COVID was already adapted to humans in Wuhan

Part of the reason the coronavirus has been so successful - apart from the fact that more than half of cases may be asymptomatic - is that it’s also very good at infecting us, so it spreads very efficiently. And that’s been true since the very first recorded cases in Wuhan. Alina Chan from the Broad Institute and Shing Zhan from the University of British Columbia have analysed the genetic sequences from some of the first samples collected, and compared them. They then compared that variation to the first SARS, and spotted something odd. Phil Sansom asked them what...

Alina - SARS-2 is much more similar to SARS-1 in the late phase of its epidemic. In the case of SARS-1, when it first crossed from animals into humans we could see that the virus underwent adaptation to the new host, which was humans. And this was in the early phase of the epidemic; the virus was mutating, finding adaptive mutations that could help it transmit amongst humans. But by the time it hit the late phase of the epidemic, this genetic diversity was greatly reduced. So this finding suggested that by the time we detected SARS-2 in December of 2019, it was already really optimised, or highly adept at human transmission. So we are missing this whole period where SARS-2 should have been rapidly adapting to its new host, and this raises really important questions about where did SARS-2 come from.

Phil - Shing, could you please explain genetically what it means here for the SARS-2 to be similar to the late version of SARS-1, rather than the early one? What does genetic similarity mean here?

Shing - Within roughly the first three months of each outbreak, the genome of SARS-CoV-2 had about one fourth the amount of genetic diversity that was found in SARS-CoV-1. And we did have genetic sequence data for four samples in the Wuhan night seafood market, and we compared the genome sequences recovered from those samples to the genome sequence of the Wuhan reference of SARS-CoV-2; and what we found was that they're very similar. And what that led us to think was, maybe the outbreak that was happening at the market didn't start from some nonhuman intermediate host, but instead it could have come from some people who were already infected at the time and they were doing some grocery shopping at the market.

Phil - Where were these samples actually from? Were they from bits of meat or something?

Shing - The samples were, for example, doorknobs; they had even some samples from the sewers; and they have samples from the surfaces of garbage trucks. What it looked like to us was that the sequences were just very similar to that from humans. So there was no real evidence that data that the virus came from some animal sold at the market.

Phil - Alina, was this surprising to you?

Alina - Yeah, so in the case of SARS-1, they went straight to the local market and there they found numerous species of animals that carry SARS-1-like viruses. But importantly the SARS-1-like viruses were not a hundred percent match, and that's why we're surprised here. Here in SARS-2, when you look at the samples from the market, they're all nearly virtually 100% identical to the human version. And so what that suggests is that these viruses were not from animals that were the source of the virus, but rather that they had been dropped by humans who were infected and had visited the market.

Phil - In that case, where did this actually come from then?

Alina - There are three different scenarios that are plausible. One of them is: SARS-2 would have crossed from an animal into humans a long time ago - this could be months to years - and it just circulated undetected in the human population for that amount of time, picking up adaptive mutations along the way, and then it finally broke out in Wuhan once it had reached the state of high adaptation to human transmission. The second scenario: that SARS-2 was already pre-adapted for humans while in bats on intermediate host. And the last scenario, which is the most controversial, is that SARS-2 could have resulted from lab-based scenarios. And we're not saying this to accuse anyone of malicious intent; lab accidents happen frequently. Even the first SARS has escaped from many world-class labs, multiple times. Sometimes lab accidents happen.