I already mentioned that argument from the “independent science article” right in the following sentences and after that I also point out that this doesn’t preclude zoonosis either.
However, how is this relevant to zoonosis? The authors of the “independent science article” say that if the latter scenario is true, then the fact that the outbreak was first detected at a market where a lot of live wild animals were sold isn’t - in and of itself - evidence for a zoonotic spillover. That may be true, but I don’t see how the latter scenario would preclude zoonosis; and again, as I pointed out before, the authors (who did the MOA analysis) that argue for the latter scenario where virus circulated long before it arrived in Wuhan also entertain zoonosis.
Furthermore, I don’t know about you but this isn’t a game to me. This isn’t a card game where if one side looses its - quote - “best trump card” that means the other side automatically wins or at the very least deserves more credence. That’s not how this works. Each hypothesis must stand on its own merit. What is the evidence for that the virus was genetically engineered? We have it’s genome and genetic engineering would leave its marks, but despite argument to the contrary, none have survived scrutiny so far. A “weaker” version of the lab leak would say that while it’s just a natural virus that was collected by lab workers who were careless and it accidentally escaped (without any artificial alteration). In this case the genome wouldn’t provide any clues, but then (just like in the former genetic engineered version of the lab leak) you would have to propose an implausibly huge conspiracy that involves a whole bunch of people internationally working together to hide the evidence. Not just the Chinese government. The larger the scope of the conspiracy, the faster they are exposed. And yet, here we are, three years later.
When you said “well-adapted”, I thought you meant that the virus was able to infect humans and spread effectively (live-on-arrival is a prerequisite of any spillover that results in a pandemic). Now it seems that the argument is that SARS-CoV-2 was seemingly TOO well-adapted, almost like it had adapted to infecting humans for a while similar to SARS-CoV of 2003 in the later phases of its respective pandemic.
Alright, red flags. One of the authors is Alina Chan who wrote the book “Viral: The Search for the Origin of COVID-19” along with Matt Ridley (who also has a known history of climate change denial). Neither of these people are actually virologists though. Secondly, this is a preprint (not peer reviewed). Not just that. It was put up all the way back in May 2020… almost three years ago by now. Surely enough for it be reviewed and published, but it wasn’t. Is there a reason for this? Sure enough, the study is very flawed. One commenter is Robert F. Garry of Tulane University (an actual virologist) who wrote an extensive breakdown of this three months ago. I will mostly summarize what he said here:
In the figure above (A). They note that SARS-CoV of 2003 (SARS-1 for short) exhibited large genetic diversity among the 11 genomes of the early to mid phase of the epidemic (blue). In contrast, the later phase there was low genetic diversity, which is comparable to the early phase of SARS-CoV-2 (SARS-2) pandemic from Dec 2019 to March 2020. The Authors interpret this data as indicating that SARS-1 underwent rapid evolutionary adaption in the early phases, and with a lower substitution rate in the later phase after it was well-adapted to humans. In contrast, SARS-2 didn’t undergo rapid adaptation and maintained low genetic variation indicating it was adapted to humans on the same level as SARS-1 in its later phase.
This conclusion is flawed. The 11 genomes (blue dots) are NOT part of the same lineage that spilled over into humans in 2003. These first eleven cases of SARS-CoV in 2003 were distributed across a wide area (from Foshan to Dongguan in the Pearl River Delta area of southern China) and time (4 months). These early cases were not linked, i.e. originating via human-to-human transmission from the same human patient zero, and they also did not sustain human-to-human transmissions (unlike in the latter phase). Other studies have already shown that SARS-1 had experienced diversification in animals before the first human cases. Thus, the high genetic diversity among these 11 isolates isn’t an indication of rapid adaptation while it was transmitting among humans. Instead, these early cases reflect multiple independent spillovers from widespread and diverse populations of SARS-1, having diverged from each other and circulated among wild animals for a long time prior. This is similarly observed in other viruses (e.g. LASV) which has experiences thousands of spillovers every year but human-to-human transmission is limited. Subsequently, these cases exhibit high genetic diversity because these come from a wild reservoir with an established diverse gene pool.
In contrast, low diversity is the result of a few lineages that are able to sustain human-to-human transmission (producing a genetic bottle-neck). This is seen in the latter phase of SARS-1 outbreak. This involved a variant that experienced a 27-nt deletion in orf 8. A physician was exposed at his hospital in Guangzhou who later traveled to Hong Kong. There he stayed at one hotel, transmitting the virus to 16 other guests, which subsequently transmitted it further among humans in Hong Kong, Toronto, Singapore and Vietnam. Eventually it infected over 8000 people in 25 countries on five continents (killing at least 774). These cases exhibited minimal genetic variability because these were all transmitted from person to person coming from one individual. This is similarly seen in Ebola outbreaks, wherein a spillover can sustain large number of human-to-human transmissions, which exhibit lower genetic diversity.
This means that using the diversity among the 11 (blue dots) genomes to calculate the substitution rate of SARS-1 during the first 3 months in 2003 is erroneous. The diversification actually happened over during a longer time period within the animal reservoir, likely over a period of years (not 3 months) starting long before to the first detected case in humans. Thus, comparing this calculated rate with the rates seen in the later phase of SARS-1 and the pandemic of SARS-2 is completely flawed. When accounting for progenitor viruses among the wild reservoir shows that the substitution rate in the genomes within the SARS-1-like clade varies up to 6-fold, with median rates of 4.0x10^-4 and 1.91x0^-3. These are actually slightly lower (not faster) than the rates observed in the SARS-2-like clade.