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WHO learned diverse SARSCoV2 sequences were found in Wuhan in 12/2019, suggesting 1000s were already infected.
I've wondered if the reason why the virus appeared well adapted to humans by 12/2019 was because it had evolved silently for a while
1/n https://www.cnn.com/2021/02/14/health/who-mission-china-intl/index.html
I've wondered if the reason why the virus appeared well adapted to humans by 12/2019 was because it had evolved silently for a while
1/n https://www.cnn.com/2021/02/14/health/who-mission-china-intl/index.html
This would require the original virus to be incapable of late lung infection, so that cases from early in its evolution in humans would clear the virus without the lung inflammation that causes respiratory failure and death
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But actually if you think of it, you might expect that: the first viruses in humans would replicate okay but not great since they were not adapted to humans. They would then be cleared by the immune system like other coronaviruses that cause the common cold.
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But as they adapted, they picked up the ability to replicate to higher levels or to evade the immune system better, allowing one lucky strain to become more contagious and persist long enough to cause the late-stage respiratory complications.
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We may be seeing a sequel to that now with the B.1.1.7 strain, which replicates to higher levels and appears to cause worse disease. That is B.1.1.7 continues along the same evolutionary path to adaptation to humans, but it took a while for the B.1.1.7 mutations to occur
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In protein engineering, we often observe that natural proteins are often found in a smooth part of the evolutionary landscape, so that improved variants can be found by sequential addition of single mutations.
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But after a while improvements plateau, and then you need multiple mutations to make the next improvement. Likewise SARSCoV2 was fairly stable from 12/2019 to 9/2020 when B.1.1.7 arose with 23 changes, 2 or 3 of which are likely important together.
7/n https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-About-the-Novel-SARS-CoV-2-Va
7/n https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-About-the-Novel-SARS-CoV-2-Va
So to recap this hypothesis, the granddaddy to today's SARSCoV2 appeared in Wuhan. It was harmless and gave rise to various mutant progeny, most of which were harmless as well. But one gained the ability to evade the immune system longer than its siblings. @alinachan
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This caused it to cause late-stage lung inflammation in the immunodeficient and elderly. It also became more contagious (likely if its core ability is replication to higher titers) allowing it become the dominant variant around the world after 12/2019
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If the WHO has the sequences showing diversity mentioned in the article, then it may be possible to partially reconstruct a SARSCoV2 sequence from earlier in the human infection history. This sequence would presumably replicate worse in humans because it was less adapted
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Such a hypothesis would be testable, but I don't support testing it. I think we've all had enough with coronavirus experimentation for now.
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But it does mean that there may be other coronaviruses replicating inefficiently in and being batted away by humans right now, but just haven't yet found that combination of mutations required for persistence and thus late-stage disease. Thus we need to be on the lookout.
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And my hypothesis does not change the need to figure out capture and sampling of bats by Wuhan researchers had any role in bringing SARSCoV2 to their city. That is, the hypothesis would be completely consistent with a species jump either with or without researcher assistance
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