presumed reservoir does it?

This 'reservoir' could just as well have been in Italy

 Offwidth 15 Sep 2021
In reply to Hardonicus:

Turin had strong connections with the Chinese clothing industry with common air travel in both directions.

 jkarran 15 Sep 2021
In reply to Hardonicus:

> Thanks. The implication from that paper is that there must be some proximity to the natural reservoir if a virus in in low-level circulation and R0<1?

> If the premise is that viral evolution lead to an increase in infectiousness resulting in a variant with R0>1, that would be a good explanation of the Wuhan explosion (I'm assuming the natural reservoir is located in China). It does not provide such a clear explanation for low-level circulation in countries e.g. Italy located a long way from the presumed reservoir does it?

It feels like a long time ago now so I could be misremembering but wasn't there some sort of big trade show (or perhaps just lots of business traffic between N Italian fashion houses and makers) suspected of being the link?

It seems quite possible that something which kills 1-2% of those it meets but produces unremarkable/mistakable symptoms in most could circulate unnoticed at pretty low levels for many weeks especially given a little luck. If it finds mostly young hosts to begin with it's much less dangerous (to the individual) and if some early outbreaks smoulder (transmissions=1) or pinch off completely (transmissions=0) then the epidemic phase is delayed quite significantly. R0 was IIRC estimated to be 3ish back then but it is just the average number of transmissions per infection, fine at scale but it could easily be 0, 1 or many for any individual. Early on you only need a few 1s or 0s to delay or dead-end a transmission chain and significantly delay the onset of smooth exponential growth.

If your sewage screening is sensitive enough you could potentially be picking up the signal from those early faltering stages of the spread, a handful of cases/chains. Even if it does spread smoothly with each infection generating exactly 3 more, from 1 seed infection you maybe only have seen 3300 infections after a month (7 x 4days, an handwavy estimate from infection to symptoms showing), in an average population that might kill 33, and hospitalise ~10x more which in flu season as it was could have been missed as a new problem plus it was probably still mostly circulating in a younger business traveler/skier population at that point so potentially killing far fewer. After that it gets harder to miss especially as you get into the period where red flags were being raised in Wuhan.

edit: maths!

jk

Post edited at 10:31
 magma 15 Sep 2021
 elsewhere 15 Sep 2021
In reply to Hardonicus:

HIV is thought to have jumped into humans very roughly 110 years ago and the oldest confirmed case was 60 years ago (HIV detected later in preserved blood samples). Covid may have an older history in humans than we think.

I wonder how far back and in what variants Covid can be traced in blood samples/donations.

Covid much quicker acting (infection to illness in days) than HIV so not a hundred year history in humans unless it was a very different variant.

Is there evidence/theory about if a pandemic causing virus mutation occurred after Covid entered humans? Maybe spreads very slowly to infect a small number of people but once enough people are infected here's enough mutation going on within humans for a pandemic causing mutation of a novel* virus to happen.

*no prior immunity, presumably all viruses mutate but normally lots of prior immunity from earlier variants prevent a mutation being enough for pandemic.

Or was a human pandemic capable mutation already there in the bat/other host and it just needed an unlucky bat sneeze or whatever to infect a single person? 

Unlikely that we will discover the first person with Covid as may have been an asymptomatic or mild cases that didn't get medical treatment or blood samples preserved. Blood donations are a good sample of Covid in the population, a bit biased towards healthy and public spirited so not wholly representative. 

Post edited at 13:33
 Jon Read 15 Sep 2021
In reply to elsewhere:

This is a good review of the evidence by a selection (ho ho!) of reliable evolutionary biologists:  https://www.cell.com/cell/pdf/S0092-8674(21)00991-0.pdf

 Offwidth 15 Sep 2021
In reply to elsewhere:

Infection from bats (and other animals) happens but it doesn't usually subsequently spread from human to human afterwards. That's what was so dangerous about the gain of function research carried out in Wuhan, part funded by US research money (where the US unfairly claimed they hadn't supported gain of function work, based on the highly limited semantics of their definition) . It's obvious such efforts need tighter ethics (it's already banned in the US) and was in my view criminal that such research was carried out in bio-safety level 2 (or 3) labs and not level 4. As ever, the partisan US politics around this goes nuts.

https://www.factcheck.org/2021/05/the-wuhan-lab-and-the-gain-of-function-disagreement/

 Hardonicus 15 Sep 2021
In reply to Jon Read:

No discussion of studies of historic blood samples or sewage though? The paper focusses only on Wuhan.

Post edited at 15:13
 Offwidth 15 Sep 2021
In reply to Hardonicus:

What discussion can you have? Covid was definitely in Turin from the sewer data in December 2019.

Post edited at 15:40
 elsewhere 15 Sep 2021
In reply to Offwidth:

> Infection from bats (and other animals) happens but it doesn't usually subsequently spread from human to human afterwards.

...BUT the minority that do subsequently spread from human to human represent the main way the human race is infected by new* viruses for which we have no existing immunity.

Alternatively - zootonic* transfer is main source of new & potential pandemic causing viruses.

*eg 1918 flu originated in birds (or pigs), common cold originated in birds (or camels), Ebola and HIV from simians 

Zootonic transfer vs gain of function - no idea.

That's my rudimentary understanding so quite possibly very wrong.


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